An Opioid Without Side Effects For Nerve Pain Is That Possible

Today's post is from genengnews.com (see link below). Don't you just love reading an article that contains a sentence like: “Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide–binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3′,5′-monophosphate inhibition in vitro.”!! However, with this sort of text, you have to remember that the ordinary neuropathy patient is essentially not the target audience here and this sort of article needs to be read with a sort of 'skim' technique that gives you the gist of what's being said, while skipping over the techno-speak. The article talks about a new form of opioid that is being developed that does the pain-killing job very effectively but doesn't have the side-effects that the media and politicians just can't cope with at the moment. We have to applaud research in the opioid field that doesn't begin with a skull and crossbones declaration that 'all opioids are bad'. Here they are genuinely recognising the benefits of opioids while trying to eliminate the potential harmful side effects. The whole world seems to be searching for opioid alternatives at the moment (powerful lobby - the anti-opioidals!) when the logical thing to search for is opioid adaptations that make them more user-friendly. Worth a read - you'll get the message I promise you.

Opioid Acts Only on Hurt Tissues, Skips Side Effects 
March 6, 2017 Gen News Highlights

  A new opioid can target “disease-specific” (pathological rather than physiological) conformations of receptors and ligands by selectively activating opioid receptors where acidic conditions prevail, as in tissues affected by inflammation or injury. Thus, the opioid brings pain relief at the site of inflammation and does not affect healthy tissues, such as those of the brain or intestinal wall, thereby avoiding side effects. [G. Del Vecchio & V. Spahn/Freepik]

Opioids, like sledgehammers, are powerful but blunt tools. When they are used to flatten pain, opioids may give other things a pounding, too. The problem is conventional opioids act on inflamed or damaged tissues as well as healthy tissues. Consequently, while opioids may relieve pain, they may also cause serious side effects, such as drowsiness, nausea, constipation, and dependency—and in some cases, respiratory arrest.

In hopes of finding a way to craft finer painkilling tools, scientists based at Charité-Universitätsmedizin Berlin scrutinized different ways opioids can interact with opioid receptors. These scientists, led by Prof. Dr. Christoph Stein, were on the lookout for “disease-specific” opioid receptor-ligand conformations. That is, the scientists plan was to exploit pathological (rather than physiological) conformation dynamics in the design of new opioids, and thereby create drugs that would target damaged or inflamed tissues yet bypass healthy tissues.

"By analyzing drug–opioid receptor interactions in damaged tissues, as opposed to healthy tissues, we were hoping to provide useful information for the design of new painkillers without harmful side effects," said Prof. Dr. Stein.

Prof. Dr. Stein’s team was aware that previous strategies in drug development had focused on central opioid receptors in noninjured environments, even though many painful syndromes (such as arthritis, neuropathy, and surgery) are driven by peripheral sensory neurons and are typically accompanied by inflammation with tissue acidosis. Ultimately, the team decided that this alternative mechanism of action—the binding and activation of peripheral opioid receptors—could be preferentially exploited by a new class of opioids. The key was the occurrence of acid conditions.

By following through on this idea, the scientists designed a new opioid that, unlike clinically used opioids, best activates the receptors in acidified tissues. When the new opioid was evaluated in a rat model of inflammatory pain, it exerted strong pain relief essentially without the side effects of standard opioids.

Details appeared March 3 in the journal Science, in an article entitled, “A Nontoxic Pain Killer Designed by Modeling of Pathological Receptor Conformations.” The article describes how the scientists used computer modeling to analyze morphine-like molecules and their interactions with opioid receptors. In particular, computer modeling was used to simulate an increased concentration of protons, thereby mimicking the acidic conditions found in inflamed tissues.

“By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, because of its low acid dissociation constant, selectively activates peripheral μ-opioid receptors at the source of pain generation,” wrote the article’s authors. “Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide–binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3′,5′-monophosphate inhibition in vitro.”

The authors observed that their novel opioid produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting respiratory depression, sedation, constipation, or addiction potential. These results, the authors suggested, mean that treating postoperative and chronic inflammatory pain should now be possible without causing side effects. Doing so would substantially improve patient quality of life.

“In contrast to conventional opioids, our NFEPP-prototype appears to only bind to, and activate, opioid receptors in an acidic environment,” explained the study's first authors, Dr. Viola Spahn and Dr. Giovanna Del Vecchio. “This means it produces pain relief only in injured tissues, and without causing respiratory depression, drowsiness, the risk of dependency, or constipation."

"We were able to show that the protonation of drugs is a key requirement for the activation of opioid receptors," the authors concluded. Their findings, which may also apply to other types of pain, may even find application in other areas of receptor research. Thereby, the benefits of improved drug efficacy and tolerability are not limited to painkillers, but may include other drugs as well.

http://www.genengnews.com/gen-news-highlights/opioid-acts-only-on-hurt-tissues-skips-side-effects/81253978

Lyrica Pregabalin Side Effects

Today's post from peoplespharmacy.com (see link below) adds to the ever-growing discussion about Lyrica (pregabalin) as a treatment for nerve pain. It may be worth stating here that in May 2012, the makers Pfizer, withdrew their positive advice for Lyrica, with regard to people with HIV-related or diabetes-related neuropathy. Many doctors across the world have chosen to ignore the hint and continue to prescribe the drug widely for both sorts of neuropathy patient. Like all other treatments for nerve pain it's a drug that can have significant side effects, so it's always worth discussing seriously with your doctor whether it's appropriate for you. Opinions seem to be divided but if Pfizer themselves will not promote their own best-seller for two types of neuropathy, it's certainly worth questioning if it's the right treatment for you. Other articles on Lyrica can be found by looking at the alphabetical list on the right of this blog.

Lyrica Side Effects and Withdrawal are Worrisome
August 1, 2013 in People's Pharmacy Alerts

Have you been seeing the ad blitz for Lyrica (pregabalin)? A LOT of money is being spent trying to convince the American public that Lyrica is the answer to diabetic nerve pain. One of the most compelling commercials stars a retired policeman:

"Hi, I'm terry and I have diabetic nerve pain. I worked a patrol unit for 17 years in the city of Baltimore. When I first started experiencing the pain it's hard to describe because you have a numbness but yet you have the pain like thousands of needles sticking in your foot."

Sounds awful and indeed people with diabetic neuropathy suffer terribly. Symptoms can include:

SYMPTOMS OF DIABETIC NEUROPATHY
Burning, tingling or a feeling of needles sticking into your skin
Numbness in toes and feet; an inability to sense a needle prick; reduced sensitivity to temperature change
Difficulty walking either because of numbness, pain or weakness
Intense stabbing jolts of pain, especially in the evening
Other complications of nerve damage include sexual dysfunction, swallowing difficulties, poor stomach emptying leading to feelings of fullness and bloating, bladder problems and dizziness on standing.

It's hardly any wonder that patients with neuropathy and nerve pain would be looking for help. A commercial like the one with Terry, the retired Baltimore police officer, is very appealing. When Terry says the "pain started subsiding" after taking Lyrica, we imagine that lots of viewers might think that they too might benefit from this drug. Are they paying attention, though, when the voice-over announcer says:

"Lyrica is not for everyone. It may cause serious allergic reactions or suicidal thoughts or actions. Tell your doctor right away if you have these: new or worsening depression or unusual changes in mood or behavior, or swelling, trouble breathing, rash, hives, blisters, changes in eye sight including blurry vision, muscle pain with fever, tired feeling or skin sores from diabetes. Common side effects are dizziness, sleepiness, weight gain, and swelling of hands, legs and feet. Don't drink alcohol while taking Lyrica. Don't drive or use machinery until you know how Lyrica affects you."

While you listen to the on-air announcer speed through this long list of complications you see Terry working in his backyard planting and watering pretty flowers. Somehow, the scary side effects seem less worrisome in such a bucolic setting.

Here are some real stories from our website to bring the side effects into focus:

This comes from LCB:

"I started taking Lyrica 10 days ago for RLS [restless leg syndrome] and fibromyalgia. I was taking gabapentin but it had stopped working. I gained 14 pounds on the gabapentin, and now I've gained 5 pounds more on the Lyrica. I have edema [fluid retention] as well. I'm sleepy for most of the day and I feel like I'm dragging my body around. I have no energy. My husband tells me I'm irritable with the kids, and that I can't seem to remember things anymore.

"All of this is quite a drastic change from my usual energetic, tireless self. I don't like how I feel, and to make the most important point: Lyrica doesn't seem to help much. I still have tons of pain, and RLS at night. So, I have an appointment with my doctor to ask for a change. I believe that these medicines work very well on some people, but we are all so different. It doesn't work for me."

T. had a very scary story to share:

"After almost eight years on Cymbalta, it had lost the effectiveness. My doctor added Lyrica to help with fibro. Soon after, I started to have a deep depression and wanted to end the pain that I have lived with for so long. The stress of life was so great, that I attempted suicide. I was put in the hospital for four days.

"At that point, no more meds! The symptoms are what everyone has described. I feel alone and lost in my own brain fog hell. Not one of my family has a clue what a nightmare this is."

Kathy listed these complicatons:

"I was on the drug eight months for fibromyalgia prescribed by a rheumatologist. I, too, started having problems with eyesight (my eye doctor could NOT update my lenses due to Lyrica causing severe blurriness). I also had memory loss, anxiety, and trouble sleeping. I suffer from chronic constipation due to diverticulitis, and the Lyrica was making this worse. I weaned off over a three-week period. OMG! The withdrawal was/is terrible.

"I am 9 weeks into it, and still have terrible throbbing ongoing headaches, difficulty swallowing, and went from 134 lbs to 118! I feel like I'm dying most of the time. I went to my current neurologist today and was told there were no such symptoms from Lyrica withdrawal!

"Google it, doctor! Please, if anyone reading this is considering taking Lyrica, reconsider! If you have side effects like I did, then decide to go off; you may be looking at a long recovery and NO help from a doctor. They are all denying any problems with this medication. Please read the "Lyrica Withdrawal" posts first!"

Getting off drugs that affect the central nervous system can sometimes be challenging. As we mentioned recently with our post on Abilify, the track record of psychiatry and neurology has been abysmal when it comes to studying sudden withdrawal from commonly prescribed medications. It took years for researchers to discover that when patients suddenly stopped benzodiazepines such as alprazolam (Xanax), diazepam (Valium) or lorazepam (Ativan) they often experienced very unpleasant withdrawal symptoms. Ditto for antidepressants like citalopram (Celexa), duloxetine (Cymbalta), escitalopram (Lexapro), sertraline (Zoloft) and venlafaxine (Effexor).

The story of Lyrica (pregabalin) withdrawal is also murky. There is very little in the medical literature on this topic. The prescribing information does mention, though, that some patients report symptoms such as insomnia, nausea, headache, anxiety, sweating or diarrhea if they stop suddenly. The advice: taper the dose over at least a week rather that stopping suddenly. We fear that such information is not always that helpful, especially since there is not much practical information about actual dosage reduction.


LYRICA SIDE EFFECTS:

Vertigo, dizziness, unsteadiness, coordination problems, abnormal gait
Sleepiness, fatigue
Confusion, abnormal thinking, difficulty with attention and concentration, accidental injury
Dry mouth
Fluid retention in hands or feet, edema
Blurred vision, difficulty with eyesight
Weight gain,
Constipation, gas
Pain
Skin reaction, rash, dermatitis (requires immediate medical attention!)
Depression, suicidal thoughts or actions
Muscle breakdown (rhabdomyolysis), tremor
Blood disorders
Withdrawal symptoms, discontinuation syndrome, seizures

We recognize that some people with hard-to-treat neuropathy or fibromyalgia may do quite well on Lyrica and not suffer side effects. That's great. But some patients don't get much benefit and do suffer complications. For them, Lyrica is not a blessing.

To learn about some other approaches to neuropathy, you may want to check these links about benfotiamine and alpha lipoic acid.

Please share your own story about Lyrica, neuropathy and what has worked or caused problems for you below in the comment section so others can benefit from your experience.

http://www.peoplespharmacy.com/2013/08/01/post-11/

Neuropathy As A Side Effect Of Lyme Disease

Today's post from lymeneteurope.org (see link below) is possibly not for every reader as it talks about neuropathy caused by Lyme Disease. It's a very long (hence the smaller than normal typeface) and technical post, consisting of complex abstracts from many studies but if you have Lyme disease and/or neuropathy caused by Lyme disease, then there is a vast amount of useful information for you to digest here. Tics that cause Lyme disease are spreading rapidly in many parts of the world and you may not be aware that you have been bitten at all. If you're not already aware of the general facts about how this condition is caused, there are other shorter and simpler articles here on the blog (use the search button to the right) or you may want to Google Lyme disease itself. I am very grateful to Rita A for collecting all this information in one place - it will help a lot of people to understand the connection between Lyme disease and neuropathy.

Older Articles re LD and Neuropathy
by RitaA Sun 22 Jan 2012
I was reading about Lyme disease and peripheral neuropathy earlier, and did a bit of digging for published articles about the topic. Neuropathy does seem to be a common finding in both early and late Lyme disease. I've also included a couple of articles dealing with Lyme disease from a neuropsychiatric point of view:

Neurology. 1987 Nov;37(11):1700-6.
Lyme disease: cause of a treatable peripheral neuropathy.
Halperin JJ, Little BW, Coyle PK, Dattwyler RJ.
Source
Department of Neurology, State University of New York, Stony Brook 11794.
Abstract
Peripheral nerve dysfunction was demonstrated in 36% of patients with late Lyme disease. Of 36 patients evaluated, 14 had prominent limb paresthesias. Thirteen of these had neurophysiologic evidence of peripheral neuropathy; neurologic examinations were normal in most. Repeat testing following treatment documented rapid improvement in 11 of 12. We conclude that this neuropathy, which is quite different from the infrequent peripheral nerve syndromes previously described in this illness, is commonly present in late Lyme disease. This neuropathy presents with intermittent paresthesias without significant deficits on clinical examination and is reversible with appropriate antibiotic treatment. Neurophysiologic testing provides a useful diagnostic tool and an important measure of response to treatment.

PMID: 3670609 [PubMed - indexed for MEDLINE]

Neurology. 1989 Jun;39(6):753-9.
Lyme neuroborreliosis: central nervous system manifestations.
Halperin JJ, Luft BJ, Anand AK, Roque CT, Alvarez O, Volkman DJ, Dattwyler RJ.
SourceDepartment of Neurology, State University of New York, Stony Brook.
Abstract
We evaluated 85 patients with serologic evidence of Borrelia burgdorferi infection. Manifestations included encephalopathy (41), neuropathy (27), meningitis (2), multiple sclerosis (MS) (6), and psychiatric disorders (3). We performed lumbar punctures in 53, brain MRI in 33, and evoked potentials (EPs) in 33. Only patients with an MS-like illness had abnormal EPs, elevated IgG index, and oligoclonal bands in the cerebrospinal fluid. Twelve of 18 patients with encephalopathy, meningitis, or focal CNS disease had evidence of intrathecal synthesis of anti-B burgdorferi antibody, compared with no patients with either MS-like or psychiatric illnesses, and only 2/24 patients with neuropathy. MRIs were abnormal in 7/17 patients with encephalopathy, 5/6 patients with an MS-like illness, and no others. We conclude that (1) intrathecal concentration of specific antibody is a useful marker of CNS B burgdorferi infection; (2) Lyme disease causes an encephalopathy, probably due to infection of the CNS; (3) MS patients with serum immunoreactivity against B burgdorferi lack evidence of CNS infection with this organism.

Comment in
Neurology. 1990 Jan;40(1):189-91.
Neurology. 1991 Jun;41(6):952-3.

PMID:2542840[PubMed - indexed for MEDLINE]

Rev Infect Dis. 1989 Sep-Oct;11 Suppl 6:S1499-504.
Abnormalities of the nervous system in Lyme disease: response to antimicrobial therapy.Halperin JJ.
Source
Department of Neurology, State University of New York, School of Medicine, Stony Brook 11794.
Erratum in
Rev Infect Dis 1990 May-Jun;12(3):566.
Abstract
Objective measures of neurologic function were used to assess response to treatment in patients with late Lyme borreliosis. Neurophysiologic evidence of peripheral neuropathy was present in 64 of 137 patients tested. Measures of distal axon function (sensory amplitude and conduction velocity, motor terminal latency) were most affected.Repeat studies following 60 patients receiving antimicrobial therapy demonstrated significant improvement in these values. Before and after therapy 17 patients with late Lyme borreliosis and prominent subjective cognitive dysfunction underwent neuropsychologic tests of memory, conceptual ability, concentration, psychomotor function, overlearned intellectual abilities, and mood. Significant abnormalities were evident before treatment; all reversed with antimicrobial therapy. Many patients with this encephalopathy had specific abnormalities revealed by magnetic resonance imaging of the brain and had evidence of intrathecal synthesis of antibody to Borrelia. These findings indicate that late Lyme borreliosis commonly causes nervous system abnormalities that are reversible with appropriate antibiotic therapy.

PMID: 2682962 [PubMed - indexed for MEDLINE]

Brain. 1990 Aug;113 ( Pt 4):1207-21.
Lyme neuroborreliosis. Peripheral nervous system manifestations.
Halperin J, Luft BJ, Volkman DJ, Dattwyler RJ.
SourceDepartment of Neurology, State University of New York, Stony Brook 11794.
Abstract
An ever increasing number of apparently unrelated peripheral nervous system (PNS) disorders has been associated with Lyme borreliosis. To ascertain their relative frequency and significance, we studied prospectively 74 consecutive patients with late Lyme disease, with and without PNS symptoms: 53% had intermittent limb paraesthesiae, 25% the carpal tunnel syndrome, 8% painful radiculopathy, and 3% Bell's palsy; 39% had disseminated neurophysiological abnormalities. To assess the interrelationships among these syndromes, we reviewed the neurophysiological findings in all 163 such patients that we have studied to date. Reversible abnormalities of distal conduction were the most common finding. Demyelinating neuropathy was extremely rare. The pattern of abnormality was similar in all patient groups, regardless of whether the symptoms suggested radiculopathy, Bell's palsy, or neuropathy. We conclude that (1) reversible PNS abnormalities occur in one-third of our patients with late Lyme borreliosis, and (2) the pattern of electrophysiological abnormalities is the same in all and is indicative of widespread axonal damage, suggesting that these different presentations reflect varying manifestations of the same pathological process.
PMID:2168778[PubMed - indexed for MEDLINE]

N Engl J Med. 1990 Nov 22;323(21):1438-44.
Chronic neurologic manifestations of Lyme disease.
Logigian EL, Kaplan RF, Steere AC.
SourceDepartment of Neurology, Tufts University School of Medicine, Boston, MA 02111.
Abstract
BACKGROUND AND METHODS: Lyme disease, caused by the tick-borne spirochete Borrelia burgdorferi, is associated with a wide variety of neurologic manifestations. To define further the chronic neurologic abnormalities of Lyme disease, we studied 27 patients (age range, 25 to 72 years) with previous signs of Lyme disease, current evidence of immunity to B. burgdorferi, and chronic neurologic symptoms with no other identifiable cause. Eight of the patients had been followed prospectively for 8 to 12 years after the onset of infection.

RESULTS: Of the 27 patients, 24 (89 percent) had a mild encephalopathy that began 1 month to 14 years after the onset of the disease and was characterized by memory loss, mood changes, or sleep disturbance. Of the 24 patients, 14 had memory impairment on neuropsychological tests, and 18 had increased cerebrospinal fluid protein levels, evidence of intrathecal production of antibody to B. burgdorferi, or both. Nineteen of the 27 patients (70 percent) had polyneuropathy with radicular pain or distal paresthesias; all but two of these patients also had encephalopathy. In 16 patients electrophysiologic testing showed an axonal polyneuropathy. One patient had leukoencephalitis with asymmetric spastic diplegia, periventricular white-matter lesions, and intrathecal production of antibody to B. burgdorferi. Among the 27 patients, associated symptoms included fatigue (74 percent), headache (48 percent), arthritis (37 percent), and hearing loss (15 percent). At the time of examination, chronic neurologic abnormalities had been present from 3 months to 14 years, usually with little progression. Six months after a two-week course of intravenous ceftriaxone (2 g daily), 17 patients (63 percent) had improvement, 6 (22 percent) had improvement but then relapsed, and 4 (15 percent) had no change in their condition.

CONCLUSIONS: Months to years after the initial infection with B. burgdorferi, patients with Lyme disease may have chronic encephalopathy, polyneuropathy, or less commonly, leukoencephalitis. These chronic neurologic abnormalities usually improve with antibiotic therapy.

Comment in
N Engl J Med. 1991 Apr 18;324(16):1137.
PMID:2172819[PubMed - indexed for MEDLINE] Free full text

Scand J Infect Dis Suppl. 1991;77:74-80.
North American Lyme neuroborreliosis.
Halperin JJ.
SourceDepartment of Neurology, State University of New York, Stony Brook 11794.
Abstract
Clinical, neurophysiologic and laboratory findings obtained in American patients with nervous system Lyme borreliosis were compared to published observations in European neuroborreliosis patients. In both populations, Borrelia burgdorferi infection is commonly associated with neurologic abnormalities. European reports have emphasized dramatic clinical phenomena, such as painful radiculitis (Garin-Bujadoux-Bannwarth syndrome) and chronic progressive spastic paraparesis. North American patients seem to develop milder forms of nervous system involvement. Peripheral nervous system manifestations take a variety of forms, ranging from mild, intermittent sensory symptoms, to typical painful radiculitis. Despite the range of clinical presentations, neurophysiologic and morphologic analyses indicate these all represent different manifestations of the same pathophysiologic process, which, in turn, is similar to what has been described in Garin-Bujadoux-Bannwarth syndrome. Similarly, central nervous system (CNS) symptoms vary widely, ranging from a mild confusional state to a severe encephalitis. The encephalitis is probably due to direct CNS infection. In some instances the confusional state may also be due to CNS infection but it is likely that in many patients it is not. As in European patients, the most reliable indicator of CNS infection appears to be the intrathecal production of anti-B burgdorferi antibodies. Although North American Lyme borreliosis patients may often develop milder forms of nervous system involvement that their European counterparts, there is considerable overlap, and the underlying pathophysiologic mechanisms are probably identical.

PMID:1658921[PubMed - indexed for MEDLINE]

Scand J Infect Dis Suppl. 1991;77:64-73.
Neurological manifestations of Lyme borreliosis: clinical definition and differential diagnosis.
Kristoferitsch W.
SourceDepartment of Neurology, Wilhelminen-Spital der Stadt Wien, Vienna, Austria.

Abstract
Neurological manifestations occur in early disseminated Lyme Borreliosis and in the chronic late stage. Two of them, Bannwarth's syndrome and acrodermatitis chronica atraphicans-associated neuropathy, were known as well defined clinical entities many years prior to the detection of their causative agent. Soon after B. burgdorferi was identified and serologic tests became available, many reports were published which attributed to a large variety of different neurological disorders to Lyme borreliosis. In many cases the diagnosis was primarily based on serodiagnostic results. Yet some scepticism is indicated since 10-30% of the population in endemic areas have been found to be seropositive. While prior to 1983 and before the availability of serodiagnostic tests neurological manifestations of Lyme borreliosis were recognized by a minority of neurologists, they now seem to be overdiagnosed. Therefore clear diagnostic criteria have to be set up. They include the clinical picture, other preceding or concomitant diseases of the Lyme borreliosis complex, serodiagnostic results, cerebrospinal fluid findings, demonstration of intrathecal specific antibody synthesis, results of nerve biopsies, response to adequate antibiotic therapy and exclusion of other diseases. The significance of each of these criteria depends on the clinical involvement and on the stage of Lyme borreliosis.

PMID:1947814[PubMed - indexed for MEDLINE]

Arch Neurol. 1991 Nov;48(11):1125-9.
Cognitive functioning in late Lyme borreliosis.
Krupp LB, Masur D, Schwartz J, Coyle PK, Langenbach LJ, Fernquist SK, Jandorf L, Halperin JJ.
SourceDepartment of Neurology, State University of New York, Stony Brook 11794.
Abstract
Lyme borreliosis, a tick-borne multisystem disease, may cause a variety of neurologic complications, including meningoencephalitis and encephalopathy. To evaluate neurobehavioral function following treated Lyme borreliosis, 15 patients with Lyme disease and complaints of persistent cognitive difficulty a mean of 6.7 months following antibiotic treatment underwent neuropsychological evaluation and were compared with 10 healthy controls, matched in aggregate for age and education, who underwent the identical neuropsychological assessment.Compared with controls, patients with Lyme disease exhibited marked impairment on memory tests and particularly on selective reminding measures of memory retrieval. The memory impairment did not correlate with serum or cerebrospinal fluid anti-Borrelia burgdorferi antibody titers and was not explained by magnetic resonance imaging findings or depression. The cause of this encephalopathy is currently unknown; however, indirect effects of systemic infection or other toxic-metabolic factors may be partly responsible.

Comment in
Arch Neurol. 1992 Oct;49(10):1011.
PMID:1953395[PubMed - indexed for MEDLINE]

Ital J Neurol Sci. 1992 Dec;13(9 Suppl 14):85-90.
Neurological complications of Lyme borreliosis.
Meier C.
SourceDepartment of Neurology, University of Berne, Switzerland.
Abstract
Lyme disease, like syphilis, a spirochetal infection, can appear with exacerbations and remissions in different stages. The clinical picture is marked by dermatological, neurological, rheumatic and cardiological complications.PNS complications appear in the second and third stage. Tick bite meningoradiculoneuritis neuritis (Garin-Bujadoux-Bannwarth-Syndrome), characterized by painful asymmetrical sensory and motor dysfunctions and inflamed CSF, is a typical manifestation of the second stage. Mononeuritis multiplex appearing in conjunction with acrodermatitis chronica atrophicans is a typical PNS manifestation of the third stage. CNS involvement may also occur in early and late stages of Lyme-Borreliosis, presenting as myelitis or progressive encephalomyelitis. Lyme-Borreliosis is a treatable condition, which should not be missed in the differential diagnosis of PNS and CNS disorders.PMID:1345745[PubMed - indexed for MEDLINE]

Am J Phys Med Rehabil. 1996 Jul-Aug;75(4):314-6.
Lyme borreliosis neuropathy. A case report.
Deltombe T, Hanson P, Boutsen Y, Laloux P, Clerin M.
Source
Department of Physical Medicine and Rehabilitation, University Hospital of Mont-Godinne UCL, Yvoir, Belgium.

Abstract
Lyme borreliosis is responsible for a large variety of peripheral neurologic manifestations including axonal polyneuropathy, radiculopathy, and facial nerve palsy. The prevalence of the disease must draw our attention on the possible responsibility of Borrelia burgdorferi in the pathogenesis of such symptomatology. Electrophysiologic studies demonstrate a proximal and distal axonal involvement, whereas neuropathologic studies suggest that vasculitis might be one of the primary pathophysiologic mechanisms. Electromyography provides a useful diagnostic tool and an important measure of response to treatment. Although peripheral neuropathy usually improves, our case report confirms the fact that chronic neurologic manifestations may not consistently resolve with appropriate treatment.

PMID:8777029[PubMed - indexed for MEDLINE]

Semin Neurol. 1997 Mar;17(1):25-30.
Peripheral nervous system Lyme borreliosis.
Logigian EL.
SourceHarvard Medical School, Clinical Neurophysiology Laboratory, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Abstract
There are acute and chronic Lyme neuropathies. The seasonal acute syndromes of cranial neuritis or radiculoneuritis are generally quite distinctive, but may cause diagnostic difficulty when one syndrome occurs without the other, when erythema migrans is absent or missed, and when meningeal signs are minimal or absent. The chronic Lyme radiculoneuropathies are less severe, and less distinctive. Their recognition depends on eliciting a history of earlier classical manifestations of Lyme disease and by laboratory testing. In both acute and chronic Lyme radiculoneuropathy, electrophysiologic testing often proves the presence of a sensorimotor, axon loss polyradiculoneuropathy. Both acute and chronic Lyme radiculoneuropathy have similar pathologic features and can be classified as a nonvasculitic mononeuritis multiplex. The pathogenesis is uncertain; both direct infection as well as parainfectious mechanisms may play a role. The treatment with which we have the most experience is intravenous ceftriaxone 2 g/day for 2 to 4 weeks. Improvement occurs rapidly over days to weeks in early Lyme neuroborreliosis, but slowly over many months in chronic neuroborreliosis.

PMID:9166956[PubMed - indexed for MEDLINE]

Here is one of the webpages that prompted my search for peer-reviewed, published articles:

http://peripheralneuropathycenter.uchic ... ease.shtml


Types of Peripheral Neuropathy – Inflammatory

Lyme Disease

Lyme disease is an inflammatory disease that rapidly progresses. Transmitted by the bite of an infected deer tick, Lyme disease is most common in the Northeast section of the United States. However, the disease has also appeared in the upper East coast, in the upper Midwest, and along the coasts of northern California and Oregon.

Signs of Lyme disease include skin rash and painful inflammation of joints (particularly the knees), accompanied by flu-like symptoms. The symptoms of Lyme disease increase in severity as the disease spreads though the body.

Early diagnosis and treatment are important to stop the progression of the disease. If untreated, the disease can result in neurological disorders such as peripheral neuropathy, including Bell's palsy, as well as pain, numbness or weakness in the limbs. The onset of peripheral neuropathy typically develops weeks, months or years later, if the disease is left untreated.

While potentially serious, Lyme disease can be treated, especially in the early stages. It is important to take preventive measures when outdoors in areas known to have infected deer ticks. Some helpful steps include: wearing enclosed shoes and light colored clothing; checking clothing and exposed skin frequently for ticks; and using insect repellant containing DEET (Diethyl-meta-toluamide) on skin or clothes.

SYMPTOMS

(Not all symptoms and signs may be present.)

Lyme disease progresses in three stages of severity:

First Stage:

Fatigue
Fever and chills
Muscle and joint pain
Red circular rash
Stiff neck
Swollen lymph nodes

Second Stage:

Facial paralysis (Bell's palsy)
Irregular heartbeat
Meningitis (fever, stiff neck, severe headaches)
Numbness and pain in arms and legs
Stiff neck
Poor coordination

Third Stage:

Chronic arthritis and swelling in large joints, especially the knees
Chronic pain in muscles
Problems with sleeping
Numbness and pain in arms and legs
Nervous system problems
Difficulty concentrating
Memory loss
Numbness and tingling
Peripheral neuropathy
Pain, numbness and tingling in limbs
Paralysis of facial muscles (Bell's palsy)

EVALUATION AND TESTS
(Not all evaluation and tests may be necessary.)

Neurological exam
Electromyography
Nerve conduction velocity test
Blood tests, including tests for antibody against the agent that causes Lyme disease and tests to detect the agent itself.

TREATMENT AND THERAPY
(Not all treatments and therapies may be indicated.)

Antibiotics
Intravenous therapy
[snip]

Lyme disease is curable, if treated early

And here is the other website that contains more detailed information about peripheral neuropathy in general, as well as what research is currently underway:

(I snipped out the parts having to do with HIV/AIDS, diabetes, cancer, etc)

http://www.ninds.nih.gov/disorders/peri ... opathy.htm


What is peripheral neuropathy?

Peripheral neuropathy describes damage to the peripheral nervous system, the vast communications network that transmits information from the brain and spinal cord (the central nervous system) to every other part of the body. Peripheral nerves also send sensory information back to the brain and spinal cord, such as a message that the feet are cold or a finger is burned. Damage to the peripheral nervous system interferes with these vital connections. Like static on a telephone line, peripheral neuropathy distorts and sometimes interrupts messages between the brain and the rest of the body.

Because every peripheral nerve has a highly specialized function in a specific part of the body, a wide array of symptoms can occur when nerves are damaged. Some people may experience temporary numbness, tingling, and pricking sensations (paresthesia), sensitivity to touch, or muscle weakness. Others may suffer more extreme symptoms, including burning pain (especially at night), muscle wasting, paralysis, or organ or gland dysfunction. People may become unable to digest food easily, maintain safe levels of blood pressure, sweat normally, or experience normal sexual function. In the most extreme cases, breathing may become difficult or organ failure may occur.

Some forms of neuropathy involve damage to only one nerve and are called mononeuropathies. More often though, multiple nerves affecting all limbs are affected-called polyneuropathy. Occasionally, two or more isolated nerves in separate areas of the body are affected-called mononeuritis multiplex.

In acute neuropathies, such as Guillain-Barré syndrome, symptoms appear suddenly, progress rapidly, and resolve slowly as damaged nerves heal. In chronic forms, symptoms begin subtly and progress slowly. Some people may have periods of relief followed by relapse. Others may reach a plateau stage where symptoms stay the same for many months or years. Some chronic neuropathies worsen over time, but very few forms prove fatal unless complicated by other diseases. Occasionally the neuropathy is a symptom of another disorder.

How are the peripheral neuropathies classified?

More than 100 types of peripheral neuropathy have been identified, each with its own characteristic set of symptoms, pattern of development, and prognosis. Impaired function and symptoms depend on the type of nerves-motor, sensory, or autonomic-that are damaged. Motor nerves control movements of all muscles under conscious control, such as those used for walking, grasping things, or talking. Sensory nerves transmit information about sensory experiences, such as the feeling of a light touch or the pain resulting from a cut. Autonomic nerves regulate biological activities that people do not control consciously, such as breathing, digesting food, and heart and gland functions. Although some neuropathies may affect all three types of nerves, others primarily affect one or two types. Therefore, doctors may use terms such as predominantly motor neuropathy, predominantly sensory neuropathy, sensory-motor neuropathy, or autonomic neuropathy to describe a patient's condition.

What are the symptoms of peripheral nerve damage?

Symptoms are related to the type of affected nerve and may be seen over a period of days, weeks, or years.Muscle weakness is the most common symptom of motor nerve damage. Other symptoms may include painful cramps and fasciculations (uncontrolled muscle twitching visible under the skin), muscle loss, bone degeneration, and changes in the skin, hair, and nails. These more general degenerative changes also can result from sensory or autonomic nerve fiber loss.

Sensory nerve damage causes a more complex range of symptoms because sensory nerves have a wider, more highly specialized range of functions. Larger sensory fibers enclosed in myelin (a fatty protein that coats and insulates many nerves) register vibration, light touch, and position sense. Damage to large sensory fibers lessens the ability to feel vibrations and touch, resulting in a general sense of numbness, especially in the hands and feet. People may feel as if they are wearing gloves and stockings even when they are not. Many patients cannot recognize by touch alone the shapes of small objects or distinguish between different shapes. This damage to sensory fibers may contribute to the loss of reflexes (as can motor nerve damage). Loss of position sense often makes people unable to coordinate complex movements like walking or fastening buttons, or to maintain their balance when their eyes are shut. Neuropathic pain is difficult to control and can seriously affect emotional well-being and overall quality of life. Neuropathic pain is often worse at night, seriously disrupting sleep and adding to the emotional burden of sensory nerve damage.

Smaller sensory fibers without myelin sheaths transmit pain and temperature sensations. Damage to these fibers can interfere with the ability to feel pain or changes in temperature. People may fail to sense that they have been injured from a cut or that a wound is becoming infected. Others may not detect pains that warn of impending heart attack or other acute conditions. (Loss of pain sensation is a particularly serious problem for people with diabetes, contributing to the high rate of lower limb amputations among this population.) Pain receptors in the skin can also become oversensitized, so that people may feel severe pain (allodynia) from stimuli that are normally painless (for example, some may experience pain from bed sheets draped lightly over the body).

Symptoms of autonomic nerve damage are diverse and depend upon which organs or glands are affected. Autonomic nerve dysfunction can become life threatening and may require emergency medical care in cases when breathing becomes impaired or when the heart begins beating irregularly. Common symptoms of autonomic nerve damage include an inability to sweat normally, which may lead to heat intolerance; a loss of bladder control, which may cause infection or incontinence; and an inability to control muscles that expand or contract blood vessels to maintain safe blood pressure levels. A loss of control over blood pressure can cause dizziness, lightheadedness, or even fainting when a person moves suddenly from a seated to a standing position (a condition known as postural or orthostatic hypotension).

Gastrointestinal symptoms frequently accompany autonomic neuropathy. Nerves controlling intestinal muscle contractions often malfunction, leading to diarrhea, constipation, or incontinence. Many people also have problems eating or swallowing if certain autonomic nerves are affected.

What causes peripheral neuropathy?

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

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

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

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

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

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

How is peripheral neuropathy diagnosed?

Diagnosing peripheral neuropathy is often difficult because the symptoms are highly variable. A thorough neurological examination is usually required and involves taking an extensive patient history (including the patient’s symptoms, work environment, social habits, exposure to any toxins, history of alcoholism, risk of HIV or other infectious disease, and family history of neurological disease), performing tests that may identify the cause of the neuropathic disorder, and conducting tests to determine the extent and type of nerve damage.

A general physical examination and related tests may reveal the presence of a systemic disease causing nerve damage. Blood tests can detect diabetes, vitamin deficiencies, liver or kidney dysfunction, other metabolic disorders, and signs of abnormal immune system activity. An examination of cerebrospinal fluid that surrounds the brain and spinal cord can reveal abnormal antibodies associated with neuropathy. More specialized tests may reveal other blood or cardiovascular diseases, connective tissue disorders, or malignancies. Tests of muscle strength, as well as evidence of cramps or fasciculations, indicate motor fiber involvement. Evaluation of a patient’s ability to register vibration, light touch, body position, temperature, and pain reveals sensory nerve damage and may indicate whether small or large sensory nerve fibers are affected.

Based on the results of the neurological exam, physical exam, patient history, and any previous screening or testing, additional testing may be ordered to help determine the nature and extent of the neuropathy.

What treatments are available?

No medical treatments now exist that can cure inherited peripheral neuropathy. However, there are therapies for many other forms. Any underlying condition is treated first, followed by symptomatic treatment. Peripheral nerves have the ability to regenerate, as long as the nerve cell itself has not been killed. Symptoms often can be controlled, and eliminating the causes of specific forms of neuropathy often can prevent new damage.

Neuropathic pain is often difficult to control. Mild pain may sometimes be alleviated by analgesics sold over the counter. Several classes of drugs have recently proved helpful to many patients suffering from more severe forms of chronic neuropathic pain. These include mexiletine, a drug developed to correct irregular heart rhythms (sometimes associated with severe side effects); several antiepileptic drugs, including gabapentin, phenytoin, and carbamazepine; and some classes of antidepressants, including tricyclics such as amitriptyline. Injections of local anesthetics such as lidocaine or topical patches containing lidocaine may relieve more intractable pain. In the most severe cases, doctors can surgically destroy nerves; however, the results are often temporary and the procedure can lead to complications.

What research is being done?

The National Institute of Neurological Disorders and Stroke (NINDS), a component of the Federal government's National Institutes of Health (NIH) within the U.S. Department of Health and Human Services, has primary responsibility for research on peripheral neuropathy. Current research projects funded by the NINDS involve investigations of genetic factors associated with hereditary neuropathies, studies of biological mechanisms involved in diabetes-associated neuropathies, efforts to gain greater understanding of how the immune system contributes to peripheral nerve damage, and efforts to develop new therapies for neuropathic symptoms.

Scientists have found that the destructive effects of abnormal immune system activity cause many neuropathies for which a cause could not previously be identified. However, the exact biological mechanisms that lead to this nerve damage are not yet well understood. Many NINDS-sponsored studies are studying inflammatory neuropathies, both in research animals and in humans, to clarify these mechanisms so that therapeutic interventions can be developed.

Neuropathic pain is a primary target of NINDS-sponsored studies aimed at developing more effective therapies for symptoms of peripheral neuropathy. Some scientists hope to identify substances that will block the brain chemicals that generate pain signals, while others are investigating the pathways by which pain signals reach the brain.

Studies of neurotrophic factors represent one of the most promising areas of research aimed at finding new, more effective treatments for peripheral neuropathies. These substances, produced naturally by the body, protect neurons from injury and encourage their survival. Neurotrophic factors also help maintain normal function in mature nerve cells, and some stimulate axon regeneration. Several NINDS-sponsored studies seek to learn more about the effects of these powerful chemicals on the peripheral nervous system and may eventually lead to treatments that can reverse nerve damage and cure peripheral nerve disorders.

So as not to raise false hope, here is a link to a Science-Based Medicine article by Dr. Steven Novella on November 9, 2011:

http://www.sciencebasedmedicine.org/ind ... c-factors/

Scientific medicine is not easy. By this point we have largely picked the low hanging fruit, and continued improvements are mostly incremental and hard won. In order to get the most out of our limited research dollars, and optimize medical practice with the safest and most effective treatments, we need to use all available scientific evidence in the proper way. That is the essence of SBM.

There are those, however, that misuse or abuse the scientific evidence — whether to promote an ideology, out of innocent ignorance, or for nefarious purposes. In order to be truly science-based a medical intervention should be plausible, or at least not implausible, based upon basic science evidence, and it should actually be safe and effective when tested in people. Therefore, medical practices can fail to be scientific for one of two broad reasons: they can be scientifically implausible, or they can lack proper clinical evidence for safety and efficacy (or even have evidence for lack of efficacy). Some modalities (like homeopathy) fail on both counts.

The more pernicious medical claims are those that seem highly plausible, that can be extrapolated from basic science, but simply lack adequate clinical evidence. Stem cell clinics are an example — they can easily dazzle desperate patients with scientific descriptions of how stem cells work, and even cite published basic-science papers showing the potential of this technology. But what they cannot do is provide clinical evidence that the specific intervention they are offering is safe and effective for the specific disease or condition they are treating.

[snip]

Neurotrophic factors are generally proteins that bind to cells and cause them to grow, proliferate, or just maintain their functionality. Some nervous system cells would die without a steady supply of the needed neurotrophic factors. The discovery of neurotrophic factors and their role in nervous system function was certainly very important to our understanding of neurological diseases. This knowledge has also led to a great deal of speculation about the potential of neurotrophic factors in treating neurological diseases.

After a couple decades of clinical research, however, the reality has not lived up to the promise. As is often the case, highly plausible ideas do not pan out in clinical research. Several neurotrophic factors, for example have been studied in diseases like ALS without any measurable clinical benefit. They are just another reminder that the body is complex, and even when we have a very compelling picture of why a treatment should work, that picture is almost certainly incomplete. We cannot know what the net effect will be of a treatment until we do rigorous clinical trials.

Another way to look at this is that the body has evolved complex mechanisms of self-regulation. It is not easy to push or pull on one piece of this complex system and predict the net effect. There are many reasons why a treatment that we predict should work, doesn’t.

[snip]

Conclusion

The public needs to be aware of the types of misleading claims that are made by clinics, centers, and marketers of health products that can seem very scientific when they are not. The use of pre-clinical evidence to make clinical claims, the use of research methods for clinical diagnosis, and the use of supplements without any consideration of bioavailability are chief among them. Patients and their families are cautioned to be skeptical of any clinic or center that claims to offer a unique service. Further, any clinical claims being made should be backed by well-designed clinical trials of the specific claims published in respected peer-reviewed journals.

Anything less than this is likely to be selling false hope, not a legitimate treatment.

http://www.lymeneteurope.org/forum/viewtopic.php?f=5&t=3629

Politics Ignore Side Effects Of Stavudine

Today's post comes from journaids.org (see link below) and the South African newspaper the Mail and Guardian and talks about decisions being made to buy in the antiretroviral drug stavudine (d4T often called Zerit)). It is claimed that low doses of stavudine are just as effective as tenofovir (one of the bases of Truvada) in suppressing the HIV virus. Stavudine is much much cheaper than tenofovir and therefore seems to make sense if the comparison is true, especially in poorer countries in the third world. However the side effects of stavudine are well-documented and neuropathy caused by stavudine makes hundreds of thousands of people's lives a misery. At the end of the short intro is a link to the full article which is shown as a page of the newspaper - makes interesting reading.

Drug row sparked by HIV spending
Mara Kardas Nelson: Mail and Guardian: 12 July 2013

A new study to be conducted in South Africa, Uganda and India has sparked a heated debate in the HIV activist and research community, demonstrating a divide in strategy at the start of the fourth decade of the epidemic.

The debate has sprung from a clinical trial that aims to see whether low-dose stavudine, or d4T, is as effective as tenofovir, or TDF, one of the antiretrovirals (ARVs) currently recommended for first-line HIV treatment by the World Health Organisation (WHO). d4T was long used as the primary first-line therapy but harsh side effects, including neuropathy (nerve damage) and lipodystrophy (abnormal, sometimes disfiguring, fat distribution), led the WHO to recommend against its use in 2011

It is suggested that TDF or zidovudine (AZT) be used instead. But those drugs are relatively expensive: according to the health advocacy organisation, Médecins Sans Frontières (MSF), d4T is available for as little as $20 (R204) a patient a year, compared with $75 (R764) a patient a year for AZT and $57 (R581) a patient a year for TDF...read the full article

http://www.journaids.org/index.php/blog/blog-entry/drug_row_sparked_by_hiv_spending/

Side Effects of HIV Meds

This is more a general post explaining why HIV medication sometimes causes side effects and what they might be. Of course, neuropathy features strongly amongst those. It's from a U.K. site called 'Positive Gay Guide' (see link below)and is useful background information for any HIV patient.

Side effects of anti-HIV drugs

Side effects from anti-HIV drugs occur either because of an allergic reaction to the drugs, or because of the action of the drugs themselves. HIV enzymes that anti-HIV drugs target are similar to the enzymes your body needs to function normally. When you take anti-HIV drugs they don’t only inhibit the enzymes in HIV, they can also start to affect your body’s own enzymes causing unwanted side effects.

Anti-HIV drugs are very powerful, and so it takes time for your body to adapt to them. There are ways to cope with side effects when they happen. The most common side effects such as nausea or diarrhoea can be managed with anti-nausea or anti-diarrhoea medication. Another common side effect in the short term is a body rash, and this can often be managed with antihistamines. However, a rash can also be a sign of a more serious allergic reaction which we talk more about later on this page. For this reason, if you do get a rash you should go to see your doctor straight away.

Your doctor will use your regular blood tests to monitor you for a wide range of problems that anti-HIV drugs can cause, such as anaemia (which is a deficiency of red blood cells) and kidney or liver toxicity. If the drugs were causing any of these problems then they would be spotted during your routine appointments and blood tests.

Since most side effects disappear after a while many people decide to push through the first month or so, as long as the side effects are not too severe. Make sure you always tell your doctor about any side effects you experience since he or she will need to check that nothing serious is going on.

Obviously, if the side effects are too severe then you and your doctor would want to think about changing one or more of the anti-HIV drugs you are taking to a combination that you would find easier to tolerate.

We talk more about this in the section on changing treatment.

It’s important to note here that you should never just stop taking your anti-HIV drugs, even if the side effects are really bad, without the advice of your HIV doctor. He or she will be able to tell you how to change to a different combination with minimal risk of developing drug resistance to your anti-HIV drugs.

Drinking alcohol or taking certain recreational drugs can make side effects more severe. For instance, ecstasy can increase the levels of the protease inhibitors in your blood. This would increase the chance that you would experience severe side effects.

You can read more about alcohol and recreational drugs and how they can affect HIV and HIV treatment in the section on looking after yourself.

Severe allergic reactions

More serious side effects of anti-HIV drugs can be caused by allergic reactions to certain drugs. One of these is caused by abacavir in 4% to 8% of people who take it, and is known as a hypersensitivity reaction. There is now a genetic test which shows whether you are likely to get this reaction, although the test may not be available everywhere. If you are thinking of taking abacavir, ask your doctor about this test.

Abacavir hypersensitivity reaction usually occurs within the first 6 weeks of treatment, however it can occur at any time and so people taking abacavir are advised to carry a warning card in their wallets. All boxes of abacavir, Kivexa or Trizivir (which both contain abacavir) have a pull out warning card which you should carry with you.

The symptoms of hypersensitivity reaction get steadily worse over a few days and can include a rash, fever, gastrointestinal problems, nausea and vomiting. If you develop these symptoms after starting abacavir you should go to see your doctor immediately. If you were diagnosed with a hypersensitivity reaction then your doctor would ask you to stop taking abacavir. Once you have stopped taking abacavir you must never take it again. Taking abacavir again after you had a hypersensitivity reaction the first time can lead to a very quick and severe allergic reaction which can be fatal.

Metabolic changes

Metabolic changes refer to changes to certain chemical or physical processes used by your body, such as the way it converts fat into energy. Your doctor will keep an eye on certain indicators of metabolic changes each time you have your regular blood tests, such as your cholesterol levels.

It’s unclear why some people experience metabolic changes when taking anti-HIV drugs, however those that have been seen in people with HIV include high cholesterol, diabetes and insulin resistance, high blood sugar and high blood fats (which can be related to body fat changes, and we talk about these later on this page).

If your blood tests indicate that you are experiencing problems with metabolic changes, your doctor may recommend changing the combination of drugs you are taking to one that your body will be better able to cope with. Your doctor may also recommend that you alter your diet to help with problems such as high cholesterol or he may even suggest that you exercise more often.

You can read more about your diet and exercise in the section on looking after yourself.

Body fat changes

A long-term side effect that has been associated with certain anti-HIV drugs is lipodystrophy and lipoatrophy. Lipodystrophy is fat redistribution around the body, usually fat gain around the abdomen. Lipoatrophy is fat loss from parts of the body, often seen as facial wasting or wasting from the arms and legs. These side effects can often be managed with appropriate anti-HIV drug choices, however if you have resistance to some anti-HIV drugs your options may be limited and you may not be able to avoid the drugs that could cause lipodystrophy and lipoatrophy. Protease inhibitors have more commonly been associated with fat redistribution around the abdomen, whereas the NRTIs such as d4T, ddI and AZT have been associated with fat loss. However, other factors are also likely to contribute to lipodystrophy and lipoatrophy, including HIV infection itself.1

If you are having problems with lipodystrophy or lipoatrophy then you and your doctor could think about changing the combination of anti-HIV drugs you are taking. For example, it has been shown that men who have lost fat from their face because of taking the NRTI d4T can actually start to regain some of the lost fat when switching from d4T to abacavir, another NRTI.2

There are also reconstructive treatments for people with facial wasting. One of these is polylactic acid, also known as New Fill or Sculptra. This is given as injections into the areas on the face where fat has been lost, and it helps to stimulate collagen growth and increase the skin thickness. This is a very safe treatment, and has been shown to greatly improve the quality of life of men in a number of studies.3 However it’s not available everywhere on the NHS, and even where it is there could be a long waiting list. Speak to your doctor if you think you may be interested in finding out more.

Peripheral neuropathy

Another long term side effect of certain anti-HIV drugs is peripheral neuropathy. This is a painful condition caused by damage to the peripheral nerves, usually in the feet, legs and hands. It’s often described as feeling like burning pins and needles, and can range from mild tingling and numbness to very intense pain.

The drugs that have been associated with peripheral neuropathy are the NRTIs d4T, ddI and to a lesser extent 3TC, however peripheral neuropathy can also be caused by HIV itself. Alcohol and some recreational drugs are neurotoxins, meaning that they are toxic to the nervous system. Taking recreational drugs, such as amphetamines or cocaine, or drinking too much can make peripheral neuropathy worse.

If you do develop peripheral neuropathy from your anti-HIV drugs you and your doctor would want to change the combination of drugs you are taking if possible.

If you aren’t taking any of the drugs that are associated with peripheral neuropathy or the condition continues after stopping the drugs which could cause it, it may be that there’s another cause. Your doctor would probably do a blood test to check your vitamin B12 levels, as a B12 deficiency can cause neuropathy. It could also be HIV itself that’s the cause.

There are some treatment options available for peripheral neuropathy. The anti-convulsant drug gabapentin has been shown to improve the condition in some people, but not all. Other treatments include a low dose of amitriptyline, a drug normally used to treat depression, and acetyl-l-carnitine, an amino acid which may actually reverse the nerve damage seen in people with peripheral neuropathy. However, medical opinion is divided about how effective these and other treatments for neuropathy are. If you are experiencing pain from peripheral neuropathy that isn’t caused by any anti-HIV drugs you are taking, you could ask your doctor to refer you to a specialist neurologist who can investigate the causes further.

If you are in quite a lot of pain then you could also ask to be referred to a specialist in pain management or palliative care who will explore with you different ways to manage the pain you are in. It may be worth asking about trying a Transcutaneous Electrical Nerve Stimulator, more commonly referred to as a TENS machine. This passes a small electric current through your nerves and has been shown to be beneficial to people experiencing neuropathic pain.

You can find more information about the side effects of the specific anti-HIV drugs you are taking, or thinking of taking, on NAM’s website, Aidsmap.

http://www.gmfa.org.uk/positive/hiv-treatment/side-effects