You're HIV+ and you're getting older...deep sigh, the worst is over but then..!

An article from:www.aidsmap.com

Neuropathy still common in patients with HIV, older age a risk factor
Neurological and cognitive problems
Michael Carter
Published: 14 March 2011


Peripheral neuropathy remains common in patients with HIV, US investigators report in the online edition of AIDS.

Rates of the disease and its symptoms were monitored in over 2000 patients who started HIV therapy between 2000 and 2007.

After three years of therapy, a third of patients had evidence of neuropathy and 9% had symptoms. Older age emerged as an important risk factor for the condition.

“Peripheral neuropathy in HIV patients persists despite improved immunological function and virologic control associated with combination antiretroviral therapy and decreased use of neuro-toxic [drugs],” comment the investigators.

Neurological disorders such as peripheral neuropathy are a well-recognised complication of HIV infection. The virus itself is a cause, and some older anti-HIV drugs such as d4T, ddI and ddC can cause nerve damage. In addition, ageing is associated with a deterioration in neurological function, and some of the co-morbities that are common in patients with HIV, such as diabetes, can also increase the risk of neurological disorders.

Treatments with the antiretroviral drugs with the highest risk of peripheral neuropathy are no longer recommended in resource-rich countries.

However, understanding of the disorder is still imperfect. Therefore US investigators designed a study to assess:

The prevalence of peripheral neuropathy and its symptoms among patients starting HIV therapy.

The risk factors for the disorder and its symptoms.

Predictors of recovery from peripheral neuropathy after stopping therapy with neurotoxic drugs.

Risk factors for neuropathy and its symptoms when taking neurotoxic antiretroviral therapy.

The study included 2141 individuals who were starting antiretroviral therapy for the first time.

They were assessed for peripheral neuropathy using tests that measured ankle reflex and sensation in the big toes. Patients were also asked to report symptoms of the disorder including numbness, pins and needles, and burning sensation.

At baseline, 23% of patients had reduced peripheral sensation or ankle reflexes and 4% reported symptoms associated with peripheral neuropathy.

The patients did well on antiretroviral therapy, and 82% suppressed their viral load below 400 copies/ml and 70% experienced an increase in their CD4 cell count to above 350 cells/mm3.

Three years after starting treatment, 32% of patients had reduced sensation or ankle reflexes, and 9% had symptoms of peripheral neuropathy.

Factors associated with neuropathy were older age (p < 0.001), a low baseline and current CD4 cell count (p = 0.007), use of neuro-toxic antiretroviral drugs (p < 0.001), taller height (p < 0.001), and black race (p = 0.004). Symptoms of the disease were associated with older age (p < 0.001), a low current CD4 cell count (p = 0.01), a higher baseline viral load (p = 0.03), use of neuro-toxic anti-HIV medications (p < 0.001), diabetes (p = 0.001), taller height (p = 0.01), use of statins (p = 0.004), and shorter duration of antiretroviral therapy (p = 0.04). Individuals who ceased taking neuro-toxic antiretrovirals after developing peripheral neuropathy and its symptoms were followed to evaluate their recovery. Over half the patients (54%) continued to have neuropathy and symptoms persisted in 18% of individuals. Taller patients were less likely to recover toe sensation or ankle reflex, and symptoms were more likely to persist in older patients (p = 0.006). Neuro-toxic antiretroviral drugs remain a mainstay of HIV therapy in many resource-limited countries. Therefore the investigators examined the factors associated with the development of neuropathy and its symptoms when taking these therapies. Prevalence of neuropathy among patients taking neuro-oxic therapy was 27% and 9% had symptoms. Older age was associated with neuropathy (p < 0.001), as was therapy with a protease inhibitor (p = 0.003), black race, and a lower CD4 cell count. Symptoms were also associated with older age (p < 0.001), as well as a history of diabetes (p < 0.04), increased height (p = 0.03), and use of a protease inhibitor (p = 0.003). The investigators believe their findings have implications for the future management of patients. They comment, “given the rapidly aging HIV population due to successful therapy, the intersection of aging and increased risk of neuropathy portends ongoing challenges from this complication for HIV therapeutics.” The association between diabetes and neuropathy also concerned the investigators, and they write: “This is a very serious finding given the increasing impact of insulin resistance and diabetes in the setting of HIV infection.” Evans SR et al. Peripheral neuropathy in HIV: prevalence and risk factors. AIDS, online edition, doi: 10.1097/QAD.0b013e328345889d, 2011 (click here for the free abstract).

Sifrol (Pramipexole - Mirapex in the States)

I received this comment from the chairman of a Dutch HIV organisation in the east of the Netherlands. Does anyone else have experience of Sifrol? Let us know.

Hi there !
I am a diabetic (at age 28) and HIV (at age 37) and have experienced Neuropathic pains for over 5 years now (i'm 43).
After much experimenting, I have found much pain relief in a combination of Cannabis and a medicine called SIFROL. Now I hardly experience any pain.
Sifrol is mainly prescribed to patients with Parkinson's, but it also helps a lot with Neuropathic pains !
Sifrol was prescribed for me by my internist, Dr Ten Napel in Enschede, after consultation with my GP.
My experience with Sifrol is that the dose has to be regularly adjusted. You can take up to a maximum of 8 tablets of 0.88mg per day. I began with 3 tablets and when this failed to work, I was given permission to increase it by one tablet. I now take 5 a day. At one point, I was on 7 a day but if the pain is reduced to little or none, you can reduce the dose accordingly.
They work best if you take them one hour before going to bed.

With regards to other parts of this blog and the website, I recognise many of the points made. I too had to fight to be taken seriously and had to literally demand to have something prescribed for the neuropathy symptoms. Ridiculous how many HIV'ers and diabetics are suffering from this disease. I'm the chairman of HIV PlusPunt in Overijssel, a regional initiative voor HIV patients in the area and in that capacity, I also try to advise HIV patients with neuropathy. Some veterans have been walking around for 10 years with unbearable pain and I advise them to ask their doctors about Sifrol and almost all seem to benefit from it.

Robert

Link: http://www.nps.org.au/health_professionals/publications/nps_radar/2009/april_2009/pramipexole

Ooh...whoopee...purple!

Really! Seriously! Another effing ribbon! What possible good will another satin symbol do? Most people can't remember the colour codes for handkerchiefs never mind ribbons! The tragedy is that it comes from probably the biggest neuropathy site on the Net

Neuropathy Awareness Ribbons

Support the neuropathy community by purchasing these new purple ribbons inscribed with "Beat Neuropathy", taken from our tag line, Together, We Can Beat This Disease!

"Beat Neuropathy" implies finding answers, helping a friend understand neuropathy, working with your doctor, promoting awareness, seeking more effective treatments, and, ultimately, finding a cure.

Wear these ribbons--symbolizing neuropathy awareness, the need for critical neuropathy research, and much more--and elevate neuropathy to national consciousness.

Ribbons come in sets of 50 for $15.00.

Visit: http://www.neuropathy.org/ next week to order your set!

The definition of frustration

...is when you look into your friend's eyes and realise what you've deep down, long suspected...they just don't believe you any more...and more to the point, did they ever?

Not surprising but definitely depressing

From the website,The Aids Beacon
I know, many of you are thinking, 'As long as it takes the pain away!' but this article is trying to make the point that the condition of neuropathy itself is very difficult to improve. You can help with the pain but you're not restoring nerve function in the process. In the meantime...more Brownie points for Cannabis apparently!

Most Recommended Treatments For HIV-Associated Sensory Neuropathy Are Ineffective
By Kieryn Graham
Published: Jan 5, 2011 5:17 pm

A review based on several clinical trials has found that most recommended treatments for HIV-associated sensory neuropathy are not effective. Only three pain relievers have demonstrated efficacy against HIV-associated sensory neuropathy: high-dose topical capsaicin, smoked marijuana, and an experimental protein that helps nerves grow.

“Our study is important as it has demonstrated that many drugs which are effective in other neuropathic pain states (and frequently used to treat painful HIV-SN [HIV-associated sensory neuropathy]) have no evidence of efficacy in painful HIV-SN,” said Dr. Tudor Phillips, lead author on the study, in correspondence with The AIDS Beacon.

Dr. Phillips also pointed out that, while the trials in included in the review found that high-dose topical capsaicin is effective, there is also a new trial underway that indicates it may be no more effective than a placebo. He also stated that the nerve growth protein will not be developed further because the required injections are too painful.

“This leaves very few evidence-based treatments available for clinicians to use. Consequently there is a real need to develop new treatment strategies for painful HIV-SN,” he added.

The authors suggested that one promising treatment for this condition may be the drug Cymbalta (duloxetine). Cymbalta is an antidepressant that is also used to treat diabetic neuropathy, a condition similar to HIV-SN. They also recommended that further studies be conducted with pain relievers in the opioid class, which includes drugs such as morphine, oxycodone (OxyContin), and hydrocodone.

HIV-associated sensory neuropathy (HIV-SN) is a nerve condition that causes pain, numbness, or tingling in the extremities. It can be caused both by the virus itself and by some HIV treatments, particularly the nucleoside reverse transcriptase inhibitors didanosine (Videx) and stavudine (Zerit).

The condition affects about 40 percent of all HIV patients on antiretroviral therapy and may become more common as more HIV-positive individuals begin antiretroviral treatment.

Currently, there are a variety of treatments prescribed to treat HIV-SN, but information on their efficacy for HIV-SN is limited because many of the drugs were designed to treat other conditions. For example, Lyrica (pregabalin) is approved to treat seizures, and amitriptyline is an antidepressant.

In their review, researchers sought to evaluate the effectiveness of these two drugs, as well as other commonly-used pain relievers, in treating HIV-SN. The review was based on 14 randomized, controlled clinical trials that investigated HIV-SN treatments.

Results showed that the only treatments to demonstrate greater efficacy than a placebo were smoked marijuana, high-dose topical capsaicin, and nerve growth factor. Topical capsaicin is a medicated cream or lotion for relieving joint and muscle pain that contains the active ingredient from chili peppers. Nerve growth factor is a small protein important for the growth, maintenance, and survival of certain nerve cells.

In contrast, the pain relievers amitriptyline, gabapentin (Neurontin) (a drug originally developed for the treatment of epilepsy that is now widely used as a pain reliever), Lyrica, prosaptide, peptide T, acetyl-L-carnitine, mexilitine (Mexitil), and low-dose topical capsaicin were no more effective in treating HIV-SN than placebos.

Lamotrigrine (Lamictal), another drug that was examined, may have been effective specifically in patients whose HIV-SN was linked to taking certain antiretrovirals known to cause the condition. For patients with HIV-SN in general, however, it was not more effective than a placebo.

Of the three drugs that demonstrated efficacy, only high-dose capsaicin is currently approved by the United States Food and Drug Administration (FDA). The FDA does not recommend smoked marijuana as therapy and nerve growth factor is not approved by the FDA.

The researchers did note that their results are somewhat limited by the lack of high-quality randomized, controlled trials investigating HIV-SN pain treatment. They added that their analysis was complicated by differing study designs and sizes.

The authors also pointed out that some of the trials included in the review did not take into account additional pain relievers being used by participants during the trials or whether participants had previously failed other pain relieving therapies. These conditions might have affected the results of the trials.

What's the point of comments...

...if they ignore the subject of the post and advertise something else?
I received the following 'comment' to the post about gene therapy. It may well be perfectly straightforward and helpful but it has nothing to do with gene therapy and is just advertising yet another 'pain clinic'. Come on guys! I've just posted about advertising via medical sites and then you get precisely that as the next comment! From now on, I will only publish comments which are relevant to the post itself (or a completely new subject that someone wants to talk about). If you're selling something, do it in your own space please.

Foreign Pharmacies said...
Florida Pain Clinics provide you with Pain relief medications and they have experts who are simply ideal and experienced with Pain Management skills.

In the Florida pain management clinics you will be provided with the bests of Pain relief medications and a variety many health care experts. They are trained and are experts in different pain management groups. Doctors in these clinics consist of rehabilitation doctors, anesthesiologists, neurologists, and probably every types of physician people need.

For the Pain relief medications there are different types of medicines that the Pain Management doctors utilize for bringing fast and permanent relief. Some of the commonly used Pain relief medications include Oxycodone, Hydrocodone, Acetaminophen, Lortab, Vicodin, Norco and many more. Let us discuss about each one of them and how they are helpful in controlling pain.

Gene Therapy Offers New Hope For Treatment Of Peripheral Neuropathy

ScienceDaily (June 1, 2007) (so not exactly new!)

— Researchers from the University of Pittsburgh School of Medicine report that they have successfully used gene therapy to block the pain response in an animal model of neuropathic pain, a type of chronic pain in people for which there are few effective treatments.



Neuropathic pain is the result of damage to nerve fibers caused by injuries or diseases, such as diabetes and cancer. These damaged nerve fibers continue to send signals to pain centers in the brain even after the surrounding tissue has healed. Unfortunately, neuropathic pain often responds poorly to standard pain treatments and occasionally may get worse instead of better over time. For some people, it leads to serious, long-term disability and dependence on pain medications that have a variety of unwanted side effects, including addiction.

The Pitt research team, led by Joseph Glorioso, III, Ph.D., chair of the department of biochemistry and molecular genetics, University of Pittsburgh School of Medicine, used a genetically engineered herpes simplex virus (HSV) to deliver the gene for part of the human glycine receptor (GlyR), a receptor found primarily on the surface of nerve cells in the spinal cord and the lower brain but not in the nerves in the limbs, to the paws of rats. A group of control rats received only the HSV vector without the inserted gene.

After the delivery of the therapeutic gene or empty vector (for the control group), the researchers injected the same paws of each rat with formalin, an irritant known to simulate the symptoms of a peripheral neuropathic pain at the site of injection. Following formalin injection, the rats were then given an injection of glycine to activate the GlyR receptor.

Both control and GlyR-HSV-infected rats showed a typical pain response to formalin. However, the application of glycine eliminated the pain response in GlyR-HSV infected animals, while it had no effect on animals infected with vector only. This alleviation of the pain response in GlyR-HSV-treated mice was reversed by the subsequent addition of low concentrations of strychnine, a strong GlyR-specific inhibitor, or antagonist.

According to Dr. Glorioso, these findings suggest that HSV-directed expression of GlyR in peripheral neurons and subsequent selective activation by glycine has the potential to be used therapeutically not only for neuropathic pain management but a variety of pain syndromes.

"The inability to effectively manage neuropathic pain associated with injuries and illnesses is a growing national and international problem. Gene therapy offers a more targeted, less toxic approach for effectively managing this condition. It also is our hope that targeted transgene delivery of GlyR may have even broader implications for managing a number of chronic pain syndromes, including pain resulting from shingles, arthritis and cancer," explained Dr. Glorioso.

These findings are being presented at the 10th annual meeting of the American Society of Gene Therapy, being held May 30 to June 3 at the Washington State Convention & Trade Center, Seattle.

In addition to Dr. Glorioso, others involved in the study included Michael Cascio, Ph.D., James Goss, Ph.D., David Krisky, M.D., Ph.D., and Rahul Scrinivasin, M.D., Ph.D., all with the department of molecular genetics and biochemistry, University of Pittsburgh School of Medicine.

Don't believe all you read!

Don't you just get tired of clicking on links hoping for information to help your condition and finding that most of them are linked to commercial products, books or services? I don't mind the ones with the flashing lights, Vegas dancers and lurid fonts...at least you can click straight away in disgust but the ones that really get under my skin are the ones which pretend to be kosher. Usually looking like real medical, or research websites, backed up by doctors and specialists and going into great detail about the condition when in fact all they want to do is lighten the weight of your wallet by selling you something!
Just be careful is all I'm saying, some of these sites are really clever in getting you to 'sign up'. This sort of spam is even more insidious than normal because it takes advantage of people who are looking for help.

Cannabis probably helps but...

I know exactly what he means!

A video from a blog entitled,Diabetic Neuropathy whats it all about hey! from a guy named Clayton. (Be patient, he's not the fastest speaker in the world but there will be many who can totally identify with what he says)

Can Cannabis help?

In the States, there are constant arguments regarding the value of cannabis in treating pain and most states have legal problems anyway. Here in the Netherlands, we have no such problems, so this should be of interest. The problem is that if you're a non-smoker, you might have extra difficulty using cannabis.
According to the Californian doctor, Dr. Sean Brean...

This week I was contacted by the director of operations for The Foundation for Peripheral Neuropathy in Chicago because of the feedback they are getting from patients about how much it helps them. Unfortunately Illinois does not have a medical marijuana law on the books so the patients there are frustrated and want relief. The women I spoke with reached out to me because I have blogged about the success I have had using medical marijuana to treat neuropathic pain. READ ON….
...Neuropathic pain can happen from a number of different reasons. One of the most common is cause by high circulating blood sugars seen in patients with Diabetes. These sugars bind to the nerves and alter various proteins resulting a damage. Also, diabetes affects the small blood vessels that supply the nerves. When the blood flow is limited there is less oxygen to the nerves and they die off. The #2 and #3 reasons patients develop neuropathy is HIV infection and medication induced (many chemotherapy agents cause neuropathy).

There have been numerous studies that show medical marijuana’s efficacy. If you google “Center for Medical Cannabis Research, UCSD” it will link to 14 completed studies showing the efficacy of medical marijuana. Many of those studies demonstrated the positive benefit of using marijuana for neuropathic pain.

When patients follow up with me after using medical marijuana they report:

1. Decreased dependance on other pain meds.

2. Improved sleep. Many times they sleep through the night “for the first time in years”.

3. Improved Mood. They now have hope and have a better outlook on their lives. Finally something that gave them some relief!

4. Improved appetite.

It has been very rewarding taking care of patients with neuropathic pain. Traditional medicine has not given enough credit to cannabis as a treatment for this disease. As more and more patients use this my hope is that more doctors will hear their success stories.
Medical Marijuana and Peripheral Neuropathy

From AidsMeds.com: the picture is becoming clearer for certain categories of HIV patients.

Peripheral Nerve Damage Remains Common Despite HIV Therapy



The prevalence of a sometimes-painful nerve condition called peripheral neuropathy (PN) remains high in people with HIV despite effective antiretroviral (ARV) therapy, according to a study published in the April 24 issue of AIDS. Older age, diabetes, a low CD4 count and the use of nerve-toxic ARV drugs were the strongest predictors of developing the condition.

Earlier in the epidemic, the three most common neurological conditions in people with HIV were the development of HIV-associated dementia (HAD), infection-related neurological diseases and PN. Since the introduction of effective combination ARVs in the late 1990s, however, the rates of HAD and infection-related diseases have fallen dramatically—leaving a continued high level of PN in people with the virus.

Peripheral neuropathy occurs when the long and short nerve fibers running from the brain to the hands and feet become damaged. Some people with PN don’t have noticeable symptoms, and the only way to diagnose the disease is for a provider to test whether they have a loss of sensation in their big toes or reduced reflexes in the ankles. Others, however, can have persistent tingling sensations or sharp shooting or throbbing pain in their feet and legs.

In the early to middle years of the epidemic, the factors most commonly associated with PN were low CD4s, high viral loads, diabetes and the use of either protease inhibitors (which can reduce the body’s ability to control blood sugar) or nucleoside reverse transcriptase inhibitors (NRTIs) that damage nerve cells—most notably Zerit (stavudine) and Retrovir (zidovudine).

To determine the prevalence of PN in the modern ARV era, and the factors associated with it, Scott Evans, PhD, from the Harvard School of Public Health in Boston, and his colleagues followed 2,141 HIV-positive people between 2000 and 2007 who started ARV therapy for the first time in six different studies sponsored by the AIDS Clinical Trials Group (ACTG).

People were tested for peripheral neuropathy every 48 weeks during the seven years of the study. Eighty-one percent of the participants were men, 32 percent were black, and the average age was 39. Before starting ARV therapy, 21 percent had PN, though most—80 percent—did not have symptoms.

Evans and his colleagues found that PN not only persisted but also continued to be diagnosed, despite the fact that 82 percent of the participants got and kept their HIV levels under control after starting ARVs. Over the course of seven years, the majority who were initially diagnosed with PN had persistence of the disease, and an additional 20 percent developed neuropathy, though the vast majority continued to be without symptoms.

Evans’s team found that the factors most strongly associated with developing PN were older age, diabetes, the use of nerve-toxic NRTIs and having a CD4 count less than 200. Other factors associated with developing PN included taller height, the use of protease inhibitors and the use of statin drugs, though these associations were much weaker.

For those who developed PN while on nerve-toxic NRTIs, just over half continued to have PN and 36 percent continued to have symptomatic PN after the drugs were withdrawn. The only factor associated with recovery from PN was younger age.

Overall, the authors conclude that providers should take particular care to prevent neuropathy or to intervene, when possible, quickly when symptoms develop. Most important, they say, is to develop alternatives to nerve-toxic NRTIs in the developing world, and to watch closely for neuropathy in older people with HIV, people who start ARV therapy late or who have persistently low CD4 counts and in people who have diabetes or nutritional deficiencies.

Neuropathy humour

Not much of it around actually - not high on the subject lists for open nights at the comedy clubs but I came across this (you know...via via)and even if you find it cringe making - give the guy a break...at least he's trying! Positive thinking...dontcha love it!

I've Got Neuropathy
(Sung to the tune of "Making Whoopee")
By: Roy C. Bennett

It's one p.m.
I'm at the doc's;
I've taken off
My shoes and socks.
He sticks a pin in;
I sit there grinnin' --
I've got neuropathy.

I'm on a date,
I'm getting bold;
Instead of hot,
I'm feeling cold.
My feet are freezin'
And here's the reason:
I've got neuropathy.

When there's a fire within me
Should I feel glad or sad?
Can this be love I'm feeling
Or just a nerve gone bad?

She wants to wed;
I'm all aglow.
Should I say yes?
Should I say no?
Oh, how I tingle,
But I'll stay single --
It's just....neuropathy.

Don't some of the so-called life-enhancing, self-help mottos and messages just make you want to spit!
This is a nice one for neuropathy patients...

"Life isn't about waiting for the storm to pass...
It's about learning to dance in the rain."

...feeling better yet?

Circle of Care - It's not always just about the patient!

From the site: http://www.neuropathy.org/
(a valuable site to add to your neuropathy Favourites list)

Angela Macropoulos — recently submitted a video for the 2011 Neuro Film Festival hosted by the American Academy of Neurology (AAN). We appreciate all those who voted for the film to be screened at the festival held during the AAN's annual meeting in April. We look forward to keeping you posted on how the film does.

A huge amount of work and information has gone into this book and it's full of useful tips - definitely worth the effort but tailored more towards the US and diabetic market.

Via Google reader: I could read it all in PDF format

You Can Cope with Peripheral Neuropathy
By: Mims Cushing, Norman Latov, M.D.Publisher: Demos Medical Publishing
Published on: 03/14/2005
Print ISBN: 9781932603767
Imprint: Demos Health
PreviewAvailable Formats: PDF

Peripheral neuropathy is one of the most common diseases most people never heard of…and yet, upwards of 20 million Americans have it! It is estimated that 60 to 70 percent of people with diabetes have mild to severe neuropathy. That fact alone is staggering. Other causes include vitamin deficiencies, autoimmune diseases, kidney, liver or thyroid disorders, cancer and a variety of other medical conditions.According to the Neuropathy Association the "extent and importance" of peripheral neuropathy has not yet been adequately recognized. The disease is apt to be misdiagnosed, or thought to be merely a side effect of another disease. However, people from all walks of life live with this neurological illness that has been described by those who have it as a tingling or burning sensation in their limbs, pins and needles and numbness.You Can Cope with Peripheral Neuropathy:365 Tips for Living a Full Life was written by both a patient-expert and doctor and is a welcome addition to the information on this subject. It covers such diverse topics as What to ask at doctor appointments Making the house easier to navigate with neuropathy Where to find a support group Using vitamins and herbs for treatment Tips for traveling And much, much more!You Can Cope With Peripheral Neuropathy is a compendium of tips, techniques, and life-task shortcuts that will help everyone who lives with this painful condition. It will also serve as a useful resource for their families, caregivers, and health care providers.

Venoms For Neuropathic Pain

Today's post is from sciencedaily.com (see link below) and talks about the pain killing properties of certain venoms. This seems to be a recurring theme - the same has been said of Black Widow Spider and certain snake venoms but hey, if it works!

Pinch Away the Pain: Scorpion Venom Could Be an Alternative to Morphine
ScienceDaily (Feb. 21, 2010)

Scorpion venom is notoriously poisonous -- but it might be used as an alternative to dangerous and addictive painkillers like morphine, a Tel Aviv University researcher claims.

Prof. Michael Gurevitz of Tel Aviv University's Department of Plant Sciences is investigating new ways for developing a novel painkiller based on natural compounds found in the venom of scorpions. These compounds have gone through millions of years of evolution and some show high efficacy and specificity for certain components of the body with no side effects, he says.

Peptide toxins found in scorpion venom interact with sodium channels in nervous and muscular systems -- and some of these sodium channels communicate pain, says Prof. Gurevitz. "The mammalian body has nine different sodium channels of which only a certain subtype delivers pain to our brain. We are trying to understand how toxins in the venom interact with sodium channels at the molecular level and particularly how some of the toxins differentiate among channel subtypes.

"If we figure this out, we may be able to slightly modify such toxins, making them more potent and specific for certain pain mediating sodium channels," Prof. Gurevitz continues. With this information, engineering of chemical derivatives that mimic the scorpion toxins would provide novel pain killers of high specificity that have no side effects.

An ancient Chinese secret?

In his research, Prof. Gurevitz is concentrating on the Israeli yellow scorpion, one of the most potent scorpions in the world. Its venom contains more than 300 peptides of which only a minor fraction has been explored. The reason for working with this venom, he says, is the large arsenal of active components such as the toxins that have diversified during hundreds of millions of years under selective pressure. During that process, some toxins have evolved with the capability to directly affect mammalian sodium channel subtypes whereas others recognize and affect sodium channels of invertebrates such as insects. This deviation in specificity is for us a lesson of how toxins may be manipulated at will by genetic engineering, he says.

While the use of scorpion venom to treat some body disorders seems counter-intuitive, the Chinese have recognized its effectiveness hundreds of years ago. "The Chinese, major practitioners of what we call 'alternative medicine,' use scorpion venom, believing it to have powerful analgesic properties," Prof. Gurevitz says. Some studies have also shown that scorpion venom can be used to treat epilepsy. "We study how these toxins pursue their effects in the Western sense to see how it could be applied as a potent painkiller."

Using an approach called "rational design" or "biomimicry," Prof. Gurevitz is trying to develop painkillers that mimic the venom's bioactive components. The idea is to use nature as the model, and to modify elements of the venom so that a future painkiller designed according to these toxins could be as effective as possible, while eliminating or reducing side effects.

No more morphine addicts

Finding a new and effective pain medication could solve one of the biggest problems in the medical world today. Pain is an important physiological response to danger, physical injury and poor health, yet doctors need to reduce extreme pain in patients which aspirin could never palliate. To date, opiate-derived painkillers have been quite effective, but the medical community is eager to find other solutions due to the risks associated with their use.

"This new class of drugs could be useful against serious burns and cuts, as well as in the military and in the aftermath of earthquakes and natural disasters. Instead of running the risk of addiction, this venom-derived drug, mimicking the small peptide toxin, would do what it needs to do and then pass from the body with no traces or side-effects," Prof. Gurevitz says.

http://www.sciencedaily.com/releases/2010/02/100216163341.htm

Bring it on! We need to interrupt the morphine spiral!

Powerful New Painkiller With No Apparent Side Effects or Addictive Qualities, May Be Ready in a Year
ScienceDaily (Jan. 30, 2011) — A powerful new painkiller, which was developed on the basis of the research conducted at Stony Brook University and with no apparent side effects or addictive qualities, may now be only a year or two from the consumer market.


--------------------------------------------------------
"This offers a major paradigm shift in the control of pain," declares Dr. Simon Halegoua, Professor of Neurobiology & Behavior at Stony Brook who in the 1990s, teamed up with fellow Stony Brook professors Dr. Gail Mandel and Dr. Paul Brehm to identify a novel sodium ion channel involved in the transmission of pain. They predicted that a drug aimed at blocking this channel, PN1/Nav 1.7, would control pain. PN1 (Peripheral Neuron 1), is uniquely expressed in peripheral nerves such as those involved in pain transduction.

"When a patient is given an opiate like morphine, pain signals are still transmitted from sensory nerves to the central nervous system. Morphine action throughout the brain reduces and alters pain perception, but it also impairs judgement and results in drug dependence," explains Halegoua, also director of the Center for Nervous System Disorders at Stony Brook University. "With drugs targeting the PN1/Nav1.7 sodium ion channel, the pain signals would not be transmitted, even by the sensory nerves. And since the central nervous system is taken out of the equation, there would be no side effects and no addictive qualities."

The potential for such drugs is enormous -- the reduction or elimination of pain for patients with cancer, arthritis, migraine headaches, muscle pain, pain from burns, and pain from other debilitating diseases.

He notes that drugs in both oral and topical ointment forms, based on the research he conducted in a basement laboratory at Stony Brook with Mandel, a molecular biologist, and Brehm, an electrophysiologist, are currently in Phase II clinical trials in England and Canada.

The Research Foundation of the State University of New York is the holder of the various patents originating from the work of the Stony Brook researchers. Icagen Inc., now in partnership with Pfizer, holds the exclusive license to these patents and has announced their own drug has now entered Phase I clinical trials in the U.S.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Stony Brook University.