Wednesday, 30 November 2011

How Professionals Look at Neuropathic Pain - PART ONE

Whether you are going to your first appointment with a doctor, or are an experienced neuropathy patient, I cannot stress enough how useful the two posts from (see link below) of today and tomorrow may be to you.
They provide both an insight and an overview into best practice concerning neuropathic pain, both its cause and its treatment. As a neuropathy patient, you should be entitled to the sensible and sympathetic approach that is advised here. It's refreshing to see that its starting premise is that your pain must be taken seriously!
The fact that the information both today and tomorrow is meant for other professionals and medical students does not mean that you're not entitled to read it. Not all of it will apply to your particular case but at least you will have an excellent source of information and alternatives, from which your treatment should emerge.

Treating Neuropathic Pain And The Neuropathic Pain Patient - PART ONE
John T. Farrar, MD, MSCE - Last Modified: Monday, 16-May-2011
Departments of Anesthesiology, Neurology, and Epidemiology, the Center for Clinical Epidemiology and Biostatistics, the University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania.


Neurologists have the option of choosing from among numerous drugs and drug classes when treating neuropathic pain. The challenge, therefore, lies not in having limited options for treatment, but in the art of practicing medicine, i.e., of identifying neuropathic pain and empathizing with the patient without the benefit of either an objective test or a complete understanding of pain pathophysiology, and providing the best evidence-based options for therapy. The International Association for the Study of Pain definition of pain - a sensory and emotional experience, signaling actual or potential tissue damage - illustrates the dual nature, both objective and subjective, of this condition. The neurologist's unique understanding of the complex interactions that occur in the nervous system can provide a significant contribution to the care of patients with pain.

Additionally, we must remember that many patients, unable to quantitatively describe their pain and witnessing the medical community's lack of codified remedies, leave the physician's office thinking that the practitioner views their pain, even when incapacitating, as psychosomatic. An equally important role of the practicing neurologist, therefore, is to acknowledge the patient's experience of pain without attempting to validate its source. This article includes strategies for approaching a neuropathic pain patient, useful methods to treat the whole patient, and a discussion of why a holistic approach is important. An overview of the pharmacotherapies available for the treatment of neuropathic pain and their role in treating the whole patient is also provided.

Copyright 2001 Galen Publishing, LLC. First published in the September 2001 issue of Advanced Studies in Medicine, New Developments in the Management of Migraine and Neuropathic Pain (Volume 1, Number 6: 241-247),

Treating neuropathic pain means treating the neuropathic pain patient by first understanding what the patient is experiencing. This can be difficult, as there are no empirical tests for pain. Yet, the pain is completely real to the patient, and may even be incapacitating. The primary role of the physician is to make the appropriate diagnosis and focus treatment on the most important features of the patient's pain as reported by the patient. This should always include the presumed underlying pathophysiologic mechanism but must also focus on other contributing factors, some of which may be more amenable to treatment than the primary process.

What Is Pain?

The International Association for the Study of Pain (IASP) defines pain as: "The unpleasant sensory and emotional experience of actual or potential tissue damage or an experience expressed in such terms."1 Since pain is both a sensory and an emotional experience (i.e., it affects the whole person), the whole person must be treated. The degree of pain intensity can be affected by the patient's attitude and perceptions of his surroundings. A broken toe will seem less painful if injured on the way to the airport to start one's vacation than if this takes place on the way to an Internal Revenue Service audit. Similarly, a cancer patient with back pain will experience a lessening of pain when assured by the physician that the pain is not indicative of metastasis or recurrence of the cancer. In fact, the use of environmental factors for managing pain intensity, known as distraction therapy, is widely used by practitioners and patients to help patients perform daily activities in spite of pain and other discomforts. The popularity of distraction therapies is the result of its demonstrated effectiveness in both the laboratory and the clinical setting.2

Despite the exponential growth of our knowledge about the brain in recent years, we do not yet understand the intricate pathophysiological mechanisms of neuropathic pain. We do, however, know that the brain, through the production of hormones and direct nerve connections from the brain to the pain fibers, is capable of far more control over the pain system than was previously thought. Yet since we have not identified a means to specifically harness this descending control system, a physician's best hope for providing effective treatment is to present patients with the various pain-management strategies and to support them in their search for the one or ones that work, remembering that efficacy is subjective and patient specific, much like in the treatment of psychiatric illness. Similarly, the success of treatment can be assessed only by individual patients reporting on changes in their symptoms.

The IASP definition of pain also includes the phrase "actual or potential tissue damage or an experience expressed in such terms." Acute pain is experienced immediately upon injury and notifies the individual of tissue damage. Neuropathic pain is caused by nerve damage proximal to the sensory nerve endings in the skin. Neuropathic pain has no protective or predictive value, because it persists long after tissue (i.e., nerve) damage has occurred. In essence, the lack of a specific measure of tissue damage does not preclude the sensation of pain.

Patients with neuropathic pain may also report fatigue, difficulty in concentrating, depression, and insomnia, and the severity of these symptoms may seem disproportionately high relative to the initial injury. Again, the most effective approach is to acknowledge the patient's discomfort and make a commitment to treat the pain. The hope gained from knowing that the physician will attempt to treat one's pain provides an effective distraction.

Types of Pain

The 3 types of pain (somatic, neuropathic, and visceral) are often co-occurring or comorbid as a mixed syndrome, so treating the neuropathic component may only treat part of the patient's symptoms. Most pain patients, especially those with chronic pain, have a mixed syndrome (neuropathic and somatic pain). Unlike somatic pain, which comes from specialized nerve endings and warns of tissue damage, neuropathic pain comes directly from nerve dysfunction and does not imply ongoing damage. It is important for physicians to explain this distinction to patients, who will be reassured when they learn that their pain does not signal continuous damage and may not be the harbinger of a more serious illness.

A common example of this mixed somatic/neuropathic syndrome is compression of a small nerve in the spine (neuropathic), which leads to muscle spasm (somatic). The body responds to the pain of compression by protecting the area through spasms, which create muscle pain in the area as well as other inflammatory responses. While the patient feels the muscle pain, the underlying pathology can be neuropathic. In treatment, therefore, residual pain after treating somatic pain should be considered an indication of possible neuropathic pain, even if the symptomatic features of the neuropathic pain are not predominant.

There are several neuropathic pain syndromes, outlined in Table 1, that are the result of ectopic generators, nerve trunk pain, microenvironmental changes, central alterations, and changes in the balance of nociceptor and nonnociceptor fibers. At this time, it is not yet possible to determine which of these factors specifically cause an individual's neuropathic pain. However, all of these factors can result in sensory loss, paresthesias (positive numbness or tingling), dysesthesias (painful or unpleasant burning, tingling or electric shock phenomenon), hyperesthesia (increased perception of mildly painful stimuli), hyperpathia (subthreshold stimuli producing pain), or allodynia (nonpainful stimuli producing pain).

Table 1. Common Types of Neuropathic Pain*

Examples of peripheral neuropathic pain
•Carpal tunnel syndrome
•Complex regional pain syndrome
•Human immunodeficiency virus (HIV) sensory neuropathy
•Meralgia paresthetica
•Painful diabetic neuropathy
•Phantom limb pain
•Postherpetic neuralgia
•Postthoracotomy pain
•Trigeminal neuralgia
Examples of central neuropathic pain •Central poststroke pain
•HIV myelopathy
•Multiple sclerosis pain
•Parkinson's disease pain
•Spinal cord injury pain
Examples of cancer-associated neuropathic pain •Chemotherapy-induced polyneuropathy
•Neuropathy secondary to tumor infiltration or nerve compression
•Phantom breast pain
•Postmastectomy pain
•Postradiation plexopathy and myelopathy
*Reprinted with permission from A Clinical Guide to Neuropathic Pain. Galer BS, Dworkin RH, eds. Minneapolis, MN: McGraw-Hill Healthcare Information; 2000.
PART TWO tomorrow (How neuropathy is treated)

Tuesday, 29 November 2011

Does Avandia (rosiglitazone) Signify a Neuropathy Breakthrough?

Thanks to studies and research from the University of Tokio, the diabetes drug, Avandia (rosiglitazone) is being hailed as a possible new drug for the treatment of neuropathy but like so many other drugs, it's not without its side effects and possible dangers. This scientific article from (see link below) discusses how it works and why it's being promoted as a possible breakthrough.
Unfortunately, from studies of diabetics, it has been found that Avandia can trigger fluid retention and congestive heart failure in certain patients, due to an unwanted effects on kidney function.
Avandia has been particularly controversial since 2007. A growing body of evidence suggests Avandia may increase the risk of heart disease and death, compared to other types of diabetes medications. The studies are not definitive, but given the lack of any significant advantage of Avandia over alternatives, few doctors see any reason to prescribe Avandia any more.
So where does that leave us? Are long-suffering HIV-patients going to be guinea pigs again and be exposed to unnecessary risks? One would assume that all necessary trials and tests will be carried out but it's always worth knowing the facts behind a drug before using it. It seems wise in this case to keep an eye out for any further news about Avandia.

Diabetes drug may help prevent neuropathic pain
July 26, 2011

The diabetes drug rosiglitazone (Avandia) can control inflammation leading to nerve damage and abnormal pain responses, suggests a paper in the August issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

Rosiglitazone works by blocking a specific pathway—PPAR-gamma—which appears to play a critical role in the development of disabling neuropathic pain. "We therefore propose PPAR-gamma regulation of the macrophage-mediated inflammatory response as a novel therapeutic target for treating neuropathic pain development," concludes the study by Dr Yoshika Takahashi and colleagues of Juntendo University School of Medicine, Tokyo.

The researchers performed a series of experiments to evaluate rosiglitazone's effects on the development of abnormal pain responses and neuropathic pain. Neuropathic pain is a common and difficult-to-treat type of pain caused by nerve damage, seen in patients with trauma, diabetes, and other conditions. Phantom limb pain after amputation is an example of neuropathic pain.

The experiments used a standard technique to induce nerve injury in the hind leg of mice. They then evaluated the effects of rosiglitazone, administered in different ways, on the development of abnormal pain responses and neuropathic pain.

Treatment with rosiglitazone after nerve injury reduced the development of "tactile allodynia"—painful responses to stimuli (such as light touching) that are not normally painful. Rosiglitazone also led to decreased inflammation in the area of nerve injury, as shown by reduced levels of various inflammatory markers. The reduction in inflammation was associated with decreased responses by macrophages—immune cells that play a key role in the inflammatory response to injury.

The reductions in abnormal pain responses were seen with different forms of rosiglitazone administration—not only systemic injection, but also local injection directly into the site of nerve injury. Animals injected with rosiglitazone-treated macrophages also had reduced inflammation and pain responses.

Rosiglitazone was developed as an insulin-sensitizer for the treatment of diabetes. However, use of this medication has been restricted since it was linked to an increased risk of heart attack and other safety problems.

Since rosiglitazone blocks PPAR-gamma, the results strongly suggest that the PPAR-gamma pathway plays a critical role in the development of nerve inflammation and abnormal pain responses—and thus in the development of neuropathic pain. "Our results indicate that the activation of PPAR-gamma signaling in macrophages during the early phase may suppress neuropathic pain development," Dr Takahashi and co-authors write.

The study provides important new clues about the early stages of the "neuroinflammatory" response to nerve injury, leading to the development of allodynia and neuropathic pain. With further research, rosiglitazone or other drugs affecting PPAR-gamma and the macrophage-mediated pain response could provide a valuable new approach for prevention or treatment of neuropathic pain.

Source: News Release
International Anesthesia Research Society (IARS)
July 25, 2011

Monday, 28 November 2011

Should Pain Still be Tolerated?

Today's post is another short article from The Pain Web (see link below)by Dr.J.C.D. Wells. He talks about how pain has been managed in the past and how its control is still a matter of debate amongst doctors. The question posed is, whether it is ethical in the modern age to allow a patient to live with extreme pain. Is there ever any justification for ignoring the impairment of a patient's life due to pain? You may think it is a no-brainer but many health professionals are extremely reluctant to use the strongest pain suppressants.

There's No Excuse for Pain
Dr J C D Wells Liverpool, UK

Pain has been underestimated and under-treated for hundreds of years. Interestingly, this was not always the case - the physicians of Greece and Rome took pain seriously and used the same medications that we use today. However, in the 18th century we can see the prevailing attitude in Britain and Ireland was to ignore pain, with soldiers and sailors having a leg amputated with nothing more than a draught of alcohol and women being expected to suffer labour uncomplainingly. It was only when Queen Victoria requested anaesthesia for the birth of her child that obstetric analgesia became acceptable. Also, the anaesthetic movement came in then to protect patients from the negative effects of pain during surgery.

Little else happened for the next hundred years in the management of acute, chronic or cancer pain. Then the hospice movement in Britain started to progress ideas about managing cancer pain, and you have already heard how things have developed, and the situation today. Chronic pain started to be taken seriously at the same time and was managed by pioneers such as John Bonica in the USA and Sam Lipton in the UK. However, facilities were poor and the service was always under-funded.

In the '90s, Anaesthetists really began to take a strong interest in the management of acute pain. Acute pain teams have been set up all over the Western world. Management of post-operative pain is still patchy, but certainly better than it was. But what about the management of chronic pain?

There certainly seems no argument that pain has a negative physical and mental effect upon the sufferer. There are also social and behavioural changes which occur and which can lead to chronicity. How sad then that in everyday practice we see doctors and paramedical staff ignoring or belittling a patient's complaints of pain. For instance, every week I get a letter from a doctor who tells me that an elderly patient cannot have medication for his pain because it will "interfere" with the essential drugs that he is having to produce diuresis, lower his blood pressure, stabilise his heart and expand his lungs. What is the point of prolonging life if the patient is in constant pain? Is it ethical to prolong a painful life? It is certainly unethical in my opinion to under-treat people with chronic pain.

A wide variety of treatments are recommended for pain, and perhaps some of the reluctance to treat stems from a lack of clinical evidence. This can be hard to obtain. I would fully concur that it should be obtained but, in the meantime whilst it is being sought, I would decry the nihilistic attitude of those who state that we should do nothing.

The treatments being used need to be constantly appraised, modified and updated. Assessment of the patient, their underlying pathology and their complaint of pain is paramount. When this assessment has been made, treatments can be tailored to the patient's need.

There are many ethical problems in the management of pain. These include the decision to treat, the decision not to treat, the use of treatments which haven't as yet been proven to be effective and the use of drugs, such as epidural steroids and anticonvulsants, for unlicenced indications. However, if modern techniques are assessed as accurately as the Greek and Roman physicians evaluated poppy juice and willow bark 2000 years ago, the lot of the average pain sufferer can be greatly improved.

Sunday, 27 November 2011

Is Meditation a Real Option for Neuropathy?

Today's post comes via - an HIV site that looks very carefully at what many call, 'alternative' methods of coping with the disease (see link below). This excellent personal account from Gordon Waselnuk, tells of his search for pain relief, both physical and psychological, via eastern meditation techniques. To my mind, you need to be openminded as to what has worked for other people and that can be very difficult when you're in pain and dependant on chemical pain relievers. However, Gordon's story shows how he broke through the negativity barrier to achieve something meaningful for himself. Cynics may put a negative slant on the word 'alternative' but if it's going to help you, it would be unwise to dismiss it out of hand. It's one of those subjects that you either embrace or not but reading this rather long post may change your mind, or reinforce what you already believe.

Breathing Lessons

Pain can be a great motivator.

It’s what drove me several months after the death of my lover 10 years ago to pack my bags and head off to Asia for respite. In Yanghshou, China, a small poster caught my eye. It offered a 10-day silent Vipassana retreat at a Buddhist monastery on a beautiful island in Thailand. Though I knew nothing about meditation or Buddhism, something inside said “go.”

Two weeks later I was climbing a hill on Kho Phangnan to the monastery Wat Kow Tham. The monks and nuns looked beautiful in their saffron and white robes. The golden images of the Buddha glistened in the tropical sunlight. Magical! If they only knew how screwed up I felt inside. I didn’t always feel that way. Many years ago I was a “successful” gay man with a great job, cool apartment, firm body and cute longtime lover, Richard. Life was fabulous! But in November 1989, Richard told me he was having stomach pain. Two months later, after numerous tests, we were hit over the head with a sledgehammer. Diagnosis: AIDS. My life fell apart. The next six months were a blur of hospitals, invasive therapies, anger, denial, bargaining and, finally, Richard withering away and dying. How could this happen to us? Intense anger, fear, anxiety, loneliness and an HIV diagnosis of my own followed. I felt lost in the dark, trapped in an unending storm. I needed a refuge.

This pain was what I carried with me—and maybe what carried me— up that hill to the monastery. At the introductory talk I sat at the back of the hall, ready to make a quick exit if the teachers started to sound like the Manson family. They explained the basics: Vipassana (insight, mindfulness) meditation is not a religion but rather a philosophy of living based on Buddhist teachings that is open to everyone — yes, it’s queer friendly. There is no guru or higher being to worship and you can incorporate it with other beliefs. The goal is to lessen your suffering and ignorance and live for higher values such as compassion, understanding and loving-kindness for yourself and others.

I moved a bit closer as the teachers continued: Through a daily meditation practice, including reflection, our awareness is able to slowly expand. We become mindful of our thoughts, feelings, actions and reactions. As we become more aware, we’ll be in a better position to understand the cause and effect of our actions. We need to practice on a regular basis to experience and understand these benefits.

I was sold.

Learning to surrender

My 10 days at the monastery involved daily lectures and meditation. The teachers’ wish was for us to incorporate mindfulness and this philosophy of living into our everyday lives. As the days passed, I sensed deeply, experientially, that I’d found something very valuable. I learned to “be” with whatever was happening with acceptance, noticing the impermanent nature of everything.

Sometimes grief would wash over me like a strong wave and tears would stream down my face. With the tools meditation was giving me, I could let myself experience this emotion fully but not attach any mental story to it. I kept coming back into my body to notice how this feeling manifested itself —my heart was beating faster, I felt a tightness in my stomach. Basically, I was experiencing grief but not fuelling or resisting it with thoughts of fear, anger or doubt. My breath became more rhythmic, less shallow or heavy. The moment felt safer and saner.

This technique has become beneficial to me as someone living with HIV, at times, for instance, when I feel physical pain or side effects from drugs, and it works synergistically with pain medication. Sometimes we just don’t feel well. If we can change that, great — if not, then we may as well accept it. It is in the acceptance that we eventually transcend it. We may not always have control over our health and environment, but we do have a say in how we react to it. This is a very powerful insight.

A decade has passed since that first retreat. The first year was a challenge but I persevered and kept practicing, going on five more retreats. Now I meditate every day. It has benefitted me emotionally, physically and spiritually in a huge way. By spending quiet time alone each day, I’ve been able to slowly develop a more intimate personal relationship with myself. Though friends, family and caregivers can offer us support, we can’t depend on them to always be there for us. With meditation, I’ve found a refuge where I can nurture, comfort and support myself. That refuge is me.

Listen to your body

In the daily silence of my meditation practice, I am much more aware of subtle changes in my body. By paying attention, we can slowly develop our intuitive nature. Are you listening to what your body is telling you? Immune dysfunction sometimes creeps up on us — a slight slide in energy, weight, muscle mass, libido, mild depression. Often we ignore it or are uncertain until it becomes a more serious problem. By noticing problems early on and being able to act, we are in a much better position to slow down or reverse symptoms. We’re also able to clearly describe the symptoms to our caregivers: how it manifests, what it feels like. Pieces of a puzzle. On the flip side, we can also recognize subtle benefits of therapy, such as surges in energy or a feeling of vitality. Noticing improvements can do wonders for the spirit and may help you maintain your adherence to whatever therapy you use. You’ll also have more energy, slow down the aging process and look prettier. I may not need to say more after that bombshell, but the truth is that meditation will beautify your soul and help remove some of the internal barriers we sometimes have.

Accentuate the positive

In the silence of meditation, we also begin to notice negative patterns, such as self-defeating behaviour and conditioning. Compassion, understanding, forgiveness, self-nurturing and loving-kindness are reflections and affirmations we voice and visualize after meditating. This is a powerful tool for breaking through those internal walls. You can create your own reflections and affirmations.

I reflect on how fortunate I am to be growing. I ask to be grateful for simple things, which helps to alleviate any “poor me” feelings I may have from time to time. I ask to have more compassion and love for myself and others. How we view ourselves and the world determines our capacity for joy and peace of mind. Meditation is also the best tool I’ve found for stress reduction. When I feel fear, doubt or worry, I simply note it and then focus on my breathing without reacting in my usual manner. By observing our thoughts and feelings — noting them but not being consumed by them — they eventually have less control over us, and we’re able to calm down and be more objective. Research backs up what I’ve experienced. A University of Miami study of 450 HIV positive women found that those women who used meditation and group therapy were significantly less depressed than those who didn’t; plus, they had better adherence to their medication. Another study, of 21 HIV positive gay men using meditation, moderate exercise and positive affirmations, found that those who kept up these practices after two years were less likely to be in denial about their diagnosis and had lower rates of progression to disease.

I encourage you to find a daily practice. It could be like mine — 20 minutes of sitting meditation plus reflection in the morning — or something that involves movement, such as yoga, tai chi or chi gong. Whatever does it for you. The key is to make a daily effort to live life more mindfully and lovingly. A skilled teacher and group setting are ideal for beginners. (Be aware that people with mood disorders, schizophrenia or serious depression are not advised to practice.) Some retreats are by donation. Look for announcements in local health journals or new-age magazines or contact a local meditation group or AIDS service organization. I wish you a wonderful journey of discovery as you climb your own hill.


1) Find a quiet space. Unplug the phone, put out the cat.

2) Sit comfortably in a chair or on a cushion with your eyes gently closed.

3) Stay present. Let go of any thoughts.

4) Slowly become aware of your breathing.

5) Notice the air coming in and out of your nostrils or the rising and
falling of your belly.

6) Follow the rhythm of your breath.

7) Don't try to control your breathing. Let it flow naturally. Some
breaths will be longer, some shorter.

8) To remain focused on the breath, simply note 'in' as you inhale and
'out' as you exhale.

9) When your mind wanders, simply make a mental note of observance
('my mind is wandering' or 'the cat is scratching at the door'). Then
come back to noticing your breath without getting angry or frustrated.

I never said meditation doesn't take effort! Eventually it will become
easier and habit-forming. Doing this practice twice a day for 20 minutes
is ideal, but even five minutes can be beneficial. If you miss a few days,
forgive yourself and begin again. It's in the trying where we grow.[p12_13].pdf

Saturday, 26 November 2011

Unhealthy Behaviours to Tolerate Neuropathy?

Today's post is based on the findings of a study of self-care for symptoms of HIV (see link below). It basically shows that a significant number of HIV-patients with neuropathy will turn to so-called 'unhealthy behaviours' to tolerate the worst aspects of neuropathic pain and discomfort. This is a very interesting premise you may not have thought too much about. Do you subconsciously or consciously smoke more, drink more, or use recreational drugs to mask the symptoms? Do you maybe self-overdose on the prescribed medications, in the hope that more means a better result...especially if they don't seem to be working? No one is judging here; sometimes desperate times call for desperate measures and nobody needs to tell you that what you do is not good for your health in one way or another - that's a given but if it helps...

With an illness that has no cure and symptoms which are extremely difficult to control, it's probably little wonder that people turn to any means possible to make life more bearable. It's a subject that probably needs much more extensive research, after all, neuropathy isn't the only side effect of HIV and we may be surprised to learn how widespread 'unhealthy behaviours' actually are.

Unhealthy behaviours for self-management of HIV-related peripheral neuropathy.
by Nicholas PK, Voss JG, Corless IB, Lindgren TG, Wantland DJ, Kemppainen JK, Canaval GE, Sefcik EF, Nokes KM, Bain CA, Kirksey KM, Eller LS, Dole PJ, Hamilton MJ, Coleman CL, Holzemer WL, Reynolds NR, Portillo CJ, Bunch EH, Tsai YF, Mendez MR, Davis SM, Gallagher DM.

The prevalence of peripheral neuropathy is frequent in HIV disease and is often associated with antiretroviral therapy. Unhealthy behaviours, particularly substance-use behaviours, are utilized by many HIV-positive individuals to manage neuropathic symptoms. As part of a larger study on self-care for symptoms in HIV disease, this study analyzed the prevalence and characteristics of unhealthy behaviours to self-manage peripheral neuropathy in HIV disease. Sociodemographic and disease-related correlates and unhealthy behaviours were examined in a convenience sample of 1,217 respondents who were recruited from data collection sites in several US cities, Puerto Rico, Colombia, and Taiwan. Results of the study indicated that respondents with peripheral neuropathy identified a variety of unhealthy self-care behaviours including injection drug use, oral drug use, smoking cigarettes and alcohol ingestion. Specific unhealthy behaviours that participants reported to alleviate peripheral neuropathy included use of marijuana, smoking cigarettes, drinking alcohol and street drugs. A subset of those individuals, who identified high levels of neuropathy (greater than five on a scale of 1-10), indicated significantly higher use of amphetamines and injection drug use in addition to alcohol use and cigarette smoking. For participants from Norway, substance use (using alcohol: was one of the most frequent self-management strategies. Implications for clinical practice include assessment and education of persons with HIV for self-care management of the complex symptom of peripheral neuropathy.

Friday, 25 November 2011

Sexual Problems for Men with Neuropathy

This is another topic which has been covered before on the blog but recently a 50 year old man from Arkansas mailed and said that despite having both neuropathy and HIV for some years, his doctor had told him that his erectile disfunction was a result of his age and a lifetime of smoking, nothing more. This may perhaps be the case but some doctors need to realise that ED can definitely be a result of neuropathic complaints and not dismiss someone's concerns with a cliche. Losing their potency is a really big deal for many men and having a genuine medical reason for it can perversely, ease the blow. This article is from (see link below) and shows the link between ED and neuropathy revealed by the results of Spanish research in this area.

Erectile dysfunction study shows high prevalence of peripheral neuropathy
November 15, 2011

Spanish researchers have uncovered clear links between erectile dysfunction (ED) and peripheral neuropathy, according to a paper in the December issue of the urology journal BJUI.

"Up to now the impact of damaged nerves in the peripheral nervous system on ED has been underestimated" says lead author Dr Consuelo Valles-Antuña, from the Department of Neurophysiology at the Hospital Universitario Central de Asturias in Oviedo.

"However our study of 90 patients shows that men with more severe symptoms of peripheral neuropathy, which can be caused by disease, trauma or illness, had greater self-reported ED and required more aggressive treatment.

"Our findings underline the importance of clinicians carrying out neurophysiological tests on patients with ED, particularly in the pelvic area."

The research team, which included experts on both neurophysiology and urology, studied 90 consecutive patients with sexual problems recruited from the hospital's Department of Andrology.

ED was diagnosed using the five-item version of the International Index of Erectile Dysfunction (IIEF-5) and the occurrence of peripheral neuropathy was predicted using the Neuropathy Symptom Score.

A range of neurophysiology tests were carried out to assess the presence of large and small fibre peripheral neuropathy.

The researchers found that:

•The average age of the men in the study was 54 years of age. Ten per cent were under 40 and only two per cent were over 70.
•No significant correlation between IIEF-5 scores and increasing age was found. In fact, younger patients had lower (worse) IIEF-5 scores, which could be due to higher expectations or a higher number of organic risk factors.
•Just under a third of the patients (30 per cent) had cardiovascular disease, 16 per cent had neurogenic risk factors (relating to the nerves or nervous system) 16 per cent had diabetes and 11 per cent had no risk factors. Just over seven per cent had been diagnosed with mental health issues.
•Patients with more severe symptoms of peripheral neuropathy showed lower (worse) IIEF-5 scores and required more aggressive therapies.
•Neurophysiological exploration confirmed that just under 69 per cent of patients had neurological pathology. Of these, 61 per cent had some type of peripheral neuropathy and eight per cent had myelopathy - problems with their spinal chord.
•Just under 38 per cent of the patients had polyneuropathy, which occurs when a number of the peripheral nerves throughout the body malfunction simultaneously. Of these nine per cent had small fibre neuropathy, damage to the small unmyelinated peripheral nerve fibres, and just over 14 per cent had pudendal neuropathy, affecting the somatic nerve in the pelvic region.
•The findings of the sympathetic skin response tests underlined the importance of checking nerve problems in the pelvic area, as response alterations were much more common in the penis than hand or foot.
•No association between neurophysiological diagnosis and IIEF-5 scores was detected, but a statistical association was found between neuropathy and the Neuropathy Symptom Scores.
."To our knowledge, this is the first study to assess the whole peripheral nerve fibre spectrum in a non-selected group of patients with erectile dysfunction" says Dr Valles-Antuña.

Thursday, 24 November 2011

B Vitamins, Alpha Lipoic Acid and other Nutrients for Neuropathy

There have been other posts on the blog (see alphabetical list on the right) about both Alpha Lipoic Acid and nutrients in general which may or may not help with neuropathy. Today's post comes from MDJunction (see link below) and is an excellent account, though without any indication of the writer's qualifications. That said, she says nothing that isn't found on most related sites on the Web (and provides more detail than most) and that may, in your opinion, be verification enough.
The general concensus from neurologists is that they support B-Vitamins and both Alpha Lipoic Acid and Acetyl-L Carnitine as supplements which may improve neuropathic problems but you should be aware that neither is cheap and in most countries, neither is covered by any sort of insurance policy. If the case is proved, it seems unfair to discriminate on the basis of who can and who can't afford a treatment but that's a whole other story!
Also, always take extra B-vitamins with advice from your doctor - it's easy to create an imbalance in your body and cause more harm than good.
If you decide to try supplements, (after consultation with your doctor) shopping around on the Net may help reduce costs.

Peripheral Neuropathy- Nutrients
Mar 23 2011

Neuropathy: Nutrient Therapies

Although there has been virtually no research on the use of nutrient therapies for HIV-related neuropathies, there has been a fair amount of research (mostly in other countries) on their use for diabetic neuropathies. Since it appears likely that at least some of the mechanisms for the nerve damage may be similar in the two diseases (inflammation and oxidative damage to the nerves combined with B vitamin deficiencies), there is reason to believe that therapies which have proven useful for diabetics may also work for at least some people living with HIV who develop neuropathy. Many people living with HIV have reported to me that they have successfully eliminated neuropathy with some combination of the nutrient therapies discussed here. Thus, in addition to the other treatments mentioned, I would stress the importance of therapy with the B vitamins and other nutrients, especially acetyl-L-carnitine, gamma-linolenic acid, alpha-lipoic acid, magnesium, and chromium. I would definitely consider including the nutrients that have been shown to help rebuild the myelin sheath around nerves and/or improve nerve functioning such as choline, inositol, gamma linolenic acid, B6, B12, niacin, thiamine, biotin, folic acid, and magnesium.

Biotin, choline, inositol, and thiamine are B vitamins that have all been found useful in treating the peripheral and autonomic neuropathies found in diabetes and may also help with HIV-related neuropathies. In a study at the University of Athens, it was shown that regular, long-term use of biotin in diabetics was very effective both for improvement in nerve conduction and relief of pain. Improvement in nerve conduction occurred after only 4-8 weeks of therapy. In this study, biotin was given via daily intramuscular injection (10 mg/day) for 6 weeks; then 3 times per week (10 mg), intramuscularly, for 6 weeks; then 5 mg/day taken orally for up to two years. The researchers hypothesize that deficiency, inactivity, or unavailability of biotin in diabetics may result in disordered activity of the biotin-dependent enzyme, pyruvate carboxylase, leading to an accumulation of pyruvate and/or a depletion of aspartate, either of which could adversely affect nervous system metabolism. There are a number of reasons why HIV-positive persons may be deficient in biotin and, thus, potentially at risk for a similar problem. It has been suggested that those with neuropathy symptoms might try 10-15 mg/day orally, taken in conjunction with the other B vitamins found useful for improving nerve function.

B12 deficiency is a known cause of neuropathy so this vitamin, along with its coworker folic acid, should certainly be included in any program aimed at eliminating this symptom. Typical symptoms of peripheral neuropathy related to B12 deficiency include the type of leg and foot pains experienced by many. B6 deficiencies are also known to cause both carpal tunnel syndrome (with symptoms of numbness, tingling, and pain in the hands and wrists) and degeneration of peripheral nerves and may be responsible for some peripheral neuropathy problems.

Choline and inositol also seem to be very important parts of the combination of vitamins needed for neuropathy resolution. Diabetic neuropathy is known to be associated with a reduction in myo-inositol levels in nerves and tissues. The decreased level of myo-inositol is believed to cause a decrease in the activity of the sodium-potassium pump and, thus, to change the sodium permeability of nerves. Both diets high in inositol and inositol supplementation have been shown to improve diabetic neuropathy. Researchers at the University of Alabama found a statistically significant improvement in nerve function in diabetics placed on a diet high in inositol. Included in the diet were high-inositol foods such as cantaloupe, peanuts, grapefruit, and whole grains. Other researchers have reported that supplementation with inositol in doses of 2-6 grams per day has resulted in improvements in neuropathy. Robert Atkins, M.D., has reported his successful use of 2-6 grams per day for reversing diabetic neuropathy, and notes that physicians at St. James Hospital in Leeds, England, have reported good results with even smaller dosages.

In addition to the use of inositol itself, treatment with acetyl-L-carnitine can help raise nerve myo-inositol content. Florida researchers have found that peripheral nerve function in diabetes is linked to nerve myo-inositol content and that acetyl-l-carnitine can raise the levels of myo-inositol in the nerves of animals with experimentally induced diabetes. It also apparently protects the nerve membranes from free-radical damage, as evidenced by reduced malondialdehyde levels in the animals treated with acetyl-l- carnitine.

Thiamine has also been seen to be useful in treating diabetic neuropathy. Stanley Mirski, M.D., has reported that a large percentage of his diabetic patients who suffer from neuropathy have achieved improvements with daily thiamine supplementation in doses of 50-100 mg. Using a fat-soluble form of thiamine such as thiamine tetrahydro-furfuryl disulfide may be preferable because of the relatively poor absorption of water-soluble forms of this vitamin. This type is contained in Cardiovascular Research's Allithiamine. A large number of HIV-positive people have reported to me their successful elimination of neuropathy with the combined use of the B vitamins discussed here. The information on acetyl-l- carnitine is too recent for much in the way of anecdotal reports to have surfaced, but it might be an important addition to improve the chances for successful elimination of neuropathy.

Alpha-lipoic acid has long been used in Europe for the treatment of peripheral neuropathy in diabetics. A number of controlled clinical trials have shown its usefulness for reducing both the pain and numbness suffered by those with diabetic neuropathy, and its use for this condition is approved in Germany. Its antioxidant properties may help protect the nerves from the inflammation and oxidative damage that HIV induces, as has been shown to be true with diabetic neuropathy. Because of its liver protective and antioxidant benefits, it has been included as a component of the programs of many of my clients for several years now. It may have contributed to the success of the neuropathy elimination programs some of them have used.

Gamma linolenic acid is an essential fatty acid found in borage oil, grape seed oil, black currant oil, and evening primrose oil that has been shown to be successful in reversing nerve damage in diabetics suffering from peripheral neuropathy. In a double-blind, placebo-controlled study using 480 mg of GLA daily, all the diabetics given the fatty acid experienced gradual reversal of nerve damage and improvement in the symptoms related to the peripheral neuropathy, while those on placebo gradually worsened. It is thought that GLA may help to rebuild the myelin sheath around the nerves, thus restoring proper nerve conduction.

Magnesium is also known to be necessary for nerve conduction; deficiency is known to cause peripheral neuropathy symptoms. Thus, including optimal amounts of magnesium might contribute to elimination of neuropathy. There have also been reports of chromium deficiency causing peripheral neuropathy. I learned this too recently for chromium to have been included in most of the neuropathy therapy programs used by my clients in the past and, thus, I'm not sure what it might contribute. However, chronic infection is known to deplete body stores of chromium, so adding a dose of perhaps 200-400 mcg/day to a complete nutrient protocol might be reasonable.

In addition to all the nutrient supplements, an analysis of data coming out of the Immune Enhancement Program in Portland, Oregon, appears to show that their program, which includes Chinese herbs along with acupuncture and various other therapeutic approaches, results in improvement in neuropathy for some.

If you are considering supplementation with any of the B vitamins discussed above, never forget that although B vitamins are by and large non-toxic, any individual B vitamin should always be taken along with the full B complex to prevent imbalance in the body. Long-term use of very high doses of individual B vitamins taken alone, without the rest of the B complex, can induce imbalances or deficiencies in other B vitamins.

About Alpha Lipoic Acid

Alpha-lipoic acid (ALA), also known as lipoic acid (or thioctic acid), is a sulfur-containing fatty acid found inside every cell of the human body. The main function of alpha-lipoic acid is to generate the energy required to keep living organisms alive and functioning. Lipoic acid plays a key role in a variety vital energy-producing reactions in the body that turn glucose (blood sugar) into energy.

Alpha-lipoic acid is a potent biological antioxidant that has been shown to slow the oxidative damage in cells, and in many cases stabilize or even reverse cell damage. Alpha-lipoic acid is so effective as an anti-oxidant because it works on both water and fat-soluble free radicals that cause oxidation and cell damage in the body. Notwithstanding its popularity, the exact mechanism responsible for the medicinal affects of alpha-lipoic acid is still not fully understood.

Some research suggests that certain nerve diseases may occur as a result of free radical damage. Since alpha-lipoic acid can reach all parts of a nerve cell it can potentially protect nerve cells against such damage. This is the rationale behind studies on the potential benefits of alpha-lipoic acid for diabetic neuropathy.

Experimental studies show that alpha-lipoic acid may exhibit a renal protective effect in individuals with diabetes. Alpha-lipoic acid increases glucose uptake in the cells and appears to reduce symptoms of diabetic complications including cataract formation, vascular damage, and polyneuropathy (nerve damage). A study published in Diabetic Medicine in 1999 showed that patients treated with 600 mg of ALA 3 times daily for 3 weeks had improvement of diabetic symptoms from polyneuropathy. In another study using 600 to 1,800 mg of ALA daily, individuals treated showed improved insulin sensitivity. Most studies supporting the use of alpha-lipoic acid to reduce symptoms of diabetic peripheral neuropathy employed intravenous alpha-lipoic. Evidence for the use of oral lipoic acid, in connection with diabetes remains weak and contradictory.

Another group of nerve cells in diabetics, the autonomic nerves, which control the function of internal organs, may also become damaged. When this same phenomenon occurs in the heart, a condition known as cardiac autonomic neuropathy, it leads to irregularities of heart rhythm. There is some evidence that alpha-lipoic acid may be helpful for this condition.

Some in the scientific community believe that alpha-lipoic acid can actually reverse the damage in aging cells of the brain. Alpha lipoic acid has also been used both in oral and topical forms as a way for keeping skin healthy and young in appearance. There have been studies documented in medical literature indicating that supplemental ALA may even be beneficial in patients with glaucoma. is a great consumer resource that collects user reviews for alpha lipoic acid products.


The common dosage of alpha-lipoic acid for complications of diabetes is 100 to 200 mg three times daily. In studies that found benefit of supplementing with alpha-lipoic acid, several weeks of treatment were often necessary for effects to develop. However, some studies have indicated as much as 600-1,800 mg per day of alpha-lipoic acid for optimal benefit in people with specific health concerns such as diabetes, liver cirrhosis and atherosclerosis.

If you are healthy and want to promote optimal health, a dose of 30 - 300 mg per day may be sufficient.

Lipoic acid appears to have no significant side effects at dosages up to 1,800 mg daily.

Wednesday, 23 November 2011

Leg Pain - not always Neuropathy

This blog almost always relates HIV-related, foot and leg pain to Neuropathy but that's not always the case and it's always worth bearing in mind that there are other possible causes, before jumping to conclusions. When you're HIV positive, it's easy to pin a label on a problem at the first sign of trouble, after all, when it comes to secondary infections, virus, or drug related conditions, we're prone to almost everything (and they wonder why some people become hypochondriacs!) This article from (see link below) outlines the commonest causes of leg pain. The true cause will eventually be discovered by your doctors but keeping an open mind before you get the diagnosis weeks or months later, is always advisable.

Leg Pain
May 21, 2011

In addition to injuries and muscle cramps, various medical conditions can cause leg pain. This article covers some of the medical conditions that can cause leg pain. Medical conditions involving the cardiovascular system will be discussed in a separate article in this series about leg pain.

Peripheral neuropathy is not a disease in itself, but a symptom of nerve damage in the limbs that is caused by other medical conditions. Peripheral neuropathy is common in patients with diabetes, HIV/AIDS, vitamin B12 deficiency, cancer, lupus, syphilis, lyme disease, rheumatoid arthritis, sarcoidosis, hypothyroidism, toxic exposure, certain genetic diseases and so on. Peripheral neuropathy is a common symptom and it can be inherited, caused by an infection, caused by exposure to certain chemicals, experienced as a side effect of some medications, caused by metabolic disorders or nutritional deficiencies, caused by inflammatory diseases, caused by oxygen starvation or caused by trauma to a peripheral nerve.

Peripheral neuropathy commonly affects the feet and legs. If a nerve that carries sensation from the body to the central nervous system is damaged, a person may experience pain, burning, numbness or tingling in the leg or foot. Proprioception, or the ability to sense where a body part is without looking, can also be affected and a person can become more uncoordinated. If a motor nerve that supplies a muscle is damaged, a muscle becomes weak because it can not contract as well. It is possible for some muscles to become paralyzed, depending on the extent of the nerve damage. In some cases, muscles may cramp up instead of becoming flaccid and weak. Treatment of peripheral neuropathy involves treating the underlying cause of the problem, along with symptomatic care for pain and physical or occupational therapy if necessary.

Another possible medical cause of leg pain is a bone infection, called osteomyelitis. Osteomyelitis is a bacterial infection that can be caused by several different types of bacteria. People can contract a bone infection via a wound, such as when an open fracture occurs or when a person has surgery, or an infection can spread to the bone from a different part of the body. A type of skin infection called cellulitis can spread to underlying tissues and bones in the leg, or an internal infection like a bladder infection can spread to other parts of the body through the bloodstream.

Any patient with a suppressed immune system due to aggressive immunosuppressive therapy or an immune deficiency like HIV/AIDS is more likely to develop infections, including osteomyelitis. Treatment for osteomyelitis includes antibiotic medications to get rid of the infection and medications to control pain. If the infection is not treated early, it is possible for the infection to spread to other tissues in the leg, making amputation of the leg necessary. It is also possible for a person with an untreated infection to go into septic shock when the bacteria infect the bloodstream.

If your leg pain is in your joints, you may have arthritis, or joint inflammation. There are many different types of arthritis, including osteoarthritis, gout and rheumatoid arthritis. More information about the various types of arthritis can be found at Infections in the joint capsule itself can also cause joint pain. Osteoarthritis, the most common type of arthritis, is caused by “wear and tear” on the cartilage of the joint. Rheumatoid arthritis is an autoimmune disease. Gout is caused by having too much of a substance called uric acid in your body, which builds up in the joints and causes pain and inflammation. Common symptoms of many different types of arthritis include joint pain, joint stiffness or decreased joint mobility and joint swelling. Treatment for arthritis varies depending on the type of arthritis. Talk to your doctor if you think you may have arthritis pain.

Fibromyalgia is a medical condition that can cause muscle pain in the legs and in other parts of the body. In addition to muscle pain, people with fibromyalgia may also have chronic fatigue, sleep disorders, tension headaches and mood disorders. The cause of fibromyalgia is unknown, but researchers think that people with fibromyalgia have a lowered tolerance to pain because of abnormalities in the way that their brains process pain signals. Treatment for fibromyalgia is symptomatic and aims to control pain, improve sleep and treat mood disorders. Not all aspects of fibromyalgia can be treated medically; for example, the frustration that a patient with fibromyalgia may feel in not knowing how to deal with chronic pain and fatigue may benefit from counseling.

Peripheral neuropathy, infections, arthritis and fibromyalgia are just a sampling of the medical conditions that may cause leg pain. These conditions are not as common as muscle cramps and injuries, but a good proportion of older people develop some degree of osteoarthritis and peripheral neuropathy can be caused by a variety of medical conditions. Always talk to your doctor if you have persistent leg pain and you do not know what is causing it.

Tuesday, 22 November 2011

Are there factors which increase Neuropathy risk?

In a collaboration, the sort of which should perhaps be done much more widely, medical researchers from universities in Australia, South Africa, Indonesia and Malaysia, looked at the common factors associated with HIV-related neuropathy (see link below). It is interesting to see the often-mentioned influences of height and age being confirmed by their findings. The higher rate of neuropathy amongst Australian HIV-patients for instance, can be put down to the fact that people are taller and live longer in that land than in the others. Hopefully, this sort of research will lead to useful conclusions, especially in the field of gene therapy and adjusted medication based on neuropathy predictions.

Study collaboration in Australia, Asia and South Africa in antiretroviral toxic neuropathy
School of Pathology and Laboratory Medicine - University of Western Australia

Neuropathy (nerve damage in the feet) is a common problem for people living with HIV.

This can be caused by HIV itself, but a clinically similar neuropathy is a common side effect of some older nucleoside analog reverse transcriptase medications (“antiretroviral toxic neuropathy” or ATN). In particular, stavudine is a drug commonly associated with neuropathy.

Stavudine is still used in first-line HIV treatment in many resource-limited settings, so neuropathy is an important problem in Africa and Asia. This project addresses why some patients suffer ATN whilst others do not when treated with stavudine. This will help clinicians decide which patients may be treated safely with stavudine and who should be prioritized for access to alternative drugs. We are investigating whether a simple genetic screen could be used to determine patients’ risk. Future studies will address the underlying pathogenic mechanisms to facilitate development of better treatments for this difficult problem.

Disordered inflammation is important in the pathogenesis of HIV neuropathy and may be central to the pathogenesis of ATN. TNF genotypes influence the individual’s risk of ATN following exposure to potentially neurotoxic NRTI such as stavudine (Cherry et al, 2008). We found that alleles of TNFA and IL12B (encoding TNFa and IL-12p40 respectively) distinguished Australian patients who developed ATN within six months of starting these drugs from those who did not. Neuropathy is common among Australians with HIV. Dr Cherry and Jacquita Affandi confirmed that 44 per cent of patients attending one clinic in 2006 are affected (Smyth et al, 2007).

We then enrolled cohorts of HIV patients in Jakarta and Kuala Lumpur, confirming that neuropathy is also common among patients at both of these sites (affecting 34 per cent and 19 per cent respectively). We showed that increasing patient height and increasing patient age are risk factors for ATN – and that the higher rate of ATN in Australian patients compared to similarly treated patients at our South East Asian sites is largely attributable to these factors (Cherry et al, ASHM 2008). Initial genotyping of Indonesian patients confirmed that TNFA-1031*2, an allele associated with ATN risk in Australians, is also a risk factor for neuropathy in Indonesian HIV patients (Affandi et al, 2008).
Further patients are now being recruited, including South African HIV patients in Johannesburg. Our collaborators (Antonia Wadley and Dr Kamerman) report that neuropathy is common in their clinics. If the algorithm developed in Australian and Asian patients is confirmed in this group, it will constitute a robust tool to assess HIV patients’ risk of ATN before they start treatment. This will aid rational drug selection, especially in clinics where some use of stavudine remains an economic necessity. An improved understanding of how cytokines and inflammation are involved in ATN may also allow future development of immunotherapeutic strategies to treat this disabling problem.

Constance Chew (PhD student, UWA) has now joined the project to characterise TNF Block haplotypes associated with neuropathy in patients from Australia, Indonesia, Malaysia and South Africa (Chew et al 2008).

Monday, 21 November 2011

Dilemmas concerning Neuropathy treatment

Today's post is another worthwhile video from (see link below) in which you can hear a realistic assessment of the effectiveness of current neuropathy treatments by a clearly well-qualified expert. Professor Simpson's message is not exactly encouraging but may help you make the best decisions when confronted with the choice of beginning certain accepted treatments or not. You may be surprised to learn that several medications have been proved to have no more effect than a placebo but are still routinely prescribed for neuropathy because they fit into the sequence of 'what we must try' in the medical texbooks. Taking the potential side effects into account may help you decide whether to go ahead or not. Although a good discussion with your specialist is always advised, it may help to show your doctor this videoclip, (or other posts from the blog on the same subject). It is important not to feel bullied into something you're not completely comfortable with.
The text above the video is the introductory text that accompanies it on the site.

Neuropathic Pain in HIV Disease

David M. Simpson, MD, Professor of Neurology at Mount Sinai School of Medicine, New York.

Peripheral neuropathy is one of the most common neurologic complications of HIV. In fact, nearly 50% of HIV patients are thought have signs of neuropathy, with increased risk in those with advanced disease. Assessment and treatment of these patients can be complicated by antiretroviral agents, which themselves are often neurotoxic. Neurologic effects may be cognitive, such as impaired memory or vision, and/or sensatory, including numbness, tingling, and pain. Electromyography and skin biopsy may assist in a diagnosis. Attempts at regenerative therapy have not yet proved effective, and treatment of HIV-associated peripheral neuropathy is primarily symptomatic. Of note, placebo-controlled clinical trials of some analgesic agents that are traditionally used to treat neuropathic pain have failed to show significant benefit. Some clinical success, however, has been demonstrated with lamotrigine, gabapentin, and a new high-concentration capsaisin patch. Here, Dr. Simpson discusses current barriers to treatment and available therapeutic options in this challenging disease.

Sunday, 20 November 2011

Pain from Neuropathy: Development and Treatment

This article from (see link below)is intended for health professionals and discusses the theories behind chronic neuropathic pain; why it happens and how it affects people's lives. It does no harm to have an idea of what your doctor may be thinking, when you arrive in the surgery complaining about neuropathic pain and as their thoughts may well be influenced by 'advisory' documents like this one, you may be able to better formulate your story, having some knowledge of the theory behind your problem. With this sort of background knowledge, the appointment could be much less one-sided and much more constructive than if you were going in blind. One would hope that there are very few first-port-of-call doctors left, who still tell you that it's mostly between your ears and there's nothing that can be done but if you're unfortunate enough to meet one who dismisses your symptoms, then this sort of article will provide you with the evidence to stand your ground.

Neuropathic Pain, Development & Treatment
Dr J C D Wells

Pain hurts! Recent functional Magnetic Resonance Imaging (fMRI) shows that most people who complain of chronic pain have very significant activation of part of the brain which lights up as a result of acute pain from experimental injury. It is now accepted by scientists and pain relief specialists that chronic pain is a condition in its own right and is often mediated by changes within the central nervous system, leading to activity in the limbic system which produces an unpleasant sensory and emotional disturbance. The amount of physical insult needed to promote unpleasant pain diminishes with chronicity so that patients experience both hyperalgesia, that is, severe pain on being provoked with normally mildly painful stimuli, and allodynia, which is pain being produced by normally non-painful stimuli, such as stroking or touching. We know and see these events in conditions such as post-herpetic neuralgia and post nerve injury, but it is becoming increasingly clear that these phenomena also occur in some patients with chronic back pain, fibromyalgia and similar chronic conditions.

Of course there are still those who malinger, that is, consciously complain of pain when none exists, in order to receive financial advantage, sign off work and the like, and it is difficult to distinguish sometimes between these and the genuine chronic pain sufferer, but just because there is no significant amount of physical disease at the time of examination, this does not mean that the patient is not experiencing real pain. The aforementioned fMRI shows that patients who have pain as a result of psychological and psychiatric disturbances (for example, depression or somatoform disorders) also feel and experience disturbances in the same part of their brain as the acute pain sufferer, the limbic system; ie, they are suffering from pain.

The limbic system not only experiences pain but also handles fear, anxiety, sleep, punishment and autonomic changes. It affects tension, which in turn affects the intensity of pain. Recent studies on antidepressants show that these produce regrowth of parts of the limbic system which have degenerated becuase of depression, further cementing the relationship between pain and depression and the response of pain to antidepressants. The complex nature of the sensation of pain was first appreciated by Melzack and Wall, who described the gate control theory of pain in the late '70s. At first their work was contested, but there has been gradual appreciation that pain is greatly attenuated both in the spinal cord and in the brain, and if there is lack of attenuation can lead to very severe and unremitting pain in the absence of significant nociception.

Throughout the last decade, the notion of central sensitisation and wind-up occurring as a result of repeated tissue or nerve damage, has been appreciated. This leads to a decreased threshold of peripheral stimulus, an expansion of the receptor field and increased spontaneous nerve firing. This, combined with the sensory aspect of pain, this modification by social and economic issues, makes pain very difficult to understand and to treat.

The neuromatrix in the limbic system is initially shaped by genetic programming and later by sensory input and experience. At the end of this process, the neuronal signature of each individual appears, not only affected by genetic, sensory and pain experiences, but also by cognitions and by chronic physical and psychological stress. There are major sex differences and gene therapy will probably become an important part of the treatment of chronic pain in the long term. As well as the limbic system, there are at least 25 other areas of the brain that are involved in pain, its transmission and ramifications, and further work is ongoing!

In the peripheral nervous system, if there is nerve damage, damaged axons sprout and form collateral nerve endings and areas which can be damaged or stimulated with light touch. Sodium channels become over-active and nociceptors become sensitised. Sleeping nociceptors, which are usually inert, awaken; basal cell firing increases, wallerian degeneration occurs and sympathetic fibres invade the dorsal root ganglia and sensitise the gate allowing the throughput of pain.

In the central nervous system, activity-dependent sensitisation occurs, plasticity (reorganisation of cortical representation) and disinhibition in the dorsal horn appears through descending pathways from the cortex. An adaptive process takes place throughout the neuraxis (brain and spinal cord) and in the dorsal horn, new pain fibres sprout.

It is not generally realised that pain causes greater negative effects on the quality of life than many other conditions. A report by Sprangers et al in the Journal of Clinical Epidemiology (Sprangers et al, 2000) reports quality of life more affected by musculo-skeletal conditions than renal disease, cerebro-vascular, neurological, gastro-intestinal and even cancer. Pain affects every aspect of a human's life, mood, activity, sleep, independence, fitness, social life and family life. Chronic pain patients become physically and psychologically impaired, overweight, unfit, depressed and anxious. They become socially disadvantaged and lose social contacts.

The cost of pain to the economy is immense. Not only is there a direct cost to the family (estimated at over £10,000 per year) but there is also a cost to the Health Service (£6,000,000,000 per year) as well as social security, unemployment benefits and the like (Sleed and Eccleston,2005).

Pain treatment. Happily there now exist a number of effective treatments for neuropathic pain, and evidence is emerging that these can be useful for chronic pain conditions such as back pan and fibromyalgia, as well as the conditions we understand as being neuropathic, such as post-herpetic neuralgia and diabetic neuropathy. The number needed to treat is a treatment-specific measurement used for relative efficacy comparisons of medication versus placebo. For instance, a NNT of 2 means 50 out of 100 patients achieve more than 50 per cent pain relief because of the treatment, rather than a placebo reaction. We have to remember that NNTs for statins are about 20 and for gastro-protection are about 40 in order to appreciate the usefulness of treatments for neuropathic pain, where the NNTs range from 2 to 5. The lower the NNT, the better the drug.

Symptoms of neuropathic pain. The pain can be burning, shooting, stabbing or sharp. Hypersensitivity is common, including severe pain on mild painful stimuli and spontaneous pain with touch. Neuropathic pain is often seen in patients after shingles, with diabetic neuropathy and with complex regional pain syndromes. The pain can occur post-surgically, with trigeminal neuralgia and with multiple sclerosis.

Pain treatments for neuropathic pain. The most effective treatments for neuropathic pain have been shown to be tricyclic antidepressants (NNT = 2) and opioids (NNT = 2). Pregabalin and Gabapentin come out with an NNT of about 4. Lidoderm patches, which will become available in the UK next year, have a NNT of 2 to 4. Tramadol has a NNT of 4; Capsaicin, which will also be available as a patch in the UK before long, has a NNT of 6 and SSRIs have a NNT of 6+. All of these are good treatments.

However, of course the problem here is one of side-effects. Many of these drugs have significant side-effects; the NNH (number needed to harm) of tricyclics is 6, of opioids 8, of gabapentinoids 12, of Tramadol 15, Capsaicin 10 and of SSRIs 20. The safest by far is the Lidoderm patch, with a NNH of 40 - but guess what? It will cost more than the others! Thus treatment choices are going to be a balance between efficacy, which most of them have, side-effects, which most of them produce and cost, and remember that the newer ones are nearly always more expensive. In fairness, they have to be, because the pharma company has to reclaim its development costs.

In an algorithm described in the journal "Pain" in 2005, Finnerup recommended that Lidoderm patches should be used whenever there is allodynia and hyperalgesia; otherwise, patients should be commenced on tricyclics unless there is a specific contra-indication, when they should be commenced on Gabapentin or Pregabalin. The pair can be used in combination, but if there is failure due to lack of effect, or more likely due to side-effects, Tramadol and stronger opioids can be introduced. There is a relative chance of cholinesterase syndrome if high doses of tricyclics and Tramadol are used together, but in practice this is unusual. Most patients with neuropathic pain can be treated successfully with this simple algorithm;

Pain Clinics are usually glad to see patients where success has not been achieved, as often further medication changes, or the addition of other specific treatments, for instance, nerve blocks or Pain Management Programmes, can be successful in reducing pain and increasing activity

Saturday, 19 November 2011

Modern Drugs and Neuropathic Pain

The article in today's post comes from (see link below) and is a very clear and easy to follow, summary of standard neuropathy treatment over the last ten years. I say 'ten years' with some confidence because the article was written in June, 2001 and was published as 'current thought' on this website (as well as many others) in November, 2011. What is slightly shocking is, that compared to for instance, the development in HIV drugs (another notoriously difficult research area), neuropathy treatment seems to have more or less stood still for ten years! Everything in this article is still, surprisingly, true and goodness knows how much money is wasted on ineffective drug treatment. It's claimed that every neuropathy patient reacts differently to different drugs and that is patently true but the number of placebo-controlled tests and studies over the last few years, have shown that several standard-use treatments are effectively worthless. Meanwhile apart from slow developments in the area of gene-therapy and an equally snail-paced, general shift towards capsaicin and cannaboids, nothing else seems to have changed. Everyone must draw their own conclusions but clearly our lobbies in the corridors of drug-development power, are nowhere near strong enough! Nevertheless, this article is useful both as a reference document and a guide for someone new to the disease, who wants to know how he or she will probably be treated anno 2011.

Pain Free: Modern Drugs and Neuropathic Pain
Howard L. Fields, M.D., Ph.D.

During the last millenium, mankind made revolutionary advances in relieving pain. Treatment progressed from non-treatments, such as "biting the bullet," to alcohol and crude opium-based drugs, to the development of safe modern opioids, or narcotic-based painkillers, and a wide range of general and local anesthetics. At least in the developed world, most everyone has found pain relief, at one time or another, from one of these drugs.

Yet despite all our advances, there is one type of pain which, until recently, could not effectively be controlled by modern medicine — neuropathic pain.

Usually chronic and often devastating, neuropathic pain is the result of damage to the body's nervous system. The two most common causes are diabetes ("diabetic neuropathy") and herpes zoster ("postherpetic neuralgia" or "shingles"), an infection of the nerves by the same virus that causes chickenpox. Both cause excruciating pain.

What Does Neuropathic Pain Feel Like?
Although neuropathic pain is highly variable and is felt very differently by different people, doctors can easily distinguish it from other causes of pain. There is usually some abnormality of skin sensation in the painful area and sufferers usually describe neuropathic pain as strange, unfamiliar, often as a burning sensation. It can have a sharpness or a brief shooting quality, as well as a sensation that is described as tingling, crawling, electrical.

Frequently, there is a long delay between the actual nerve injury and the appearance of pain; in fact, it is not unusual for the pain to begin at about the time a person is beginning to recover physically.

Treating Neuropathic Pain
The main problem with treating neuropathic pain is that the standard array of non-narcotic analgesics [acetaminophen, aspirin, non-steroidal anti-inflammatory agents (NSAIDs and cyclooxygenase 2 inhibitors)] have little effect on neuropathic pain. Recently, however, several different classes of drugs have been developed that do help people suffering from neuropathic pain. These are:

Tricyclic antidepressant drugs, or TCAs, are the most extensively studied treatments for neuropathic pain. The most commonly prescribed TCA is amitriptyline. While effective, this drug does have significant side effects, including a type of low blood pressure called orthostatic hypotension. Other side effects include urinary retention, memory loss, heart problems and drowsiness. Because of these significant and potentially serious side effects, doctors normally start patients on a very low dose and increase the dosage slowly.

Desipramine, another TCA, appears to be almost as effective as amitriptyline in most studies, but with fewer side effects and significantly less drowsiness.

For most types of neuropathic pain, selective serotonin reuptake inhibitors (SSRIs) are significantly less effective than TCAs, although the SSRI, paroxetine, has been reported to help pain caused by diabetic neuropathy. On the other hand, SSRIs have virtually none of the side effects of desipramine or amitriptyline, and are non-sedating, that is, they don't cause drowsiness. An added benefit of SSRIs is that they are very effective at treating the depression and anxiety that sometimes afflict those with chronic pain.

Newer Drugs
Though still under study, one of the newer generation antidepressants, venlafaxine (sold under the brand name Effexor®), is a promising drug for neuropathic pain control. Like the SSRIs, venlafaxine is safer than TCAs but acts in a similar way to TCAs and, thus, seems to be more effective than other SSRIs for pain relief.

Anti-seizure drugs, phenytoin (Dilantin®) and carbamazepine (Tegretol®), are effective in treating pain caused by a cranial nerve disorder called trigeminal neuralgia (also known as tic doloreux). Unfortunately, most of these drugs do not seem to help with other types of neuropathic pain. An exception is gabapentin (Neurontin®), which does appear to be effective against a broad spectrum of neuropathic pains, including postherpetic neuralgia and diabetic neuropathy. Many pain specialists are now using gabapentin as a first line drug for neuropathic pain because it is safe and has few unpleasant side effects other than sedation.

Anesthetics and Antiarrhythmics
The local anesthetic lidocaine, given I.V., brings significant relief to those suffering from postherpetic neuralgia and some other neuropathic pain syndromes.

Certain drugs designed to treat irregularities of heart rhythm ("anitarrhythmics") work in a similar way to lidocaine and are being used to treat some types of neuropathic pain. These drugs include tocainide (Tonocard®) and mexiletine (Mexitil®). Mexiletine is less toxic and has been shown to be effective for pain caused by diabetic neuropathy and other neuropathic pains. Currently, it is used as a third line drug after TCAs and gabapentin. The main side effect of these drugs is gastrointestinal problems, although these can be managed with antacids or other "upset stomach" medications.

Opioids, or Narcotics
We live in a culture in which opioid, or narcotic, drugs are associated with moral, political and legal controversy. Until recently, there was wide disagreement, even among pain experts, over whether opioid painkillers should be given to those with chronic neuropathic pain.

Recent studies, however, have made it clear that opioids can safely relieve many types of neuropathic pain. These drugs include morphine, fentanyl, oxycodone and tramadol. As effective as they are, the potential risk for addiction or abuse is something that both doctors and patients need to keep in mind. Anyone starting on opioids should be very careful to follow their doctor's instructions and use the drugs exactly as directed.

Topical Medications
Topical medications, a category of drugs designed to be applied externally, rather than injected or swallowed, are most commonly used in cases of postherpetic neuralgia.

One example is capsaicin extracts. Found naturally in peppers and other members of the deadly nightshade family, capsaicin is commercially available in two forms, Zostrix® and Zostrix-HP® While some studies have found it somewhat effective, many patients stop using it before it begins to work because capsaicin can produce a burning sensation.

A more useful topical medication for neuropathic pain, especially for shingles, is the local anesthetic lidocaine (see above). Available in patch form under the brand name Lidoderm®, it is very safe and convenient. And the lidocaine patch has the added benefit of providing a barrier which helps protect an area of hypersensitive skin.

Treatment Plan
The ideal in medicine is to treat the cause of a disease rather than its symptoms. Unfortunately, for patients with painful nerve injuries, this is often not possible. The majority of patients require some type of medical pain management.

Depending on the individual case, the first step is to try the topical local anesthetic patch, Lidoderm®. If local treatments do not work, doctors generally move on to one of the tricyclic antidepressants (TCAs). If these are not effective, or if there is a problem with side effects, the next step is to try gabapentin, sometimes in combination with a TCA. If patients still have significant pain, doctors may then prescribe antiarrhythmics.

Finally, if all other options have been tried and failed, the last resort is to give patients the milder opioid, tramadol. If that does not work, then the more powerful opioids are used, often in combination with a TCA or other drug.

While neuropathic pain is often difficult to treat, new medicines and better approaches are now available. Research in this field is active and promises to provide further improvements in the near future.

Dr. Fields is Professor of Neurology and Physiology, and Director, Wheeler Center for the Neurobiology of Addiction, University of California, San Francisco.

In the past three years, Dr. Fields has served as a consultant for Neurogen and Endo Pharmaceuticals, and has served on the Speakers' Bureau for Pfizer, Abbott and Merck.

Friday, 18 November 2011

HIV-Related Neuropathy

Today's video is an Australian view of how HIV can cause neuropathy, whether from the virus itself or the drugs. It comes from (see link below) and is basically a teaching video for other medical professionals. The difference with most of the other neuropathy videos posted here on the blog, is that if this is what medical students are learning, then we can look at the disease from the point of view of the doctors who treat us. It seems to be full of up to date information and reflects modern medical thinking but apart from the odd scientific term here and there, which may not be so easily understood, the vast majority of the 11 minutes, is pretty interesting to the average neuropathy and HIV patient and explains a few areas which may have previously seemed vague.

Thursday, 17 November 2011

Truvada and Neuropathy

Today's post comes via Bob Leahy, who has featured on this blog before. He is a contributing editor to, (see link below) a Canadian HIV magazine on-line and has suffered from neuropathy for a long time. His other articles on Positivelight are definitely worth a visit.

There have been various doubts about Truvada (HIV NRTI medication) in the recent past, not least concerning the long term effects on the kidneys but it seems that the drug may also contribute to neuropathic problems. If this is the case, then it joins a growing list of potential medication causes for the disease. Sometimes the science needs to catch up with what's happening on the ground and you won't always be able to rely on drug companies to change their marketing on a highly successful money-spinner. The fact that Truvada is also being suggested as a 'one-a-day' PEP(Post Exposure Prophylaxis) pill, brings all sorts of concerns with it. Kids of twenty who start on something like this and take it every day for ten years or more...I leave you to do the worrying!

Of Truvada, Neuropathy and the state of Health Care in Canada today
by Bob Leahy

Bob Leahy continues the saga of his ouchy feet, with stops on the way for talking about drug regimes. proactive doctors and a report card on how the health care system treats this particular HIVer.

Something very unusual happened to me yesterday. I got a phone call out of the blue from Dr No-Bedside-Manner’s office. (Attentive readers will remember me writing about my experience with Dr NBM here. ) He's my HIV specialist at the Toronto Positive Care Clinic that looks after me.

Actually it was earnest young pharmacist (EYP) placing the call – he works with Dr NBM and had been talking to him - with a suggestion that I drop Truvada from my regime. The reason? It’s potentially contributing to my peripheral neuropathy and also affecting kidney function, according to my blood-work. In fact I have to take THREE drugs to counter side effects of Truvada, which currently brings my HIV arsenal to eight different meds a day. That‘s way too much, in my view.

Anyway, I’ve raised the possibility of dropping Truvada before, but it’s been a no go. Now Dr NBM and EYP seem to have had a change of heart. I’m game of course. Truvada is a drug with an “interesting” profile of side effects, to say the least. I’d say it’s potentially far more troublesome than the oft-quoted villain of the drug cabinet, Sustiva. In any event, I’m happy to flush the things down the toilet – or something. Bye bye Truvada it is.

(Btw, there are blogs/community forums which discuss side effects like this. Here’s one on the Isentress/Truvada combo – I also take Isentress. These forums may work well for some people but I must confess I don’t use them – I’m just not that obsessive.

In any event, the other part of that morning’s phone discussion with EYP involved my peripheral neuropathy issues. I’ve been on Gabapentin just one week, and EYP wanted to know how I was doing. I really don’t know the answer, but I think it might just be showing some improvement. On the other hand, I’m not immune to the placebo effect. The mind is a curious thing. Check back with me in a month and I’ll tell you better how the Gabapentin is working.

But my feet SHOULD be worse. They had their hardest work-out in months this past weekend. I was in Quebec City with my partner and friends and while we took A LOT of cabs, I still ended up walking about 2 km one day. (I have a post on that trip, btw, with a ton of pics, in the works.) Anyway, my feet were pretty raw after that, and I was literally hobbling by the end, but at least I walked 2 km, which is a MAJOR achievement for me.

Trouble is all that hobbling is hard on the body. Your body compensates and you develop achy legs, achy thighs and in my case a truly achy back. Jeez, if it isn’t one thing it’s another.

But the real point I wanted to make is that, back to Dr NBM and EYP, I was bowled over by how proactive they were in phoning me. I mean that clinic is super busy, and these are two busy guys. Amazing really that I’d get a phone call and with a really consultative approach to my options at that. Score one for the Positive Care Clinic peeps.

You know, people complain about the Canadian Health Service A LOT. Come election time it’s often named as the voting public’s number one issue. But the voting public are more likely than not only casual users of the system. As a HEAVY user of the system ever since I was diagnosed eighteen years ago, I’ve seen some amazing things happen. Overall, I’d rate the service one gets quite highly. I once, for instance, went to our local hospital emergency when I had fallen flat on my back on ice. I could hardly move. But I was immediately booked in, went through triage, consultation with a doctor, X-ray and another review with the doctor, this time with X-ray results, all in the space of one hour. True, that’s the exception rather than the rule, but we seldom hear stories like this, and I think our health service get an unnecessarily bad rap. There are so many good people working for us there. In the case of HIV care, even from the publicly financed Catholic hospital I go to (don't ask) my care for the most part has ben respectful, expert and pretty exemplary in every way. I mean they've kept me alive, for starters. My GP, a woman doctor I've dealt with for years now, is an angel too. I’d be interested what other heavy consumers think of the care they receive, though.

So those are the latest developments. Will my feet continue to hurt? What impact will dropping Truvada have. What will Oprah do next? I’ve considered doing regular posts on these topics, my experience with peripheral neuropathy in particular because it’s so common in HIVers, and many who are not experiencing symptoms yet may well do so in time. Plus it’s kind of challenging to treat, and sharing may help. That kind of ongoing coverage sounds like the kind of thing I myself would like to read but could also be seen as incredibly self indulgent. Something to think about, eh?

Wednesday, 16 November 2011

Toughing it out with Neuropathy

Today's post from (see link below) is a hard-hitting personal account of an HIV-patient with neuropathy. It's the sort of story that people without neuropathy may need to read but is difficult reading if you're in the same boat. It's just very close to home for many people and while it's perversely comforting to know that someone else is going through the same thing or worse, it's an uncomfortable feeling to be confronted with the 'what might be' scenario. Don't get me wrong, everyone will have the utmost sympathy for this guy and would do anything to help if they could and like in the old cliche, 'can feel his pain' but it does touch a raw nerve. It highlights how important it is for neuropathy patients to find and keep an effective support system - it's not a disease that's easy to bear alone.

Living with Peripheral Neuropathy
by Chip

I didn’t know, at first, why my feet hurt so bad. I would wake up every 90 minutes or so every night.

Because of the ‘way’ they hurt I thought they were just cold. I tried wool socks. Wore wool socks at work. (Came to find out later heat exacerbates the pain.)

Then one day, sitting in a bar reading a gay-rag advertisement for HIV meds, I saw it. PERIPHERAL NEUROPATHY. That had to be it.

Why didn’t my doctor tell me about possible side-effects I should watch for? Is there some medication that could help? Would I always deal with this pain?

My doctor confirmed the diagnosis and said that some patients deal with the pain anywhere from 6 to 18 months. He explained the reason for the way my brain was ‘sensing’ that my feet hurt. He prescribed an antidepressant that works on nerves that may eradicate the pain.

I was so hopeful! How desperately I needed a full night’s sleep! Well, the medication DID help me sleep but the pain persisted.

After two or three medication trials and a pain specialist intervention, as well as about 10 years later… I still suffer the with pain of peripheral neuropathy. Everyone has heard of a cure, something that helps, how I can deal with this pain. I’m beginning to understand now, that I have become a completely different person because of this pain. Consider for yourself the possibility of a headache or toothache for ten long years. At times I joke that the original antidepressant was prescribed to prevent me from going crazy with this pain.

Don’t doubt for a second that I haven’t considered suicide. I’m not going to make this a long philosophical discussion that has become my life (my HIV status is playing second fiddle now). Everyone listens, everyone cares, everyone hopes and prays for me, people love me, and for that I am grateful.

Someone with a physical abnormality has no way to hide so that people won’t look and wonder or show compassion. Maybe that WOULD actually be harder to deal with on a daily basis than to just be in pain with no one noticing. Maybe I’m the cry-baby now, wanting somehow to make people know about my pain. Funny thing is that when the same people who know of my condition ask "how are you doing?" and I answer "okay", I sometimes want to scream “THEY HURT AS BAD AS ALWAYS AND EVEN WORSE TODAY!”

It would be very easy (let me tell you, very VERY easy) to give up. You may want to as well if you are reading this in between medicating yourself, whether physically, mentally or spiritually. I’m still here. I don’t wanna stick around all by myself. Hang in there. Tough it out with me. Rub some dirt in it. We’ll be OK some day. If not in this world, well for sure in the next…