Wednesday, 29 February 2012

Epilepsy Drugs versus HIV Meds - a Neuropathy Problem?

One of the standard treatments for HIV-related neuropathy pain, is the taking of anti-seizure or epilepsy drugs (Gabapentin, Carbamazepin amongst others). However, by definition, everybody is also taking HIV medications. Today's article from medpagetoday.com (see link below) looks at a study which suggests possible clashes between the two types of drug - something HIV-patients really don't want to hear! The problem is that most drug-interaction sites don't show any counter-indications for the two types of drug at the moment. If you are in this situation and are at all concerned, it's probably wise to bring it to the attention of your HIV-specialist.
That said, the authors of the article itself point out the following:
'A new guideline from the American Academy of Neurology and the International League Against Epilepsy suggests careful dosing of antiepileptic drugs in HIV-infected patients since drug interactions might decrease efficacy of antiretrovirals in some cases.
Note that the evidence base for the guidelines was judged to be weak.
'


Guideline Urges Care in Mixing HIV, Seizure Drugs
By Michael Smith, North American Correspondent, MedPage Today Published: January 04, 2012

Although the evidence is weak, doctors should be aware that combining anti-HIV and anti-epileptic medications may lead to drug-on-drug interactions, according to a new guideline.

The issue is growing in importance as more and more people -- especially in the developing world -- are living with HIV as a chronic disease, according to Gretchen Birbeck, MD, of Michigan State University in East Lansing, Mich. and colleagues.

And up to 55% of people taking antiretroviral medications may need epilepsy control drugs at some point, although not for seizures in every case, Birbeck and colleagues reported online and in the Jan. 10 issue of Neurology.

But, the authors noted, there are no formal guidelines to assist physicians in making drug choices. To help fill the gap, the American Academy of Neurology and the International League Against Epilepsy convened an international panel to sift through evidence and come up with guidelines.

The bad news, the panel found, was that the data are limited; only 42 articles yielded data, most of them reporting on Class II and Class III studies. As a result, the panel's recommendations are all level C -- any effect is only "possibly" valid.

Birbeck and colleagues noted that indications for anti-epileptic drugs have expanded beyond seizures to include such conditions as peripheral neuropathy and some psychiatric disorders.

But up to 11% of HIV patients may have seizure disorders and many more will suffer some form of peripheral neuropathy, leading to "substantial" concurrent use of anti-HIV and anti-epileptic medications worldwide, they argued.

The data analysis found that some combinations may need dose adjustments:
Patients receiving phenytoin (Dilantin) may need about a 50% increase in the dosage of lopinavir/ritonavir (Kaletra) to maintain serum concentrations at the right level
Patients taking valproic acid may need a lower dose of zidovudine (AZT) to keep serum concentrations unchanged
Patients receiving atazanavir/ritonavir (Reyataz/Norvir) may require about a 50% increase in the dose of lamotrigine (Lamictal) to keep serum concentrations unchanged

On the other hand, the limited evidence suggests that:
Using atazanavir or raltegravir (Isentress) with lamotrigine may not require lamotrigine dosage adjustment
Giving raltegravir and midazolam together may not require adjusting the midazolam dosage
Using valproic acid and efavirenz (Sustiva) may not require efavirenz dosage adjustment

It also may be important to avoid enzyme-inducing anti-epileptics for people whose HIV regimens include protease inhibitors or non-nucleoside reverse transcriptase inhibitors, the panel found.

While the evidence is still weak, the panel argued, those drug classes both use the cytochrome P450 system, and pharmacokinetic interactions might lead to virologic failure, with implications for disease progression and development of resistance.

"It is important that patients know exactly which drugs they are taking and provide that information to all prescribing health care providers caring for them," Birbeck said in a statement. "Doctors may need to watch and adjust drug doses in people with HIV/AIDS who take seizure drugs."

Source reference:
Birbeck GL, et al "Evidence-based guideline: antiepileptic drug selection for people with HIV/AIDS" Neurology 2012; 78: 139–145.


http://www.medpagetoday.com/Neurology/Seizures/30489

Tuesday, 28 February 2012

Using Acupuncture to Treat Neuropathy

Today's post comes from acufinder.com (see link below) a large California-based acupuncture website, and discusses in depth, treating neuropathy by means of Chinese medicine and acupuncture. It seems to be fairly realistic about the chances of success and the information is well-researched but for many people, acupuncture has brought some relief from neuropathic symptoms, especially pain. It should perhaps be considered as an option then but as always, discuss with your doctor and do some research, especially as to which practitioner you choose - there are many quacks around on the 'alternative' circuit. (n.b. I have absolutely no reason to doubt acufinder.com)

Treating Peripheral Neuropathy with Acupuncture and Chinese Medicine
By: Diane Joswick, L.Ac., MSOM

For some people it is experienced as the uncomfortable sensation of "pins and needles" or burning pain (especially at night) of their hands or feet. Others may suffer even more extreme symptoms such as muscle wasting, paralysis, or organ or gland dysfunction.

With more than 100 types of peripheral neuropathies in existence, each with its own characteristic set of symptoms, pattern of development, and prognosis, the symptoms can vary as much as the cause. Nevertheless, Peripheral Neuropathy is a condition that can be treated with Acupuncture and Oriental Medicine.

What is Peripheral Neuropathy?

Peripheral neuropathy describes damage to the peripheral nervous system, which transmits information from the brain and spinal cord to every other part of the body.

In most cases, peripheral neuropathy is secondary to conditions including diabetes, lupus, rheumatoid arthritis, scleroderma, alcoholism, nutritional deficiencies, AIDS, or poisoning from heavy metals, chemotherapy, or various drugs.

Other causes include compression or entrapment (carpal tunnel syndrome), direct physical injury to a nerve (trauma), penetrated injuries, fractures or dislocated bones, pressure involving superficial nerves (ulna or radial) which can result from prolonged use of crutches or staying in same position, tumor, intraneural hemorrhage, exposure to cold, radiation or atherosclerosis.

It is a syndrome which includes symptoms of numbness, tingling, pricking sensations, sensitivity to touch, burning pain, and muscle weakness and atrophy of the arms and legs. The feet and legs are likely to be affected before the hands and arms.

Symptoms of peripheral neuropathy may include:

- numbness or insensitivity to pain or temperature
- a tingling, burning, or prickling sensation
- sharp, burning pain or cramps
- extreme sensitivity to touch, even a light touch
- loss of balance and coordination
- muscle weakness
- muscle wasting
- paralysis
These symptoms are often worse at night.
Many people have signs of neuropathy upon examination but have no symptoms at all.

How can acupuncture treat peripheral neuropathy?

Traditional Chinese medicine teaches that Peripheral neuropathy is due to dampness moving to the limbs, where it obstructs the flow of Qi (energy) and Blood within them. The treatment is twofold, to treat the underlying factor that is causing this dampness to accumulate and to directly facilitate the circulation of Qi and Blood in the affected area. By improving the circulation, the nerve tissues of the affected area can be nourished to repair the nerve functions and reduce pain.

Peripheral neuropathy is a symptom for many different patterns of disharmony within the body. Oriental Medicine aims to treat each individual uniquely depending on what caused the neuropathy and how it manifests.

Your acupuncturist may do an interview and ask questions about how, what, where and when you feel pain, perspire, sleep, eat, drink and exercise, to name a few. The practitioner may also feel the pulse and observing the tongue. This interview and physical examination will help create a clear picture on which your practitioners can create a treatment plan specifically for you.

In addition to acupuncture, other methods such as transcutaneous electronic nerve stimulation (TENS), which uses small amounts of electricity to block pain signals, cutaneous acupuncture, herbal and physical therapy may be combined to achieve faster results.

What is Cutaneous Acupuncture?

Cutaneous Acupuncture is the use of acupuncture needles to stimulate an area superficially by tapping to promote the smooth flow of Qi and Blood.

The Plum blossom needle and the Seven-Star needle are special tools that are composed of a small bunch of needles attached to a handle like a hammer or broom. They are often used in the treatment of peripheral neuropathy. The affected area would be lightly tapped starting at the toes or fingers and then up the legs and arms.

Plastic, disposable plum blossom needles or seven-star needles are available for treatment at home.

What Points Are Used?

In treating peripheral neuropathy, acupuncture points on the affected area are used (treating the branch) as well as points on various parts of the body to treat the person according to their particular pattern (treating the root).

Each patient is custom-treated according to his or her specific and unique diagnosis. There are many acupuncture points on the hands and feet. Often the points will be chosen by which are the most tender to obtain the best results.

What will an Acupuncture Treatment feel like?

There seems to be little sensitivity to the insertion of acupuncture needles. They are so thin that several acupuncture needles can go into the middle of a hypodermic needle. Occasionally, there is a brief moment of discomfort as the needle penetrates the skin, but once the needles are in place, most people relax and even fall asleep for the duration of the treatment.

The length, number and frequency of treatments will vary. Typical treatments last from five to 30 minutes, with the patient being treated one or two times a week. Some symptoms are relieved after the first treatment, while more severe or chronic ailments often require multiple treatments. To find an acupuncturist go to www.Acufinder.com

What Studies have been done on Acupuncture and Peripheral Neuropathy?

Studies have suggested that acupuncture and Chinese herbal medicine are effective treatments for peripheral neuropathy.

In a study of 46 diabetic patients with PN, 34 of them reported a significant improvement in their symptoms after six courses of acupuncture treatment, and only eight of them required further sessions. However, only seven of the 34 had complete relief of their symptoms.

A larger study of 250 patients with HIV-related peripheral neuropathy compared the effects of acupuncture, amitriptyline, and placebo. Participants were assigned to receive acupuncture at standardized acupuncture points or at placebo ("fake") points, or amitriptyline or a placebo. The researchers found no significant difference in pain relief between the active treatments or the placebos. The acupuncture points studied in this trial were standardized so that everyone received exactly the same treatment. Acupuncture treatments are usually designed to fit the individual, and, as the researchers concluded, individualized treatments may have a different effect.

What Lifestyle and Dietary Changes Should I Make?

Adopting healthy habits - such as maintaining optimal weight, avoiding exposure to toxins, following a physician-supervised exercise program, eating a balanced diet, correcting vitamin deficiencies, and limiting or avoiding alcohol consumption - can reduce the physical and emotional effects of peripheral neuropathy.

Consider relaxation techniques such as yoga, meditation, self-hypnosis or biofeedback. These can help you learn to control the external factors that trigger pain.

Finding the Right Acupuncture and Chinese Medicine Practitioner

Acupuncture and Chinese Medicine work! But your experience with acupuncture will depend largely on the acupuncturist and herbalist that you choose.

You want to find the right acupuncturist for you. If you like and trust your practitioner, your encounter with acupuncture will be more positive. You will also want to know about the acupuncturists training and experience and what to expect from the acupuncture treatment.

Decide in advance what your expectations are and discuss them with your acupuncturist. A chronic illness may need several months of acupuncture treatment to have a noticeable effect. If you are not happy with your progress, think about changing acupuncturists or check with your western doctor for advice about other options.

The clearer you are about who it is that is treating you and exactly what the treatment entails, the more you will be able to relax during the acupuncture session and benefit from this ancient form of health care.

https://www.acufinder.com/Acupuncture+Information/Detail/Treating+Peripheral+Neuropathy+with+Acupuncture+and+Chinese+Medicine

Monday, 27 February 2012

What Actually Causes Neuropathy?

Irrespective of whether you are HIV positive or not, there are many causes of neuropathy (peripheral or otherwise). People frequently ask why they've contracted neuropathy and it's such a complex subject that the answer can't usually be compressed enough to fit in a blog post. This article from the National Institute of Neurological Disorders and Stroke (see link below)gives a general idea of the main causes of the disease. It doesn't really explain why an HIV-positive person may have neuropathy but then again, your neuropathy may not necessarily stem from your HIV status.

What causes peripheral neuropathy?
Last updated August 10, 2011

Peripheral neuropathy may be either inherited or acquired. Causes of acquired peripheral neuropathy include physical injury (trauma) to a nerve, tumors, toxins, autoimmune responses, nutritional deficiencies, alcoholism, and vascular and metabolic disorders. Acquired peripheral neuropathies are grouped into three broad categories: those caused by systemic disease, those caused by trauma from external agents, and those caused by infections or autoimmune disorders affecting nerve tissue. One example of an acquired peripheral neuropathy is trigeminal neuralgia (also known as tic douloureux), in which damage to the trigeminal nerve (the large nerve of the head and face) causes episodic attacks of excruciating, lightning-like pain on one side of the face. In some cases, the cause is an earlier viral infection, pressure on the nerve from a tumor or swollen blood vessel, or, infrequently, multiple sclerosis. In many cases, however, a specific cause cannot be identified. Doctors usually refer to neuropathies with no known cause as idiopathic neuropathies.

Physical injury (trauma) is the most common cause of injury to a nerve. Injury or sudden trauma, such as from automobile accidents, falls, and sports-related activities, can cause nerves to be partially or completely severed, crushed, compressed, or stretched, sometimes so forcefully that they are partially or completely detached from the spinal cord. Less dramatic traumas also can cause serious nerve damage. Broken or dislocated bones can exert damaging pressure on neighboring nerves, and slipped disks between vertebrae can compress nerve fibers where they emerge from the spinal cord.

Systemic diseases — disorders that affect the entire body —often cause peripheral neuropathy. These disorders may include: Metabolic and endocrine disorders. Nerve tissues are highly vulnerable to damage from diseases that impair the body's ability to transform nutrients into energy, process waste products, or manufacture the substances that make up living tissue. Diabetes mellitus, characterized by chronically high blood glucose levels, is a leading cause of peripheral neuropathy in the United States. About 60 percent to 70 percent of people with diabetes have mild to severe forms of nervous system damage.

Kidney disorders can lead to abnormally high amounts of toxic substances in the blood that can severely damage nerve tissue. A majority of patients who require dialysis because of kidney failure develop polyneuropathy. Some liver diseases also lead to neuropathies as a result of chemical imbalances.

Hormonal imbalances can disturb normal metabolic processes and cause neuropathies. For example, an underproduction of thyroid hormones slows metabolism, leading to fluid retention and swollen tissues that can exert pressure on peripheral nerves. Overproduction of growth hormone can lead to acromegaly, a condition characterized by the abnormal enlargement of many parts of the skeleton, including the joints. Nerves running through these affected joints often become entrapped.

Vitamin deficiencies and alcoholism can cause widespread damage to nerve tissue. Vitamins E, B1, B6, B12, and niacin are essential to healthy nerve function. Thiamine deficiency, in particular, is common among people with alcoholism because they often also have poor dietary habits. Thiamine deficiency can cause a painful neuropathy of the extremities. Some researchers believe that excessive alcohol consumption may, in itself, contribute directly to nerve damage, a condition referred to as alcoholic neuropathy.

Vascular damage and blood diseases can decrease oxygen supply to the peripheral nerves and quickly lead to serious damage to or death of nerve tissues, much as a sudden lack of oxygen to the brain can cause a stroke. Diabetes frequently leads to blood vessel constriction. Various forms of vasculitis (blood vessel inflammation) frequently cause vessel walls to harden, thicken, and develop scar tissue, decreasing their diameter and impeding blood flow. This category of nerve damage, in which isolated nerves in different areas are damaged, is called mononeuropathy multiplex or multifocal mononeuropathy.

Connective tissue disorders and chronic inflammation can cause direct and indirect nerve damage. When the multiple layers of protective tissue surrounding nerves become inflamed, the inflammation can spread directly into nerve fibers. Chronic inflammation also leads to the progressive destruction of connective tissue, making nerve fibers more vulnerable to compression injuries and infections. Joints can become inflamed and swollen and entrap nerves, causing pain.

Cancers and benign tumors can infiltrate or exert damaging pressure on nerve fibers. Tumors also can arise directly from nerve tissue cells. Widespread polyneuropathy is often associated with the neurofibromatoses, genetic diseases in which multiple benign tumors grow on nerve tissue. Neuromas, benign masses of overgrown nerve tissue that can develop after any penetrating injury that severs nerve fibers, generate very intense pain signals and sometimes engulf neighboring nerves, leading to further damage and even greater pain. Neuroma formation can be one element of a more widespread neuropathic pain condition called complex regional pain syndrome or reflex sympathetic dystrophy syndrome, which can be caused by traumatic injuries or surgical trauma. Paraneoplastic syndromes, a group of rare degenerative disorders that are triggered by a person's immune system response to a cancerous tumor, also can indirectly cause widespread nerve damage.

Repetitive stress frequently leads to entrapment neuropathies, a special category of compression injury. Cumulative damage can result from repetitive, forceful, awkward activities that require flexing of any group of joints for prolonged periods. The resulting irritation may cause ligaments, tendons, and muscles to become inflamed and swollen, constricting the narrow passageways through which some nerves pass. These injuries become more frequent during pregnancy, probably because weight gain and fluid retention also constrict nerve passageways.

Toxins can also cause peripheral nerve damage. People who are exposed to heavy metals (arsenic, lead, mercury, thallium), industrial drugs, or environmental toxins frequently develop neuropathy. Certain anticancer drugs, anticonvulsants, antiviral agents, and antibiotics have side effects that can include peripheral nerve damage, thus limiting their long-term use.

Infections and autoimmune disorders can cause peripheral neuropathy. Viruses and bacteria that can attack nerve tissues include herpes varicella-zoster (shingles), Epstein-Barr virus, cytomegalovirus, and herpes simplex-members of the large family of human herpes viruses. These viruses severely damage sensory nerves, causing attacks of sharp, lightning-like pain. Postherpetic neuralgia often occurs after an attack of shingles and can be particularly painful.

The human immunodeficiency virus (HIV), which causes AIDS, also causes extensive damage to the central and peripheral nervous systems. The virus can cause several different forms of neuropathy, each strongly associated with a specific stage of active immunodeficiency disease. A rapidly progressive, painful polyneuropathy affecting the feet and hands is often the first clinically apparent sign of HIV infection.

Lyme disease, diphtheria, and leprosy are bacterial diseases characterized by extensive peripheral nerve damage. Diphtheria and leprosy are now rare in the United States, but Lyme disease is on the rise. It can cause a wide range of neuropathic disorders, including a rapidly developing, painful polyneuropathy, often within a few weeks after initial infection by a tick bite.

Viral and bacterial infections can also cause indirect nerve damage by provoking conditions referred to as autoimmune disorders, in which specialized cells and antibodies of the immune system attack the body's own tissues. These attacks typically cause destruction of the nerve's myelin sheath or axon (the long fiber that extends out from the main nerve cell body).

Some neuropathies are caused by inflammation resulting from immune system activities rather than from direct damage by infectious organisms. Inflammatory neuropathies can develop quickly or slowly, and chronic forms can exhibit a pattern of alternating remission and relapse. Acute inflammatory demyelinating neuropathy, better known as Guillain-Barré syndrome, can damage motor, sensory, and autonomic nerve fibers. Most people recover from this syndrome although severe cases can be life threatening. Chronic inflammatory demyelinating polyneuropathy (CIDP), generally less dangerous, usually damages sensory and motor nerves, leaving autonomic nerves intact. Multifocal motor neuropathy is a form of inflammatory neuropathy that affects motor nerves exclusively; it may be chronic or acute.

Inherited forms of peripheral neuropathy are caused by inborn mistakes in the genetic code or by new genetic mutations. Some genetic errors lead to mild neuropathies with symptoms that begin in early adulthood and result in little, if any, significant impairment. More severe hereditary neuropathies often appear in infancy or childhood.

The most common inherited neuropathies are a group of disorders collectively referred to as Charcot-Marie-Tooth disease. These neuropathies result from flaws in genes responsible for manufacturing neurons or the myelin sheath. Hallmarks of typical Charcot-Marie-Tooth disease include extreme weakening and wasting of muscles in the lower legs and feet, gait abnormalities, loss of tendon reflexes, and numbness in the lower limbs.

http://www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheralneuropathy.htm#183593208

Sunday, 26 February 2012

Causes of HIV-Related Pain

It may seem that the blog is being flooded with pain articles at the moment but as anybody with both HIV and neuropathy will know, putting your finger on the cause of your pain (or pains) is anything but straightforward. Today's excellent article from thewellproject.org (see link below) addresses the HIV-patient directly and explains that it's not that simple putting the correct neuropathic, or arthritic, or stomach-related or muscular, or whatever label on your pain. With a bit of luck, after reading this, you will be able to locate the source and reason for your pain before you take it to the doctor and have to explain the whole story again. It's also possible that you have more than one source of pain and it's important to know what causes what. Forewarned is forearmed and if you have a good idea of where the problem is and what's causing it, you'll help your doctor considerably to decide the appropriate tests and treatment. However, having read this, or an article like this, never go ahead and self-medicate! Drugs can very easily negatively interact with each other and it is very important that you talk everything over with your doctor before beginning any form of treatment. This may seem like a lecture but you know it makes sense!

HIV Related Pain
Updated November 2010

Pain is common in people living with HIV (HIV+ people). One study of HIV+ people found that more than 50 percent had pain. Pain can occur at all stages of HIV disease and can affect many parts of the body. Usually pain occurs more often and becomes more severe as HIV disease progresses. But each individual is different. Some people may experience a lot of pain, while others have little or none.

What Causes Pain?
HIV related pain can have many causes:

- A symptom of HIV itself
- A symptom of other illnesses or infections
- A side effect of HIV drugs

Regardless of the reason, pain should be evaluated and treated to help HIV+ people have a good quality of life.

Common Types of Pain
The first step in managing HIV related pain is identifying the type, and if possible, the cause of pain. Some common types of pain include the following:

Peripheral Neuropathy – Pain due to nerve damage, mostly in the feet and hands. It may be described as numbness, tingling, or burning. Nerve damage can be caused by HIV drugs or other medical conditions such as diabetes. The older HIV drugs that caused the most peripheral neuropathy are not commonly used today

Abdominal Pain – There are many possible causes of abdominal pain:
A side effect of some HIV drugs (for example cramps)
Infections caused by bacteria or parasites
Problems of the intestinal tract such as irritable bowels
Inflammation of the pancreas (pancreatitis) caused by some HIV drugs or by drinking alcohol.
Bladder or urinary tract infections (especially in women)
Menstrual cramps or conditions of the uterus, cervix, or ovaries

Headache – Head pain can be mild to severe, and may be described as pressure, throbbing, or a dull ache. The most common causes of mild headaches include muscle tension, flu-like illness, and HIV drug side effects. Moderate or severe headaches can be caused by sinus pressure, tooth infections, brain infections, brain tumors, bleeding in the brain, migraines, or strokes. Sometimes the cause cannot be determined.

Joint, Muscle and Bone Pain – This pain can also be mild to severe. It may be related to conditions such as arthritis, bone disease, injury, or just aging. It can also be a side effect of some HIV drugs and medications for other conditions like hepatitis or high cholesterol.

Herpes Pain – Herpes is a family of viruses common in HIV+ people. Herpes viruses stay in the body for life, going into hiding and flaring up later. The varicella-zoster herpes virus first causes chickenpox and later can cause shingles, a painful rash along nerve pathways. Herpes simplex virus types 1 and 2 cause painful blisters around the mouth (“cold sores”) or genital area. Even after a herpes sore heals, a person may still have persistent pain.

Other Types
- Painful skin rashes due to infections or HIV drug side effects
- Chest pain caused by lung infections such as TB, bacterial pneumonia or PCP pneumonia (Pneumocystis pneumonia)
- Mouth pain caused by ulcers (“canker sores”) or fungal infections like thrush
- Fibromyalgia or related chronic pain conditions
- Pain due to cancer anywhere in the body

Assessing Pain
Once the type of pain is identified, the next step is to evaluate its characteristics. The goals of pain assessment are to:

Define the severity of pain (how much it hurts): Your health care provider may ask you to assign a number to your pain, from one (very mild pain) to ten (the worst possible pain). Pictures can also describe pain. A smiling face represents little or no pain, while a crying face represents severe pain.
Describe details of your pain: Your health care provider may ask you to describe how your pain feels, for example sharp, dull, throbbing, or burning. Is it new (acute) or have you had it for a while (chronic)? Where is it located? Is it constant or does it come and go?

You may be having pain but do not want to complain. Talking about pain to your health care provider is not the same thing as complaining! Telling your health care provider exactly how you feel is the best thing you can do to find out what is wrong and get the right treatment.

Pain Management
Once the type and characteristics of pain are identified, you and your health care provider will decide how to manage or treat it. The following factors will play a role in selecting the right type of treatment for you:

- Cause, type, and severity of pain
- Whether it is short-term or long-term
- History of substance abuse
- If your pain is being caused by a medication you are taking or another illness, your health care provider will want to take care of that first. If you are still experiencing pain, there are many options for pain relief.

Non-medicinal Therapies
Pain relief without medications such as:

- Massage
- Relaxation techniques
- Physical therapy
- Acupuncture
- Heat and cold therapy
- Hypnosis
- Mental imagery or visualization

While these may be enough to relieve pain, they are often used along with pain medications.

Non-opioid Medications
Pain relief medicines that do not contain narcotics (opiates). They are available over-the-counter or by prescription. These medicines relieve mild to moderate pain related to inflammation or swelling. Some people with a history of drug addiction prefer non-opioid pain medicines such as:

- Tylenol (acetaminophen)
- Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen (for example Advil)
- COX-2 inhibitor, a type of NSAID that is less likely to cause stomach problems, for example Celebrex (celecoxib)
- Steroids, natural or manufactured hormones that reduce inflammation. Examples include prednisone and hydrocortisone

Non-opioid pain medicines can cause side effects including liver damage (Tylenol), easy bleeding (aspirin), stomach pain or damage (aspirin and other NSAIDs), and heart problems (COX-2 inhibitors).

Opioids/Narcotics
Narcotics and related drugs known as opioids are the strongest pain relievers, available only by prescription. They are used to treat moderate to severe pain.

Opioids are classified by how fast and how long they work.

Immediate release opioids – act rapidly but pain relief lasts for a shorter period of time
Sustained-released opioids – take longer to start working but pain relief lasts longer

Opioids are also classified by their strength.

Mild to moderate pain relievers (they are often mixed with non-opioid medicines to improve their action):
- Hydrocodone
- Vicodin (hydrocodone plus acetaminophen)
- Codeine
- Tylenol with codeine (acetaminophen plus codeine)
- Ultram (tramadol)
- Severe pain relievers:
- Morphine
- Fentanyl
-OxyContin (oxycodone)
- Methadone or Buprenorphine (not commonly prescribed in first-line pain reliever treatment)
Opioids can cause side effects including drowsiness, nausea, and constipation. Overdoses can slow down breathing and cause death. Opiates can lead to dependence or addiction and may be a problem for people with a history of substance use.

Topical or Local Therapies
These are medications that are injected or applied to the skin around a painful area. Examples include the local anesthetic Xylocaine (lidocaine) and capsaicin, which comes from chili peppers.

Other Therapies
There are medicines prescribed for other purposes that also have pain-relieving properties.

Anti-depressants – relieve neuropathic pain such as peripheral neuropathy. An example is Cymbalta (dulozetine).
Anti-convulsants – usually used to treat seizures, some of these drugs work for peripheral neuropathy. An example is Neurontin (gabapentin).

Determine if the Pain Treatment Works
Once you start medication or other pain treatment, your health care provider should assess your pain regularly to see if treatment is working. Sometimes pain medications can stop working over time.

What to Do if You Have Pain?
When you experience pain, it is important to know how to get fast, safe relief.

Do not ignore your pain – Pain is the body’s way of telling us something is wrong. Ignoring pain often makes matters worse and can cause more damage in the long run.
Assess your pain – When pain occurs ask yourself the following questions:
- How long have I had the pain?
- Did it happen suddenly or over time?
- Is the pain sharp or dull?
- What makes the pain worse?
- Does anything ease the pain?
- Is the pain limited to one place or does it spread out to other areas?
- Are there other symptoms (for example numbness, cough or fever)?
Notify your health care provider – Report pain to your provider without delay. Describing your pain will help find the cause and how best to treat it.
Take your pain medicine as directed – If you need pain medications, make sure you take them exactly as prescribed. Pain medications work best if they are taken at the first sign of pain. Breaking the cycle of pain means taking medications before your pain is at its worst.
Be responsible – Pain medications are very effective when taken as prescribed. Taking them incorrectly can be dangerous. Opioids are addictive, meaning you can develop physical and emotional dependence on a drug. High doses can cause breathing problems. In the worst cases, incorrect use of opioids can be fatal.
Tell your health care provider if treatment does not work – If your pain medicine is not relieving your pain, talk to your providers. You may be taking a medication that will not work for you, or you may have built a tolerance to the drugs over time. You may need to change doses or switch to a new medication.
Pain is common among HIV+ people. But it can be managed using a variety of methods. Talk to your health care provider if you are having pain. He or she can work with you to find the cause, manage the pain, and improve your quality of life.

http://www.thewellproject.org/en_US/Living_Well/Health/HIV_Pain_Mgmt.jsp

Saturday, 25 February 2012

Neurontin (Gabapentin) How effective is it for Neuropathy?

Neurontin (or its brand name Gabapentin) is one of the most widely used drugs to try to control neuropathic symptoms. It is an anti-epileptic drug generally tried just before moving onto its cousin Pregabalin (Lyrica) but results are anything but consistent and the side effects can be distressing. Pfizer, which produces both drugs, has had considerable adverse publicity to deal with because side effects can be associated with various conditions including clinical depression. That said, neurontin has worked for many people in helping to control neuropathic pain and although scientists can't explain why (the drug is apparently barely absorbed by the system) the results are indisputable. This article from conquerchiari.org (see link below) goes into detail about the drug and is worth reading before consulting with your own doctor and then making a decision as to whether you want to begin taking neurontin.

Neurontin...

Not many people are thrilled about taking medication on a daily basis, especially one with side effects. Yet for people suffering through daily, chronic pain the choices are limited. Is the relief worth the side effects? Will the drug even work? These are some of the issues that become part of daily living for many people.
The drug Neurontin - generically known as gabapentin - is one of the most widely prescribed drugs on the market. Bringing in more than $2 billion in annual revenue for Pfizer, its manufacturer, it is a high-profile drug with a bit of a storied past. Originally designed - and approved - as an anti-epilepsy drug, it has since been FDA approved to treat post-herpetic neuralgia, a painful type of neuropathic pain that some people develop after having shingles. But with billions of dollars of sales, it is clear that Neurontin is being prescribed for more uses than just those two. In fact, a large portion of Neurontin sales are from what are known as off-label uses. Once a drug is approved by the FDA, doctors are allowed to prescribe the drug not only for the approved use, but for other uses for which they think the drug might be effective.
This is an important, and necessary, part of medicine. Many drug benefits were discovered by prescribing them off-label, including the heart related benefits of aspirin. Unfortunately, as will be discussed later, this is also where Neurontin's checkered past comes into play. Pfizer (actually Parke-Davis, a division of Warner-Lambert, which Pfizer acquired) is being accused of illegally marketing Neurontin and encouraging doctors to prescribe it off-label.

What Is Neurontin?

Neurontin was designed to look like a neurotransmitter known as GABA. GABA is an important neurotransmitter, and several types of drugs, including sedatives, work by affecting how GABA attaches to other chemicals at the molecular level. In addition, the role of GABA in spinal cord injuries is thought to be important and is being investigated by spinal cord injury researchers.
What is surprising is that no one knows how Neurontin works. No one can explain how it offers pain relief or acts as an anti-convulsant. Despite looking like GABA, it does not affect how GABA attaches - or binds - in the brain, it doesn't affect how GABA is processed, and it isn't converted into GABA by the body. In addition, gabapentin does not affect dopamine or serotonin, other common neurotransmitters. The substance was also tested to see if it would bind to many different types of sites at the molecular level, but it does not. In a study involving a rat brain, the drug was found to attach to certain areas, but the connection between those sites and how the drug might work is not clear. Adding to the mystery is the fact that gabapentin itself is barely absorbed by the human body and is fairly quickly eliminated through the kidneys and urine.

Does It Work?

Despite the unknowns, there is growing evidence that Neurontin does indeed offer some level of relief for some types of neuropathic pain. Setting aside the anti-epileptic effects of the drug, Pfizer's literature on Neurontin cites two randomized, double-blind, placebo controlled studies on the use of Neurontin for managing postherpetic neuralgia. The studies involved 563 patients who were experiencing pain at least 3 months after their bout with shingles. The patients were given either Neurontin or a placebo for a several week period (dosage was ramped up to 3600mg/day). Both studies showed a significant reduction in reported pain throughout the treatment for those receiving the drug. In fact, around 30% of the participants receiving the drug reported a 50% or greater improvement in their pain.
However, there are many types of pain, and is postherpetic neuralgia similar to SM pain? Fortunately, Neurontin has also been shown to help pain associated with spinal cord injuries. In a study published in 2003 (Spine 28(4):341-6), 31 patients with neuropathic pain due to spinal cord injury were given Neurontin over an 8 week period. The patients were divided into two groups based on whether they had been experiencing pain for less than or more than 6 months. Despite the fact that they tried other types of pain medicines to no avail, Neurontin did reduce the pain for both groups. On a scale of 0-10, the average pain score for the less than 6 month group dropped from 7.3 to 3 over the course of the treatment. While the other group also responded to the drug, the average score only dropped from 7.6 to 5. So while this study shows Neurontin can provide relief for SCI related pain, getting started early on the drug may be important.
Another study demonstrating the effects of Neurontin on a wide variety of neuropathic pain was published in the journal Pain in 2002 (Pain 99(3):557-66). This double-blind, randomized, placebo controlled study looked at over 300 people suffering from neuropathic pain due to a number of different causes. Over an 8-week period, the participants either received Neurontin or a placebo. The results showed a significant difference in the pain relief between the group receiving the drug and the placebo group.
Of special interest to the CM/SM community is growing evidence which shows that Neurontin can reduce the brutal consequences of allodynia. This type of pain - feeling pain from things that shouldn't be painful - can be especially limiting and difficult to deal with. In well established rat models, gabapentin - along with other, similar drugs - has been shown to dramatically reduce allodynia. As more and more rigorous studies are published showing the beneficial effects of Neurontin, attention will likely turn to how it works. And once the exact mechanisms are understood, it should become clearer who the drug can benefit the most.

What About Side Effects?

A drug's effectiveness is only half the equation. In order to be useful, any side effects caused by the drug must be minor enough to be tolerated or the drug is essentially worthless. Narcotics are powerful pain relievers, but also have very strong side effects. In narcotic studies, it is not unusual for more than 20% of participants to drop out because of side effects. In addition, drug tolerance and addiction pose even bigger challenges to the effective use of a narcotics for pain relief. What are the side effects of Neurontin like, are they as bad as narcotics'?
In a postherpetic neuralgia study cited by Pfizer, the most common side effects of Neurontin were sleepiness, dizziness, numbness, and bruising. Twenty-eight percent of participants reported experiencing dizziness and 21% sleepiness. Because of this, more than 3% of participants experienced accidental injuries versus just 1% of the control group. In addition to the most common effects, there are a wide range of less common side effects which nonetheless did not occur in the placebo group. These range from dry mouth to rashes to blurred vision to stomach problems to cognitive impairment.
Similar side effects are listed in other published gabapentin studies but are usually characterized as mild to moderate. Overall, the drug is considered very safe with few and infrequent serious medical side effects. One reason for this is that the body metabolizes very little of the drug itself and the drug doesn't stay in the body for very long. Addiction to the drug has not been studied adequately to make a determination if it is a problem.
Anecdotally, people contacted by this publication with experience taking Neurontin present a mixed view. Most encountered some side effects with sleepiness and cognitive impairment being most prominent. Several people stopped taking the drug because of the side effects, but one person who stayed on it for awhile became used to the side effects and after a period of time was able to function normally.
As mentioned in Community News, Pfizer is seeking approval for a follow-on drug which is intended to help control neuropathic pain with even less side effects than Neurontin.

Things To Be Aware Of

As with any drug, there are a number of precautions, or things to be aware of, when either taking or considering Neurontin:

Naproxen - Studies show that when gabapentin is taken with Naproxen (the active ingredient in Alleve), the amount of gabapentin absorbed is 12%-15% higher than usual.

Morphine - A study showed that morphine given 2 hours before gabapentin increased the absorption of gabapentin by 44%. The morphine absorption was not effected.

Antacids - Maalox has been shown to inhibit the action of gabapentin. It is recommended that gabapentin be taken at least 2 hours after Maalox.

Oral Contraceptives - Studies have shown that gabapentin does not interfere with the effectiveness of two common oral contraceptives.

Pregnancy - Rat studies have shown that gabapentin is toxic to fetuses. Effects were seen at dosage levels of 1-4 times the daily maximum dose of 3600 mg/day. No effect was seen at 1/2 the daily dose level (for people). In addition, when rats were given the drug before and during mating, there were adverse effects at doses 1-5 times the daily human dose. There are no studies involving pregnant women.

Nursing - Gabapentin is secreted into breast milk. The effects on a nursing baby are unknown.

Pediatric - The drug is not FDA approved as a pain treatment for children under 12. In a study of children between the age of 3-12 (with epilepsy), behavioral problems were seen, including hostility, aggression, and other emotional problems

Dosage - People with kidney problems may need to take a lower dose of the drug

Please note the above is not an inclusive list. More information about precautions can be found from the manufacturer or a doctor or pharmacist.

The Controversy

Despite it's apparent effectiveness, Neurontin is a controversial drug. The controversy stems from a highly publicized whistleblower lawsuit filed by a former employee, David Franklin, Ph.D.
Franklin - who has since been joined by the Justice Department - claims that Parke-Davis (later acquired by Pfizer in a merger with Warner Lambert) broke the law by marketing Neurontin for off-label uses. While such prescriptions are allowed, drug companies are not allowed to promote them.
Franklin was employed as a medical liaison, someone with scientific credentials who is supposed to answer doctor's medical and technical questions. Franklin claims that there was a company wide campaign to push Neurontin for uses - such as treating bipolar disorder - for which there was no evidence that the drug worked. In addition, he claims that doctors were paid money to put their names on articles they didn't write, and were often flown to vacation-style getaway locations for 'education' sessions.
NBC's Dateline show conducted a year long investigation and aired an extensive interview with Franklin. Dateline was able to obtain internal Parke-Davis documents which they claim show a systematic push to promote Neurontin for off-label uses. During the interview, recorded voice messages were played that certainly seem incriminating. Franklin claims that the evidence shows that the company put sales ahead of good medicine.
Pfizer denies the claim and it should be pointed out that as a whistleblower, Franklin stands to gain financially from a successful lawsuit. Pfizer did not return a request to comment on any aspect of Neurontin, the controversy, or their new drug application.

The Bottom Line

Despite the controversy, Neurontin does appear to be effective in helping some people deal with neuropathic pain. The side effects are not severe from a medical perspective, but can still be too much from a patient's perspective. Like so many aspects of Daily Living for people with Chiari and syringomyelia, there are no easy answers when it comes to Neurontin. For some it may be a blessing, for some yet another waste of time, but for everyone, it is at least worth knowing about.

Sources:
Pfizer, Inc. web site and drug literature
Serpell, MG. Gabapentin in neuropathic pain syndromes. Pain Oct, 2002 99(3): 557-66.
Ahn SH et.al. Gabapentin effect on neuropathic pain compared among patients with spinal cord injury and different duration of symptoms. Spine Feb, 15 2003 28(4): 341-6.
FDA web site
MSNBC web site, Dateline interview with David Franklin
Theo Emery (AP), Whistleblower's lawsuit could shake up the drug industry, 8/9/03


http://www.conquerchiari.org/subs%20only/Volume%201/Issue%205/Daily%20Living%20%20Neurontin%201(5).asp

Friday, 24 February 2012

Living with HIV and Neuropathy

Today's post is a moving five minute video from a man describing his experience of being tested and subsequently living with HIV and Neuropathy. It will be uncomfortably recognisable to many and is also a reminder that not everybody can just take the meds and live a 'normal' life. (See Transcript and link below)



Transcript

Michael Silvas: I am Michael Silvas and this year I turned 50. I became positive in 1993 while I was diagnosed positive with AIDS. I should have known and should have been tested prior to that denial so weird. The very first person who gave me, who -- I should've known I had AIDS was my dentist. And it was another person I worked with, referred patients with and all that, and he was very good. He had said to me, he said, "Michael, when was the last time, you know, you had an HIV Test?" that should've told me, I'd better get down there and get an HIV test.The first symptoms that I was feeling with unaware for AIDS and maybe someone else can relate to is the reason why I am going through this detail. I would come home -- I was teaching Inclusive Marketing at the time with IBM, and my feet --I remember on Fridays I would come home and my feet would just be killing me and I thought it was the wing-tip shoes because with IBM we wore -- back in my day, we wore dark suits and wing-tipped shoes and etc. And I thought it was me being on my feet all the time, I thought it was the style of the shoes. I never-never would have thought that it was actually a disease or a medical condition.And I didn't even; in fact I had already been diagnosed with AIDS for several years, before I knew that it was actually the medical condition that that there was a thing called Neuropathy. When I was tested, I went down with a friend of mine who I knew was going to get it, you know who had it, I just knew he had it and he has been talking about getting tested but he wouldn't go because he was scared. And so I said -- well, you know, he asked me to go with him and I said, "Sure, I'll go with you" because I wasn't worried that I was going to come out, you know, positive.And now it shocked me! I don't advice anyone to do that, you know. If you really don't want to share your information with a friend, don't go with a friend. It is a big -- it does change your life in a dramatic way and you might not -- you might have a different perspective once you get the diagnosis as to who you want to share it with. I remember getting back in the car and just expecting that they were going to be positive, and then you know I saw that he didn't have a packet and I did and then I had to explain it to him. It just -- I don't know! It was like kind of takes your breath away. When I get asked, you know, how were you infected? It has to be sex!And I felt like I was at the top of my game when I became very sick one week and all of a sudden my stomach started swelling up and getting bigger and bigger. And I started losing controls of my bowels, the lack of better words shitting all over myself and vomiting and vomiting. I went in the emergency room and I remember we called my therapist because I had already started going -- I had already been diagnosed with AIDS but I hadn't been sick and so I started therapy, Psych-therapy. And so I called her as when I was going in the emergency room, she was in there with me. And I remember so clearly that I was there dying on the bed in the emergency room and no one would get near me, no one would -- everyone was scared to touch me.My Doctor at the time, who was an Immunologist was on vacation and his backup never showed, never came. The nurses didn't want to touch me, no one, no doctor wanted to attend me, even with my therapist there advocating for me. What they ended up doing was giving me a shot of a Demerol and sending me home without any examination, without anything -- seeing my stomach just ended, you know, big. Kind of like you see the African babies with the swollen babies when they're starving, it was like that. And so pretty much I went home to die. But at least I wasn't in as much pain for at the moment.I was living -- and it is so funny because I was living in a complex who accepted rental assistance, I had broken out with Shingles really bad. And I understand that normally shingles you get only on one side, but I had it on both sides and it looked like I had been whipped. You know all across my back and all of my legs; it just looked like they've been whipped with sores. I mean it was awful. And I had decided that I was going to not be ashamed, it was part of me trying to cope with my diagnosis and I wore shorts and that was a mistake.I came through -- as I was coming through the complex and walking by the pool, people noticed that there was something, you know, wrong with my legs. And they became aware and they started talking and then they started snubbing me and then they started harassing me and they would do things to me to -- to force me to move.Female Speaker: Wow!Michael Silvas: I take two in the morning, two in the morning and two at night!Female Speaker: And that's also for HIV?Michael Silvas: Yeah! I have to take these together. Along with -- when I take both, I have to take Tenofovir which is a booster. This is a really -- considered a really wonderful break through. For the first time with this medication I had the first undetectable test however it didn't last long.Female Speaker: Okay!Michael Silvas: And now these really aren't really functioning -- I think that if you're considering going into any type of relationship, in fact I do know of people who were in going into a relationship before having sex, especially unprotected sex, they test. And that's almost a way of life now and it should be everyone's way of life. You don't hear enough about that.


http://www.freehealthvideos.net/8837/living-with-hiv-michael-silvas.html

Thursday, 23 February 2012

What Pain Is - PART 2

Today's post is PART TWO of a two part article about pain: the introduction below is the same as that for yesterday.

I very seldom recommend an article, or advise people strongly to read it. I generally let the reader make up his or her mind if the subject interests them or not. However, today's and tomorrow's two-part post from the National Institute of Neurological Disorders and Stroke (see link below) seems to me to be extremely useful for most people living with HIV and/or Neuropathy. It was written in 2001 but as you will see, very little has changed since then (an indictment of how far we've advanced treatment of our disease!)
Sooner or later, it is possible that you will experience some HIV-related complaint which gives you pain. If it's not HIV-related then it's very helpful to be able to identify what it is. HIV-patients are constantly excluding possiblities before getting to the source of their problem. That applies even more to people with neuropathy. It is so complex; with so many causes and forms, that getting to the root of your pain problem is liking walking through a minefield.
This article provides a sort of easily-understandable breakdown of the various forms of pain and how they're treated (including 'alternative' treatments). It's long (had to be split up over two days) but absolutely worth reading, even if you're not in pain yourself. It will help to calm the inbuilt hypochondria that people with HIV acquire through experience and enable them to rule out many of their worries.


Pain: Hope Through Research
Prepared by:
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892


What is the Role of Age and Gender in Pain?
Gender and Pain

It is now widely believed that pain affects men and women differently. While the sex hormones estrogen and testosterone certainly play a role in this phenomenon, psychology and culture, too, may account at least in part for differences in how men and women receive pain signals. For example, young children may learn to respond to pain based on how they are treated when they experience pain. Some children may be cuddled and comforted, while others may be encouraged to tough it out and to dismiss their pain.

Many investigators are turning their attention to the study of gender differences and pain. Women, many experts now agree, recover more quickly from pain, seek help more quickly for their pain, and are less likely to allow pain to control their lives. They also are more likely to marshal a variety of resources-coping skills, support, and distraction-with which to deal with their pain.

Research in this area is yielding fascinating results. For example, male experimental animals injected with estrogen, a female sex hormone, appear to have a lower tolerance for pain-that is, the addition of estrogen appears to lower the pain threshold. Similarly, the presence of testosterone, a male hormone, appears to elevate tolerance for pain in female mice: the animals are simply able to withstand pain better. Female mice deprived of estrogen during experiments react to stress similarly to male animals. Estrogen, therefore, may act as a sort of pain switch, turning on the ability to recognize pain.

Investigators know that males and females both have strong natural pain-killing systems, but these systems operate differently. For example, a class of painkillers called kappa-opioids is named after one of several opioid receptors to which they bind, the kappa-opioid receptor, and they include the compounds nalbuphine (Nubain®) and butorphanol (Stadol®). Research suggests that kappa-opioids provide better pain relief in women.

Though not prescribed widely, kappa-opioids are currently used for relief of labor pain and in general work best for short-term pain. Investigators are not certain why kappa-opioids work better in women than men. Is it because a woman's estrogen makes them work, or because a man's testosterone prevents them from working? Or is there another explanation, such as differences between men and women in their perception of pain? Continued research may result in a better understanding of how pain affects women differently from men, enabling new and better pain medications to be designed with gender in mind.

Pain in Aging and Pediatric Populations: Special Needs and Concerns

Pain is the number one complaint of older Americans, and one in five older Americans takes a painkiller regularly. In 1998, the American Geriatrics Society (AGS) issued guidelines* for the management of pain in older people. The AGS panel addressed the incorporation of several non-drug approaches in patients' treatment plans, including exercise. AGS panel members recommend that, whenever possible, patients use alternatives to aspirin, ibuprofen, and other NSAIDs because of the drugs' side effects, including stomach irritation and gastrointestinal bleeding. For older adults, acetaminophen is the first-line treatment for mild-to-moderate pain, according to the guidelines. More serious chronic pain conditions may require opioid drugs (narcotics), including codeine or morphine, for relief of pain.

Pain in younger patients also requires special attention, particularly because young children are not always able to describe the degree of pain they are experiencing. Although treating pain in pediatric patients poses a special challenge to physicians and parents alike, pediatric patients should never be undertreated. Recently, special tools for measuring pain in children have been developed that, when combined with cues used by parents, help physicians select the most effective treatments.

Nonsteroidal agents, and especially acetaminophen, are most often prescribed for control of pain in children. In the case of severe pain or pain following surgery, acetaminophen may be combined with codeine.

* Journal of the American Geriatrics Society (1998; 46:635-651).

A Pain Primer: What Do We Know About Pain?

We may experience pain as a prick, tingle, sting, burn, or ache. Receptors on the skin trigger a series of events, beginning with an electrical impulse that travels from the skin to the spinal cord. The spinal cord acts as a sort of relay center where the pain signal can be blocked, enhanced, or otherwise modified before it is relayed to the brain. One area of the spinal cord in particular, called the dorsal horn (see section on Spine Basics in the Appendix), is important in the reception of pain signals.

The most common destination in the brain for pain signals is the thalamus and from there to the cortex, the headquarters for complex thoughts. The thalamus also serves as the brain's storage area for images of the body and plays a key role in relaying messages between the brain and various parts of the body. In people who undergo an amputation, the representation of the amputated limb is stored in the thalamus. (For a discussion of the thalamus and its role in this phenomenon, called phantom pain, see section on Phantom Pain in the Appendix.)

Pain is a complicated process that involves an intricate interplay between a number of important chemicals found naturally in the brain and spinal cord. In general, these chemicals, called neurotransmitters, transmit nerve impulses from one cell to another.

There are many different neurotransmitters in the human body; some play a role in human disease and, in the case of pain, act in various combinations to produce painful sensations in the body. Some chemicals govern mild pain sensations; others control intense or severe pain.

The body's chemicals act in the transmission of pain messages by stimulating neurotransmitter receptors found on the surface of cells; each receptor has a corresponding neurotransmitter. Receptors function much like gates or ports and enable pain messages to pass through and on to neighboring cells. One brain chemical of special interest to neuroscientists is glutamate. During experiments, mice with blocked glutamate receptors show a reduction in their responses to pain. Other important receptors in pain transmission are opiate-like receptors. Morphine and other opioid drugs work by locking on to these opioid receptors, switching on pain-inhibiting pathways or circuits, and thereby blocking pain.

Another type of receptor that responds to painful stimuli is called a nociceptor. Nociceptors are thin nerve fibers in the skin, muscle, and other body tissues, that, when stimulated, carry pain signals to the spinal cord and brain. Normally, nociceptors only respond to strong stimuli such as a pinch. However, when tissues become injured or inflamed, as with a sunburn or infection, they release chemicals that make nociceptors much more sensitive and cause them to transmit pain signals in response to even gentle stimuli such as breeze or a caress. This condition is called allodynia -a state in which pain is produced by innocuous stimuli.

The body's natural painkillers may yet prove to be the most promising pain relievers, pointing to one of the most important new avenues in drug development. The brain may signal the release of painkillers found in the spinal cord, including serotonin, norepinephrine, and opioid-like chemicals. Many pharmaceutical companies are working to synthesize these substances in laboratories as future medications.

Endorphins and enkephalins are other natural painkillers. Endorphins may be responsible for the "feel good" effects experienced by many people after rigorous exercise; they are also implicated in the pleasurable effects of smoking.

Similarly, peptides, compounds that make up proteins in the body, play a role in pain responses. Mice bred experimentally to lack a gene for two peptides called tachykinins-neurokinin A and substance P-have a reduced response to severe pain. When exposed to mild pain, these mice react in the same way as mice that carry the missing gene. But when exposed to more severe pain, the mice exhibit a reduced pain response. This suggests that the two peptides are involved in the production of pain sensations, especially moderate-to-severe pain. Continued research on tachykinins, conducted with support from the NINDS, may pave the way for drugs tailored to treat different severities of pain.

Scientists are working to develop potent pain-killing drugs that act on receptors for the chemical acetylcholine. For example, a type of frog native to Ecuador has been found to have a chemical in its skin called epibatidine, derived from the frog's scientific name, Epipedobates tricolor. Although highly toxic, epibatidine is a potent analgesic and, surprisingly, resembles the chemical nicotine found in cigarettes. Also under development are other less toxic compounds that act on acetylcholine receptors and may prove to be more potent than morphine but without its addictive properties.

The idea of using receptors as gateways for pain drugs is a novel idea, supported by experiments involving substance P. Investigators have been able to isolate a tiny population of neurons, located in the spinal cord, that together form a major portion of the pathway responsible for carrying persistent pain signals to the brain. When animals were given injections of a lethal cocktail containing substance P linked to the chemical saporin, this group of cells, whose sole function is to communicate pain, were killed. Receptors for substance P served as a portal or point of entry for the compound. Within days of the injections, the targeted neurons, located in the outer layer of the spinal cord along its entire length, absorbed the compound and were neutralized. The animals' behavior was completely normal; they no longer exhibited signs of pain following injury or had an exaggerated pain response. Importantly, the animals still responded to acute, that is, normal, pain. This is a critical finding as it is important to retain the body's ability to detect potentially injurious stimuli. The protective, early warning signal that pain provides is essential for normal functioning. If this work can be translated clinically, humans might be able to benefit from similar compounds introduced, for example, through lumbar (spinal) puncture.

Another promising area of research using the body's natural pain-killing abilities is the transplantation of chromaffin cells into the spinal cords of animals bred experimentally to develop arthritis. Chromaffin cells produce several of the body's pain-killing substances and are part of the adrenal medulla, which sits on top of the kidney. Within a week or so, rats receiving these transplants cease to exhibit telltale signs of pain. Scientists, working with support from the NINDS, believe the transplants help the animals recover from pain-related cellular damage. Extensive animal studies will be required to learn if this technique might be of value to humans with severe pain.

One way to control pain outside of the brain, that is, peripherally, is by inhibiting hormones called prostaglandins. Prostaglandins stimulate nerves at the site of injury and cause inflammation and fever. Certain drugs, including NSAIDs, act against such hormones by blocking the enzyme that is required for their synthesis.

Blood vessel walls stretch or dilate during a migraine attack and it is thought that serotonin plays a complicated role in this process. For example, before a migraine headache, serotonin levels fall. Drugs for migraine include the triptans: sumatriptan (Imitrix®), naratriptan (Amerge®), and zolmitriptan (Zomig®). They are called serotonin agonists because they mimic the action of endogenous (natural) serotonin and bind to specific subtypes of serotonin receptors.

Ongoing pain research, much of it supported by the NINDS, continues to reveal at an unprecedented pace fascinating insights into how genetics, the immune system, and the skin contribute to pain responses.

The explosion of knowledge about human genetics is helping scientists who work in the field of drug development. We know, for example, that the pain-killing properties of codeine rely heavily on a liver enzyme, CYP2D6, which helps convert codeine into morphine. A small number of people genetically lack the enzyme CYP2D6; when given codeine, these individuals do not get pain relief. CYP2D6 also helps break down certain other drugs. People who genetically lack CYP2D6 may not be able to cleanse their systems of these drugs and may be vulnerable to drug toxicity. CYP2D6 is currently under investigation for its role in pain.

In his research, the late John C. Liebeskind, a renowned pain expert and a professor of psychology at UCLA, found that pain can kill by delaying healing and causing cancer to spread. In his pioneering research on the immune system and pain, Dr. Liebeskind studied the effects of stress-such as surgery-on the immune system and in particular on cells called natural killer or NK cells. These cells are thought to help protect the body against tumors. In one study conducted with rats, Dr. Liebeskind found that, following experimental surgery, NK cell activity was suppressed, causing the cancer to spread more rapidly. When the animals were treated with morphine, however, they were able to avoid this reaction to stress.

The link between the nervous and immune systems is an important one. Cytokines, a type of protein found in the nervous system, are also part of the body's immune system, the body's shield for fighting off disease. Cytokines can trigger pain by promoting inflammation, even in the absence of injury or damage. Certain types of cytokines have been linked to nervous system injury. After trauma, cytokine levels rise in the brain and spinal cord and at the site in the peripheral nervous system where the injury occurred. Improvements in our understanding of the precise role of cytokines in producing pain, especially pain resulting from injury, may lead to new classes of drugs that can block the action of these substances.

What is the Future of Pain Research?

In the forefront of pain research are scientists supported by the National Institutes of Health (NIH), including the NINDS. Other institutes at NIH that support pain research include the National Institute of Dental and Craniofacial Research, the National Cancer Institute, the National Institute of Nursing Research, the National Institute on Drug Abuse, and the National Institute of Mental Health. Developing better pain treatments is the primary goal of all pain research being conducted by these institutes.

Some pain medications dull the patient's perception of pain. Morphine is one such drug. It works through the body's natural pain-killing machinery, preventing pain messages from reaching the brain. Scientists are working toward the development of a morphine-like drug that will have the pain-deadening qualities of morphine but without the drug's negative side effects, such as sedation and the potential for addiction. Patients receiving morphine also face the problem of morphine tolerance, meaning that over time they require higher doses of the drug to achieve the same pain relief. Studies have identified factors that contribute to the development of tolerance; continued progress in this line of research should eventually allow patients to take lower doses of morphine.

One objective of investigators working to develop the future generation of pain medications is to take full advantage of the body's pain "switching center" by formulating compounds that will prevent pain signals from being amplified or stop them altogether. Blocking or interrupting pain signals, especially when there is no injury or trauma to tissue, is an important goal in the development of pain medications. An increased understanding of the basic mechanisms of pain will have profound implications for the development of future medicines. The following areas of research are bringing us closer to an ideal pain drug.

Systems and Imaging: The idea of mapping cognitive functions to precise areas of the brain dates back to phrenology, the now archaic practice of studying bumps on the head. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and other imaging technologies offer a vivid picture of what is happening in the brain as it processes pain. Using imaging, investigators can now see that pain activates at least three or four key areas of the brain's cortex-the layer of tissue that covers the brain. Interestingly, when patients undergo hypnosis so that the unpleasantness of a painful stimulus is not experienced, activity in some, but not all, brain areas is reduced. This emphasizes that the experience of pain involves a strong emotional component as well as the sensory experience, namely the intensity of the stimulus.

Channels: The frontier in the search for new drug targets is represented by channels. Channels are gate-like passages found along the membranes of cells that allow electrically charged chemical particles called ions to pass into the cells. Ion channels are important for transmitting signals through the nerve's membrane. The possibility now exists for developing new classes of drugs, including pain cocktails that would act at the site of channel activity.

Trophic Factors: A class of "rescuer" or "restorer" drugs may emerge from our growing knowledge of trophic factors, natural chemical substances found in the human body that affect the survival and function of cells. Trophic factors also promote cell death, but little is known about how something beneficial can become harmful. Investigators have observed that an over-accumulation of certain trophic factors in the nerve cells of animals results in heightened pain sensitivity, and that some receptors found on cells respond to trophic factors and interact with each other. These receptors may provide targets for new pain therapies.

Molecular Genetics: Certain genetic mutations can change pain sensitivity and behavioral responses to pain. People born genetically insensate to pain-that is, individuals who cannot feel pain-have a mutation in part of a gene that plays a role in cell survival. Using "knockout" animal models-animals genetically engineered to lack a certain gene-scientists are able to visualize how mutations in genes cause animals to become anxious, make noise, rear, freeze, or become hypervigilant. These genetic mutations cause a disruption or alteration in the processing of pain information as it leaves the spinal cord and travels to the brain. Knockout animals can be used to complement efforts aimed at developing new drugs.

Plasticity: Following injury, the nervous system undergoes a tremendous reorganization. This phenomenon is known as plasticity. For example, the spinal cord is "rewired" following trauma as nerve cell axons make new contacts, a phenomenon known as "sprouting." This in turn disrupts the cells' supply of trophic factors. Scientists can now identify and study the changes that occur during the processing of pain. For example, using a technique called polymerase chain reaction, abbreviated PCR, scientists can study the genes that are induced by injury and persistent pain. There is evidence that the proteins that are ultimately synthesized by these genes may be targets for new therapies. The dramatic changes that occur with injury and persistent pain underscore that chronic pain should be considered a disease of the nervous system, not just prolonged acute pain or a symptom of an injury. Thus, scientists hope that therapies directed at preventing the long-term changes that occur in the nervous system will prevent the development of chronic pain conditions.

Neurotransmitters: Just as mutations in genes may affect behavior, they may also affect a number of neurotransmitters involved in the control of pain. Using sophisticated imaging technologies, investigators can now visualize what is happening chemically in the spinal cord. From this work, new therapies may emerge, therapies that can help reduce or obliterate severe or chronic pain.

Hope for the Future
Thousands of years ago, ancient peoples attributed pain to spirits and treated it with mysticism and incantations. Over the centuries, science has provided us with a remarkable ability to understand and control pain with medications, surgery, and other treatments. Today, scientists understand a great deal about the causes and mechanisms of pain, and research has produced dramatic improvements in the diagnosis and treatment of a number of painful disorders. For people who fight every day against the limitations imposed by pain, the work of NINDS-supported scientists holds the promise of an even greater understanding of pain in the coming years. Their research offers a powerful weapon in the battle to prolong and improve the lives of people with pain: hope.

Appendix

Spine Basics: The Vertebrae, Discs, and Spinal Cord

Stacked on top of one another in the spine are more than 30 bones, the vertebrae, which together form the spine. They are divided into four regions:

the seven cervical or neck vertebrae (labeled C1-C7),
the 12 thoracic or upper back vertebrae (labeled T1-T12),
the five lumbar vertebrae (labeled L1-L5), which we know as the lower back, and
the sacrum and coccyx, a group of bones fused together at the base of the spine.
The vertebrae are linked by ligaments, tendons, and muscles. Back pain can occur when, for example, someone lifts something too heavy, causing a sprain, pull, strain, or spasm in one of these muscles or ligaments in the back.

Between the vertebrae are round, spongy pads of cartilage called discs that act much like shock absorbers. In many cases, degeneration or pressure from overexertion can cause a disc to shift or protrude and bulge, causing pressure on a nerve and resultant pain. When this happens, the condition is called a slipped, bulging, herniated, or ruptured disc, and it sometimes results in permanent nerve damage.

The column-like spinal cord is divided into segments similar to the corresponding vertebrae: cervical, thoracic, lumbar, sacral, and coccygeal. The cord also has nerve roots and rootlets which form branch-like appendages leading from its ventral side (that is, the front of the body) and from its dorsal side (that is, the back of the body). Along the dorsal root are the cells of the dorsal root ganglia, which are critical in the transmission of "pain" messages from the cord to the brain. It is here where injury, damage, and trauma become pain.

The Nervous Systems

The central nervous system (CNS) refers to the brain and spinal cord together. The peripheral nervous system refers to the cervical, thoracic, lumbar, and sacral nerve trunks leading away from the spine to the limbs. Messages related to function (such as movement) or dysfunction (such as pain) travel from the brain to the spinal cord and from there to other regions in the body and back to the brain again. The autonomic nervous system controls involuntary functions in the body, like perspiration, blood pressure, heart rate, or heart beat. It is divided into the sympathetic and parasympathetic nervous systems. The sympathetic and parasympathetic nervous systems have links to important organs and systems in the body; for example, the sympathetic nervous system controls the heart, blood vessels, and respiratory system, while the parasympathetic nervous system controls our ability to sleep, eat, and digest food.

The peripheral nervous system also includes 12 pairs of cranial nerves located on the underside of the brain. Most relay messages of a sensory nature. They include the olfactory (I), optic (II), oculomotor (III), trochlear (IV), trigeminal (V), abducens (VI), facial (VII), vestibulocochlear (VIII), glossopharyngeal (IX), vagus (X), accessory (XI), and hypoglossal (XII) nerves. Neuralgia, as in trigeminal neuralgia, is a term that refers to pain that arises from abnormal activity of a nerve trunk or its branches. The type and severity of pain associated with neuralgia vary widely.

Phantom Pain: How Does the Brain Feel?

Sometimes, when a limb is removed during an amputation, an individual will continue to have an internal sense of the lost limb. This phenomenon is known as phantom limb and accounts describing it date back to the 1800s. Similarly, many amputees are frequently aware of severe pain in the absent limb. Their pain is real and is often accompanied by other health problems, such as depression.

What causes this phenomenon? Scientists believe that following amputation, nerve cells "rewire" themselves and continue to receive messages, resulting in a remapping of the brain's circuitry. The brain's ability to restructure itself, to change and adapt following injury, is called plasticity (see section on Plasticity).

Our understanding of phantom pain has improved tremendously in recent years. Investigators previously believed that brain cells affected by amputation simply died off. They attributed sensations of pain at the site of the amputation to irritation of nerves located near the limb stump. Now, using imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI), scientists can actually visualize increased activity in the brain's cortex when an individual feels phantom pain. When study participants move the stump of an amputated limb, neurons in the brain remain dynamic and excitable. Surprisingly, the brain's cells can be stimulated by other body parts, often those located closest to the missing limb.

Treatments for phantom pain may include analgesics, anticonvulsants, and other types of drugs; nerve blocks; electrical stimulation; psychological counseling, biofeedback, hypnosis, and acupuncture; and, in rare instances, surgery.

Chili Peppers, Capsaicin, and Pain

The hot feeling, red face, and watery eyes you experience when you bite into a red chili pepper may make you reach for a cold drink, but that reaction has also given scientists important information about pain. The chemical found in chili peppers that causes those feelings is capsaicin (pronounced cap-SAY-sin), and it works its unique magic by grabbing onto receptors scattered along the surface of sensitive nerve cells in the mouth.

In 1997, scientists at the University of California at San Francisco discovered a gene for a capsaicin receptor, called the vanilloid receptor. Once in contact with capsaicin, vanilloid receptors open and pain signals are sent from the peripheral nociceptor and through central nervous system circuits to the brain. Investigators have also learned that this receptor plays a role in the burning type of pain commonly associated with heat, such as the kind you experience when you touch your finger to a hot stove. The vanilloid receptor functions as a sort of "ouch gateway," enabling us to detect burning hot pain, whether it originates from a 3-alarm habanera chili or from a stove burner.

Capsaicin is currently available as a prescription or over-the-counter cream for the treatment of a number of pain conditions, such as shingles. It works by reducing the amount of substance P found in nerve endings and interferes with the transmission of pain signals to the brain. Individuals can become desensitized to the compound, however, perhaps because of long-term damage to nerve tissue. Some individuals find the burning sensation they experience when using capsaicin cream to be intolerable, especially when they are already suffering from a painful condition, such as postherpetic neuralgia. Soon, however, better treatments that relieve pain by blocking vanilloid receptors may arrive in drugstores.

Marijuana

As a painkiller, marijuana or, by its Latin name, cannabis, continues to remain highly controversial. In the eyes of many individuals campaigning on its behalf, marijuana rightfully belongs with other pain remedies. In fact, for many years, it was sold under highly controlled conditions in cigarette form by the Federal government for just that purpose.

In 1997, the National Institutes of Health held a workshop to discuss research on the possible therapeutic uses for smoked marijuana. Panel members from a number of fields reviewed published research and heard presentations from pain experts. The panel members concluded that, because there are too few scientific studies to prove marijuana's therapeutic utility for certain conditions, additional research is needed. There is evidence, however, that receptors to which marijuana binds are found in many brain regions that process information that can produce pain.

Nerve Blocks

Nerve blocks may involve local anesthesia, regional anesthesia or analgesia, or surgery; dentists routinely use them for traditional dental procedures. Nerve blocks can also be used to prevent or even diagnose pain.

In the case of a local nerve block, any one of a number of local anesthetics may be used; the names of these compounds, such as lidocaine or novocaine, usually have an aine ending. Regional blocks affect a larger area of the body. Nerve blocks may also take the form of what is commonly called an epidural, in which a drug is administered into the space between the spine's protective covering (the dura) and the spinal column. This procedure is most well known for its use during childbirth. Morphine and methadone are opioid narcotics (such drugs end in ine or one) that are sometimes used for regional analgesia and are administered as an injection.

Neurolytic blocks employ injection of chemical agents such as alcohol, phenol, or glycerol to block pain messages and are most often used to treat cancer pain or to block pain in the cranial nerves (see The Nervous Systems). In some cases, a drug called guanethidine is administered intravenously in order to accomplish the block.

Surgical blocks are performed on cranial, peripheral, or sympathetic nerves. They are most often done to relieve the pain of cancer and extreme facial pain, such as that experienced with trigeminal neuralgia. There are several different types of surgical nerve blocks and they are not without problems and complications. Nerve blocks can cause muscle paralysis and, in many cases, result in at least partial numbness. For that reason, the procedure should be reserved for a select group of patients and should only be performed by skilled surgeons. Types of surgical nerve blocks include:

Neurectomy (including peripheral neurectomy) in which a damaged peripheral nerve is destroyed.
Spinal dorsal rhizotomy in which the surgeon cuts the root or rootlets of one or more of the nerves radiating from the spine. Other rhizotomy procedures include cranial rhizotomy and trigeminal rhizotomy, performed as a treatment for extreme facial pain or for the pain of cancer.
Sympathectomy, also called sympathetic blockade, in which a drug or an agent such as guanethidine is used to eliminate pain in a specific area (a limb, for example). The procedure is also done for cardiac pain, vascular disease pain, the pain of reflex sympathetic dystrophy syndrome, and other conditions. The term takes its name from the sympathetic nervous system (see The Nervous Systems) and may involve, for example, cutting a nerve that controls contraction of one or more arteries.

"Pain: Hope Through Research," NINDS. Publication date December 2001.

http://www.ninds.nih.gov/disorders/chronic_pain/detail_chronic_pain.htm

Wednesday, 22 February 2012

What Pain Is - PART 1

I very seldom recommend an article, or advise people strongly to read it. I generally let the reader make up his or her mind if the subject interests them or not. However, today's and tomorrow's two-part post from the National Institute of Neurological Disorders and Stroke (see link below) seems to me to be extremely useful for most people living with HIV and/or Neuropathy. It was written in 2001 but as you will see, very little has changed since then.
Sooner or later, it is possible that you will experience some HIV-related complaint which gives you pain. If it's not HIV-related then it's very helpful to be able to identify exactly what it is. HIV-patients are constantly excluding possiblities before getting to the source of their problem. That applies even more to people with neuropathy. It is so complex; with so many causes and forms, that getting to the root of your pain problem is liking walking through a minefield.
This article provides a sort of easily-understandable breakdown of the various forms of pain and how they're treated (including 'alternative' treatments). It's long (had to be split up over two days) but absolutely worth reading, even if you're not in pain yourself. It will help to calm the inbuilt hypochondria that people with HIV acquire through experience and enable them to rule out many of their worries. It may also give you a starting point for discussions with your doctor.


Pain: Hope Through Research
Prepared by:
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892


Introduction: The Universal Disorder

You know it at once. It may be the fiery sensation of a burn moments after your finger touches the stove. Or it's a dull ache above your brow after a day of stress and tension. Or you may recognize it as a sharp pierce in your back after you lift something heavy.

It is pain. In its most benign form, it warns us that something isn't quite right, that we should take medicine or see a doctor. At its worst, however, pain robs us of our productivity, our well-being, and, for many of us suffering from extended illness, our very lives. Pain is a complex perception that differs enormously among individual patients, even those who appear to have identical injuries or illnesses.

In 1931, the French medical missionary Dr. Albert Schweitzer wrote, "Pain is a more terrible lord of mankind than even death itself." Today, pain has become the universal disorder, a serious and costly public health issue, and a challenge for family, friends, and health care providers who must give support to the individual suffering from the physical as well as the emotional consequences of pain.

A Brief History of Pain

Ancient civilizations recorded on stone tablets accounts of pain and the treatments used: pressure, heat, water, and sun. Early humans related pain to evil, magic, and demons. Relief of pain was the responsibility of sorcerers, shamans, priests, and priestesses, who used herbs, rites, and ceremonies as their treatments.

The Greeks and Romans were the first to advance a theory of sensation, the idea that the brain and nervous system have a role in producing the perception of pain. But it was not until the Middle Ages and well into the Renaissance-the 1400s and 1500s-that evidence began to accumulate in support of these theories. Leonardo da Vinci and his contemporaries came to believe that the brain was the central organ responsible for sensation. Da Vinci also developed the idea that the spinal cord transmits sensations to the brain.

In the 17th and 18th centuries, the study of the body-and the senses-continued to be a source of wonder for the world's philosophers. In 1664, the French philosopher René Descartes described what to this day is still called a "pain pathway." Descartes illustrated how particles of fire, in contact with the foot, travel to the brain and he compared pain sensation to the ringing of a bell.

In the 19th century, pain came to dwell under a new domain-science-paving the way for advances in pain therapy. Physician-scientists discovered that opium, morphine, codeine, and cocaine could be used to treat pain. These drugs led to the development of aspirin, to this day the most commonly used pain reliever. Before long, anesthesia-both general and regional-was refined and applied during surgery.

"It has no future but itself," wrote the 19th century American poet Emily Dickinson, speaking about pain. As the 21st century unfolds, however, advances in pain research are creating a less grim future than that portrayed in Dickinson’s verse, a future that includes a better understanding of pain, along with greatly improved treatments to keep it in check.

The Two Faces of Pain: Acute and Chronic

What is pain? The International Association for the Study of Pain defines it as: An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.

It is useful to distinguish between two basic types of pain, acute and chronic, and they differ greatly.

Acute pain, for the most part, results from disease, inflammation, or injury to tissues. This type of pain generally comes on suddenly, for example, after trauma or surgery, and may be accompanied by anxiety or emotional distress. The cause of acute pain can usually be diagnosed and treated, and the pain is self-limiting, that is, it is confined to a given period of time and severity. In some rare instances, it can become chronic.
Chronic pain is widely believed to represent disease itself. It can be made much worse by environmental and psychological factors. Chronic pain persists over a longer period of time than acute pain and is resistant to most medical treatments. It can—and often does—cause severe problems for patients. A person may have two or more co-existing chronic pain conditions. Such conditions can include chronic fatigue syndrome, endometriosis, fibromyalgia, inflammatory bowel disease, interstitial cystitis, temporomandibular joint dysfunction, and vulvodynia. It is not known whether these disorders share a common cause.

The A to Z of Pain

Hundreds of pain syndromes or disorders make up the spectrum of pain. There are the most benign, fleeting sensations of pain, such as a pin prick. There is the pain of childbirth, the pain of a heart attack, and the pain that sometimes follows amputation of a limb. There is also pain accompanying cancer and the pain that follows severe trauma, such as that associated with head and spinal cord injuries. A sampling of common pain syndromes follows, listed alphabetically.

Arachnoiditis is a condition in which one of the three membranes covering the brain and spinal cord, called the arachnoid membrane, becomes inflamed. A number of causes, including infection or trauma, can result in inflammation of this membrane. Arachnoiditis can produce disabling, progressive, and even permanent pain.

Arthritis. Millions of Americans suffer from arthritic conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and gout. These disorders are characterized by joint pain in the extremities. Many other inflammatory diseases affect the body's soft tissues, including tendonitis and bursitis.

Back pain has become the high price paid by our modern lifestyle and is a startlingly common cause of disability for many Americans, including both active and inactive people. Back pain that spreads to the leg is called sciatica and is a very common condition (see below). Another common type of back pain is associated with the discs of the spine, the soft, spongy padding between the vertebrae (bones) that form the spine. Discs protect the spine by absorbing shock, but they tend to degenerate over time and may sometimes rupture. Spondylolisthesis is a back condition that occurs when one vertebra extends over another, causing pressure on nerves and therefore pain. Also, damage to nerve roots (see Spine Basics in the Appendix) is a serious condition, called radiculopathy, that can be extremely painful. Treatment for a damaged disc includes drugs such as painkillers, muscle relaxants, and steroids; exercise or rest, depending on the patient's condition; adequate support, such as a brace or better mattress and physical therapy. In some cases, surgery may be required to remove the damaged portion of the disc and return it to its previous condition, especially when it is pressing a nerve root. Surgical procedures include discectomy, laminectomy, or spinal fusion (see section on surgery in How is Pain Treated? for more information on these treatments).

Burn pain can be profound and poses an extreme challenge to the medical community. First-degree burns are the least severe; with third-degree burns, the skin is lost. Depending on the injury, pain accompanying burns can be excruciating, and even after the wound has healed patients may have chronic pain at the burn site.

Central pain syndrome-see "Trauma" below.

Cancer pain can accompany the growth of a tumor, the treatment of cancer, or chronic problems related to cancer's permanent effects on the body. Fortunately, most cancer pain can be treated to help minimize discomfort and stress to the patient.

Headaches affect millions of Americans. The three most common types of chronic headache are migraines, cluster headaches, and tension headaches. Each comes with its own telltale brand of pain.

Migraines are characterized by throbbing pain and sometimes by other symptoms, such as nausea and visual disturbances. Migraines are more frequent in women than men. Stress can trigger a migraine headache, and migraines can also put the sufferer at risk for stroke.
Cluster headaches are characterized by excruciating, piercing pain on one side of the head; they occur more frequently in men than women.
Tension headaches are often described as a tight band around the head.
Head and facial pain can be agonizing, whether it results from dental problems or from disorders such as cranial neuralgia, in which one of the nerves in the face, head, or neck is inflamed. Another condition, trigeminal neuralgia (also called tic douloureux), affects the largest of the cranial nerves (see The Nervous Systems in the Appendix) and is characterized by a stabbing, shooting pain.

Muscle pain can range from an aching muscle, spasm, or strain, to the severe spasticity that accompanies paralysis. Another disabling syndrome is fibromyalgia, a disorder characterized by fatigue, stiffness, joint tenderness, and widespread muscle pain. Polymyositis, dermatomyositis, and inclusion body myositis are painful disorders characterized by muscle inflammation. They may be caused by infection or autoimmune dysfunction and are sometimes associated with connective tissue disorders, such as lupus and rheumatoid arthritis.

Myofascial pain syndromes affect sensitive areas known as trigger points, located within the body's muscles. Myofascial pain syndromes are sometimes misdiagnosed and can be debilitating. Fibromyalgia is a type of myofascial pain syndrome.

Neuropathic pain is a type of pain that can result from injury to nerves, either in the peripheral or central nervous system (see The Nervous Systems in the Appendix). Neuropathic pain can occur in any part of the body and is frequently described as a hot, burning sensation, which can be devastating to the affected individual. It can result from diseases that affect nerves (such as diabetes) or from trauma, or, because chemotherapy drugs can affect nerves, it can be a consequence of cancer treatment. Among the many neuropathic pain conditions are diabetic neuropathy (which results from nerve damage secondary to vascular problems that occur with diabetes); reflex sympathetic dystrophy syndrome (see below), which can follow injury; phantom limb and post-amputation pain (see Phantom Pain in the Appendix), which can result from the surgical removal of a limb; postherpetic neuralgia, which can occur after an outbreak of shingles; and central pain syndrome, which can result from trauma to the brain or spinal cord.

Reflex sympathetic dystrophy syndrome, or RSDS, is accompanied by burning pain and hypersensitivity to temperature. Often triggered by trauma or nerve damage, RSDS causes the skin of the affected area to become characteristically shiny. In recent years, RSDS has come to be called complex regional pain syndrome (CRPS); in the past it was often called causalgia.

Repetitive stress injuries are muscular conditions that result from repeated motions performed in the course of normal work or other daily activities. They include:

Writer's cramp, which affects musicians and writers and others,
compression or entrapment neuropathies, including carpal tunnel syndrome, caused by chronic overextension of the wrist and
tendonitis or tenosynovitis, affecting one or more tendons.
Sciatica is a painful condition caused by pressure on the sciatic nerve, the main nerve that branches off the spinal cord and continues down into the thighs, legs, ankles, and feet. Sciatica is characterized by pain in the buttocks and can be caused by a number of factors. Exertion, obesity, and poor posture can all cause pressure on the sciatic nerve. One common cause of sciatica is a herniated disc (see Spine Basics in the Appendix).

Shingles and other painful disorders affect the skin. Pain is a common symptom of many skin disorders, even the most common rashes. One of the most vexing neurological disorders is shingles or herpes zoster, an infection that often causes agonizing pain resistant to treatment. Prompt treatment with antiviral agents is important to arrest the infection, which if prolonged can result in an associated condition known as postherpetic neuralgia. Other painful disorders affecting the skin include:

Vasculitis, or inflammation of blood vessels;
other infections, including herpes simplex;
skin tumors and cysts, and
tumors associated with neurofibromatosis, a neurogenetic disorder.

Sports injuries are common. Sprains, strains, bruises, dislocations, and fractures are all well-known words in the language of sports. Pain is another. In extreme cases, sports injuries can take the form of costly and painful spinal cord and head injuries, which cause severe suffering and disability.

Spinal stenosis refers to a narrowing of the canal surrounding the spinal cord. The condition occurs naturally with aging. Spinal stenosis causes weakness in the legs and leg pain usually felt while the person is standing up and often relieved by sitting down.

Surgical pain may require regional or general anesthesia during the procedure and medications to control discomfort following the operation. Control of pain associated with surgery includes presurgical preparation and careful monitoring of the patient during and after the procedure.

Temporomandibular disorders are conditions in which the temporomandibular joint (the jaw) is damaged and/or the muscles used for chewing and talking become stressed, causing pain. The condition may be the result of a number of factors, such as an injury to the jaw or joint misalignment, and may give rise to a variety of symptoms, most commonly pain in the jaw, face, and/or neck muscles. Physicians reach a diagnosis by listening to the patient's description of the symptoms and by performing a simple examination of the facial muscles and the temporomandibular joint.

Trauma can occur after injuries in the home, at the workplace, during sports activities, or on the road. Any of these injuries can result in severe disability and pain. Some patients who have had an injury to the spinal cord experience intense pain ranging from tingling to burning and, commonly, both. Such patients are sensitive to hot and cold temperatures and touch. For these individuals, a touch can be perceived as intense burning, indicating abnormal signals relayed to and from the brain. This condition is called central pain syndrome or, if the damage is in the thalamus (the brain's center for processing bodily sensations), thalamic pain syndrome. It affects as many as 100,000 Americans with multiple sclerosis, Parkinson's disease, amputated limbs, spinal cord injuries, and stroke. Their pain is severe and is extremely difficult to treat effectively. A variety of medications, including analgesics, antidepressants, anticonvulsants, and electrical stimulation, are options available to central pain patients.

Vascular disease or injury-such as vasculitis or inflammation of blood vessels, coronary artery disease, and circulatory problems-all have the potential to cause pain. Vascular pain affects millions of Americans and occurs when communication between blood vessels and nerves is interrupted. Ruptures, spasms, constriction, or obstruction of blood vessels, as well as a condition called ischemia in which blood supply to organs, tissues, or limbs is cut off, can also result in pain.

How is Pain Diagnosed?

There is no way to tell how much pain a person has. No test can measure the intensity of pain, no imaging device can show pain, and no instrument can locate pain precisely. Sometimes, as in the case of headaches, physicians find that the best aid to diagnosis is the patient's own description of the type, duration, and location of pain. Defining pain as sharp or dull, constant or intermittent, burning or aching may give the best clues to the cause of pain. These descriptions are part of what is called the pain history, taken by the physician during the preliminary examination of a patient with pain.

Physicians, however, do have a number of technologies they use to find the cause of pain. Primarily these include:

Electrodiagnostic procedures include electromyography (EMG), nerve conduction studies, and evoked potential (EP) studies. Information from EMG can help physicians tell precisely which muscles or nerves are affected by weakness or pain. Thin needles are inserted in muscles and a physician can see or listen to electrical signals displayed on an EMG machine. With nerve conduction studies the doctor uses two sets of electrodes (similar to those used during an electrocardiogram) that are placed on the skin over the muscles. The first set gives the patient a mild shock that stimulates the nerve that runs to that muscle. The second set of electrodes is used to make a recording of the nerve's electrical signals, and from this information the doctor can determine if there is nerve damage. EP tests also involve two sets of electrodes-one set for stimulating a nerve (these electrodes are attached to a limb) and another set on the scalp for recording the speed of nerve signal transmission to the brain.
Imaging, especially magnetic resonance imaging or MRI, provides physicians with pictures of the body's structures and tissues. MRI uses magnetic fields and radio waves to differentiate between healthy and diseased tissue.
A neurological examination in which the physician tests movement, reflexes, sensation, balance, and coordination.
X-rays produce pictures of the body's structures, such as bones and joints.

How is Pain Treated?

The goal of pain management is to improve function, enabling individuals to work, attend school, or participate in other day-to-day activities. Patients and their physicians have a number of options for the treatment of pain; some are more effective than others. Sometimes, relaxation and the use of imagery as a distraction provide relief. These methods can be powerful and effective, according to those who advocate their use. Whatever the treatment regime, it is important to remember that pain is treatable. The following treatments are among the most common.

Acetaminophen is the basic ingredient found in Tylenol® and its many generic equivalents. It is sold over the counter, in a prescription-strength preparation, and in combination with codeine (also by prescription).

Acupuncture dates back 2,500 years and involves the application of needles to precise points on the body. It is part of a general category of healing called traditional Chinese or Oriental medicine. Acupuncture remains controversial but is quite popular and may one day prove to be useful for a variety of conditions as it continues to be explored by practitioners, patients, and investigators.

Analgesic refers to the class of drugs that includes most painkillers, such as aspirin, acetaminophen, and ibuprofen. The word analgesic is derived from ancient Greek and means to reduce or stop pain. Nonprescription or over-the-counter pain relievers are generally used for mild to moderate pain. Prescription pain relievers, sold through a pharmacy under the direction of a physician, are used for more moderate to severe pain.

Anticonvulsants are used for the treatment of seizure disorders but are also sometimes prescribed for the treatment of pain. Carbamazepine in particular is used to treat a number of painful conditions, including trigeminal neuralgia. Another antiepileptic drug, gabapentin, is being studied for its pain-relieving properties, especially as a treatment for neuropathic pain.

Antidepressants are sometimes used for the treatment of pain and, along with neuroleptics and lithium, belong to a category of drugs called psychotropic drugs. In addition, anti-anxiety drugs called benzodiazepines also act as muscle relaxants and are sometimes used as pain relievers. Physicians usually try to treat the condition with analgesics before prescribing these drugs.

Antimigraine drugs include the triptans- sumatriptan (Imitrex®), naratriptan (Amerge®), and zolmitriptan (Zomig®)-and are used specifically for migraine headaches. They can have serious side effects in some people and therefore, as with all prescription medicines, should be used only under a doctor's care.

Aspirin may be the most widely used pain-relief agent and has been sold over the counter since 1905 as a treatment for fever, headache, and muscle soreness.

Biofeedback is used for the treatment of many common pain problems, most notably headache and back pain. Using a special electronic machine, the patient is trained to become aware of, to follow, and to gain control over certain bodily functions, including muscle tension, heart rate, and skin temperature. The individual can then learn to effect a change in his or her responses to pain, for example, by using relaxation techniques. Biofeedback is often used in combination with other treatment methods, generally without side effects. Similarly, the use of relaxation techniques in the treatment of pain can increase the patient's feeling of well-being.

Capsaicin is a chemical found in chili peppers that is also a primary ingredient in pain-relieving creams (see Chili Peppers, Capsaicin, and Pain in the Appendix).

Chemonucleolysis is a treatment in which an enzyme, chymopapain, is injected directly into a herniated lumbar disc (see Spine Basics in the Appendix) in an effort to dissolve material around the disc, thus reducing pressure and pain. The procedure's use is extremely limited, in part because some patients may have a life-threatening allergic reaction to chymopapain.

Chiropractic
care may ease back pain, neck pain, headaches, and musculoskeletal conditions. It involves "hands-on" therapy designed to adjust the relationship between the body's structure (mainly the spine) and its functioning. Chiropractic spinal manipulation includes the adjustment and manipulation of the joints and adjacent tissues. Such care may also involve therapeutic and rehabilitative exercises.

Cognitive-behavioral therapy involves a wide variety of coping skills and relaxation methods to help prepare for and cope with pain. It is used for postoperative pain, cancer pain, and the pain of childbirth.

Counseling can give a patient suffering from pain much needed support, whether it is derived from family, group, or individual counseling. Support groups can provide an important adjunct to drug or surgical treatment. Psychological treatment can also help patients learn about the physiological changes produced by pain.

COX-2 inhibitors may be effective for individuals with arthritis. For many years scientists have wanted to develop a drug that works as well as morphine but without its negative side effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) work by blocking two enzymes, cyclooxygenase-1 and cyclooxygenase-2, both of which promote production of hormones called prostaglandins, which in turn cause inflammation, fever, and pain. The newer COX-2 inhibitors primarily block cyclooxygenase-2 and are less likely to have the gastrointestinal side effects sometimes produced by NSAIDs.

In 1999, the Food and Drug Administration approved a COX-2 inhibitor-celecoxib-for use in cases of chronic pain. The long-term effects of all COX-2 inhibitors are still being evaluated, especially in light of new information suggesting that these drugs may increase the risk of heart attack and stroke. Patients taking any of the COX-2 inhibitors should review their drug treatment with their doctors.

Electrical stimulation, including transcutaneous electrical stimulation (TENS), implanted electric nerve stimulation, and deep brain or spinal cord stimulation, is the modern-day extension of age-old practices in which the nerves of muscles are subjected to a variety of stimuli, including heat or massage. Electrical stimulation, no matter what form, involves a major surgical procedure and is not for everyone, nor is it 100 percent effective. The following techniques each require specialized equipment and personnel trained in the specific procedure being used:

TENS
uses tiny electrical pulses, delivered through the skin to nerve fibers, to cause changes in muscles, such as numbness or contractions. This in turn produces temporary pain relief. There is also evidence that TENS can activate subsets of peripheral nerve fibers that can block pain transmission at the spinal cord level, in much the same way that shaking your hand can reduce pain.
Peripheral nerve stimulation uses electrodes placed surgically on a carefully selected area of the body. The patient is then able to deliver an electrical current as needed to the affected area, using an antenna and transmitter.
Spinal cord stimulation uses electrodes surgically inserted within the epidural space of the spinal cord. The patient is able to deliver a pulse of electricity to the spinal cord using a small box-like receiver and an antenna taped to the skin.
Deep brain or intracerebral stimulation is considered an extreme treatment and involves surgical stimulation of the brain, usually the thalamus. It is used for a limited number of conditions, including severe pain, central pain syndrome, cancer pain, phantom limb pain, and other neuropathic pains.

Exercise has come to be a prescribed part of some doctors' treatment regimes for patients with pain. Because there is a known link between many types of chronic pain and tense, weak muscles, exercise-even light to moderate exercise such as walking or swimming-can contribute to an overall sense of well-being by improving blood and oxygen flow to muscles. Just as we know that stress contributes to pain, we also know that exercise, sleep, and relaxation can all help reduce stress, thereby helping to alleviate pain. Exercise has been proven to help many people with low back pain. It is important, however, that patients carefully follow the routine laid out by their physicians.

Hypnosis, first approved for medical use by the American Medical Association in 1958, continues to grow in popularity, especially as an adjunct to pain medication. In general, hypnosis is used to control physical function or response, that is, the amount of pain an individual can withstand. How hypnosis works is not fully understood. Some believe that hypnosis delivers the patient into a trance-like state, while others feel that the individual is simply better able to concentrate and relax or is more responsive to suggestion. Hypnosis may result in relief of pain by acting on chemicals in the nervous system, slowing impulses. Whether and how hypnosis works involves greater insight-and research-into the mechanisms underlying human consciousness.

Ibuprofen is a member of the aspirin family of analgesics, the so-called nonsteroidal anti-inflammatory drugs (see below). It is sold over the counter and also comes in prescription-strength preparations.

Low-power lasers have been used occasionally by some physical therapists as a treatment for pain, but like many other treatments, this method is not without controversy.

Magnets are increasingly popular with athletes who swear by their effectiveness for the control of sports-related pain and other painful conditions. Usually worn as a collar or wristwatch, the use of magnets as a treatment dates back to the ancient Egyptians and Greeks. While it is often dismissed as quackery and pseudoscience by skeptics, proponents offer the theory that magnets may effect changes in cells or body chemistry, thus producing pain relief.

Narcotics (see Opioids, below).

Nerve blocks employ the use of drugs, chemical agents, or surgical techniques to interrupt the relay of pain messages between specific areas of the body and the brain. There are many different names for the procedure, depending on the technique or agent used. Types of surgical nerve blocks include neurectomy; spinal dorsal, cranial, and trigeminal rhizotomy; and sympathectomy, also called sympathetic blockade (see Nerve Blocks in the Appendix).

Nonsteroidal anti-inflammatory drugs (NSAIDs) (including aspirin and ibuprofen) are widely prescribed and sometimes called non-narcotic or non-opioid analgesics. They work by reducing inflammatory responses in tissues. Many of these drugs irritate the stomach and for that reason are usually taken with food. Although acetaminophen may have some anti-inflammatory effects, it is generally distinguished from the traditional NSAIDs.

Opioids are derived from the poppy plant and are among the oldest drugs known to humankind. They include codeine and perhaps the most well-known narcotic of all, morphine. Morphine can be administered in a variety of forms, including a pump for patient self-administration. Opioids have a narcotic effect, that is, they induce sedation as well as pain relief, and some patients may become physically dependent upon them. For these reasons, patients given opioids should be monitored carefully; in some cases stimulants may be prescribed to counteract the sedative side effects. In addition to drowsiness, other common side effects include constipation, nausea, and vomiting.

Physical therapy and rehabilitation date back to the ancient practice of using physical techniques and methods, such as heat, cold, exercise, massage, and manipulation, in the treatment of certain conditions. These may be applied to increase function, control pain, and speed the patient toward full recovery.

Placebos offer some individuals pain relief although whether and how they have an effect is mysterious and somewhat controversial. Placebos are inactive substances, such as sugar pills, or harmless procedures, such as saline injections or sham surgeries, generally used in clinical studies as control factors to help determine the efficacy of active treatments. Although placebos have no direct effect on the underlying causes of pain, evidence from clinical studies suggests that many pain conditions such as migraine headache, back pain, post-surgical pain, rheumatoid arthritis, angina, and depression sometimes respond well to them. This positive response is known as the placebo effect, which is defined as the observable or measurable change that can occur in patients after administration of a placebo. Some experts believe the effect is psychological and that placebos work because the patients believe or expect them to work. Others say placebos relieve pain by stimulating the brain's own analgesics and setting the body's self-healing forces in motion. A third theory suggests that the act of taking placebos relieves stress and anxiety-which are known to aggravate some painful conditions-and, thus, cause the patients to feel better. Still, placebos are considered controversial because by definition they are inactive and have no actual curative value.

R.I.C.E.-Rest, Ice, Compression, and Elevation-are four components prescribed by many orthopedists, coaches, trainers, nurses, and other professionals for temporary muscle or joint conditions, such as sprains or strains. While many common orthopedic problems can be controlled with these four simple steps, especially when combined with over-the-counter pain relievers, more serious conditions may require surgery or physical therapy, including exercise, joint movement or manipulation, and stimulation of muscles.

Surgery, although not always an option, may be required to relieve pain, especially pain caused by back problems or serious musculoskeletal injuries. Surgery may take the form of a nerve block (see Nerve Blocks in the Appendix) or it may involve an operation to relieve pain from a ruptured disc. Surgical procedures for back problems include discectomy or, when microsurgical techniques are used, microdiscectomy, in which the entire disc is removed; laminectomy, a procedure in which a surgeon removes only a disc fragment, gaining access by entering through the arched portion of a vertebra; and spinal fusion, a procedure where the entire disc is removed and replaced with a bone graft. In a spinal fusion, the two vertebrae are then fused together. Although the operation can cause the spine to stiffen, resulting in lost flexibility, the procedure serves one critical purpose: protection of the spinal cord. Other operations for pain include rhizotomy, in which a nerve close to the spinal cord is cut, and cordotomy, where bundles of nerves within the spinal cord are severed. Cordotomy is generally used only for the pain of terminal cancer that does not respond to other therapies. Another operation for pain is the dorsal root entry zone operation, or DREZ, in which spinal neurons corresponding to the patient's pain are destroyed surgically. Because surgery can result in scar tissue formation that may cause additional problems, patients are well advised to seek a second opinion before proceeding. Occasionally, surgery is carried out with electrodes that selectively damage neurons in a targeted area of the brain. These procedures rarely result in long-term pain relief, but both physician and patient may decide that the surgical procedure will be effective enough that it justifies the expense and risk. In some cases, the results of an operation are remarkable. For example, many individuals suffering from trigeminal neuralgia who are not responsive to drug treatment have had great success with a procedure called microvascular decompression, in which tiny blood vessels are surgically separated from surrounding nerves.
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See Part 2 tomorrow

http://www.ninds.nih.gov/disorders/chronic_pain/detail_chronic_pain.htm