ANTIVIRAL THERAPY BENEFITS HIV INFECTED STIMULANT USERS

New clinical research from UC San Francisco shows that 341 HIV-infected men who reported using stimulants such as methamphetamine or cocaine derived life-saving benefits from being on antiretroviral therapy that were comparable to those of HIV-infected men who do not use stimulants.

That said, those who reported using stimulants at more than half of at least two study visits did have modestly increased chances of progressing to AIDS or dying after starting antiretroviral therapy compared to non-users. The data was collected between 1996 and 2012.

"Patients with HIV who use stimulants and other substances often experience difficulties with accessing antiretroviral therapy, partially due to the concerns of healthcare providers that they will not be able take their medications as directed. Findings from this study demonstrate that many stimulant users take their antiretroviral therapy at levels sufficient to avoid negative clinical outcomes. When we look at overall mortality, antiretroviral therapy leads to similar clinical benefits for both stimulant users and non-users, notwithstanding stimulant use," said the study's primary investigator, Adam W. Carrico, PhD., UCSF assistant professor of nursing.

The research is available starting in October online ahead of print in the Journal of Acquired Immune Deficiency Syndromes. The study included 1,313 HIV-infected men who have sex with men within the Multicenter AIDS Cohort Study, an ongoing nationwide prospective study of HIV infection among men who have sex with men in the U.S.

"If we are to achieve the goals of the President's National HIV/AIDS Strategy and UNAIDS to end the HIV/AIDS epidemic, we will need to treat HIV-positive active substance users for their HIV while encouraging them to stop or reduce their substance use. Programs integrating substance abuse services with HIV clinical care may both improve health outcomes for patients and reduce new infections," said Carrico.

The UCSF Division of HIV/AIDS at San Francisco General Hospital has created an integrated care delivery system that could serve as a model for other clinics, added Carrico. The HIV primary care clinic utilizes a patient centered team care approach that includes substance abuse services for stimulant and opioid users, along with mental health services, all located onsite. STOP, the "stimulant treatment outpatient program," within the clinic provides outpatient substance abuse and mental health treatment integrated with patients' primary medical care.

"The pattern of use varies and the real issue is whether patients can take their antiretrovirals as prescribed. We find that some patients are able to start taking antiretrovirals very reliably before they are able to decrease or stop their stimulant use, which often requires more complex behavioral, emotional, interpersonal and environmental changes. Being in an HIV primary care setting allows us to engage stimulant users even if they are not ready to go to specialty substance abuse programs or support groups," said Valerie Gruber, PhD, STOP director and UCSF professor of psychiatry.

All You Need To Know About HIV And Pain

Well not quite all and despite this being an earlier article, updated in June 2012,  they still don't issue any information about the fact that Lyrica (Pregabalin) has been withdrawn for HIV-related pain by the company that makes it. However, for the rest, this comprehensive article from aidsetc.org (see link below) is about as good an overview as you can find. As they say, 30% to 60% of HIV patients experience some degree of pain related to their condition, so well-explained articles like this are essential for people trying to put two and two together and not come up with five. If, for instance, you've just realised that your neuropathic symptoms are not just a temporary irritation, you may be looking for information that gives a solid framework to what you're feeling - this article will help you make sense of what's happening.

Pain Syndrome and Peripheral Neuropathy

Guide for HIV/AIDS Clinical Care, HRSA HIV/AIDS Bureau

June 2012

Background

The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage." Pain is subjective, it is whatever the patient says it is, and it exists whenever the patient says it does. Pain is a common symptom in people with HIV infection, especially those with advanced disease. It occurs in 30-60% of HIV/AIDS patients and can diminish their quality of life significantly. Like cancer patients, HIV patients experience an average of 2.5 to 3 types of pain at once. Pain in HIV-infected patients may have many causes (as discussed below).

Peripheral Neuropathy

Pain from HIV-associated peripheral neuropathy is particularly common, and may be debilitating. Peripheral neuropathy is clinically present in approximately 30% of HIV-infected individuals and typically presents as distal sensory polyneuropathy (DSP). It may be related to HIV itself (especially at CD4 counts of <200 cells/µL), to medication toxicity (e.g., from certain nucleoside analogues such as stavudine or didanosine), or to the effects of chronic illnesses (e.g., diabetes mellitus). Patients with peripheral neuropathy may complain of numbness or burning, a pins-and-needles sensation, shooting or lancinating pain, and a sensation that their shoes are too tight or their feet are swollen. These symptoms typically begin in the feet and progress upward; the hands may be affected. Patients may develop difficulty walking because of discomfort, or because they have difficulty feeling their feet on the ground. Factors associated with increased risk of peripheral neuropathy include the following:

• Previous peripheral neuropathy
• Low CD4 count (<200 cells/µL)
• Previous AIDS-defining opportunistic infection or neoplasm
• Vitamin B12 deficiency
• Exposure to stavudine or didanosine
• Use of other drugs associated with peripheral neuropathy (e.g., isoniazid, dapsone, metronidazole, hydroxyurea, thalidomide, linezolid, ribavirin, vincristine)
• Use of other neurotoxic agents (e.g., alcohol)
• Diabetes mellitus

Patients should be assessed carefully before the introduction of a potentially neurotoxic medication (including stavudine or didanosine), and the use of these medications for patients at high risk of developing peripheral neuropathy should be avoided.

Pain is significantly undertreated, especially among HIV-infected women, because of factors ranging from providers' lack of knowledge about the diagnosis and treatment of pain to patients' fear of addiction to analgesic medications. Pain, as the so-called fifth vital sign, should be assessed at every patient visit.

S: Subjective

Self-report is the most reliable method to assess pain.

The patient complains of pain. The site and character of the pain will vary with the underlying cause. Ascertain the following from the patient:

• Duration, onset, progression
• Distribution, symmetry
• Character or quality (e.g., burning, sharp, dull)
• Intensity
• Severity (using the 0-10 scale; see Figure 1)
• Neurologic symptoms (e.g., weakness, cranial nerve abnormalities, bowel or bladder abnormalities)
• Exacerbating or relieving factors
• Response to current or past pain management strategies
• Past medical history (e.g., AIDS, diabetes mellitus)
• Psychosocial history
• Substance abuse and alcohol use history (amount, duration)
• Medications, current and recent (particularly zalcitabine, didanosine, stavudine, and isoniazid)
• Nutrition (vitamin deficiencies)
• Meaning of the pain to the patient

Measuring the severity of the pain: Have the patient rate the pain severity on a numeric scale of 0-10 (0 = no pain; 10 = worst imaginable pain), a verbal scale (none, small, mild, moderate, or severe), or a pediatric faces pain scale (when verbal or language abilities are absent). Note that pain ratings >3 usually indicate pain that interferes with daily activities. Use the same scale for evaluation of treatment response.

Figure 1. Faces Pain Rating Scale (0-10)

Quick screen for peripheral neuropathy: Ask about distal numbness and check Achilles tendon reflexes. Screening for numbness and delayed or absent ankle reflexes has the highest sensitivity and specificity among the clinical evaluation tools for primary care providers. For a validated screening tool, use the ACTG Brief Peripheral Neuropathy Scale (BPNS) to scale and track the degree of peripheral neuropathy.

O: Objective

Measure vital signs (increases in blood pressure, respiratory rate, and heart rate can correlate with pain). Perform a symptom-directed physical examination, including a thorough neurologic and musculoskeletal examination. Look for masses, lesions, and localizing signs. Pay special attention to sensory deficits (check for focality, symmetry, and distribution [such as "stocking-glove"]), muscular weakness, reflexes, and gait. Patients with significant motor weakness or paralysis, especially if progressive over days to weeks, should be evaluated emergently.

To evaluate peripheral neuropathy: Check ankle Achilles tendon reflexes and look for delayed or absent reflexes as signs of peripheral neuropathy. Distal sensory loss often starts with loss of vibratory sensation, followed by loss of temperature sensation, followed by onset of pain. Findings are usually bilateral and symmetric.

A: Assessment

Pain assessment includes determining the type of pain, for example, nociceptive, neuropathic, or muscle spasm pain.

Nociceptive pain occurs as a result of tissue injury (somatic) or activation of nociceptors resulting from stretching, distention, or inflammation of the internal organs of the body. It usually is well localized; may be described as sharp, dull, aching, throbbing, or gnawing in nature; and typically involves bones, joints, and soft tissue.

Neuropathic pain occurs from injury to peripheral nerves or central nervous system structures. Neuropathic pain may be described as burning, shooting, tingling, stabbing, or like a vise or electric shock; it involves the brain, central nervous system, nerve plexuses, nerve roots, or peripheral nerves. It is associated with decreased sensation and hypersensitivity.

Muscle spasm pain can accompany spinal or joint injuries, surgeries, and bedbound patients. It is described as tight, cramping, pulling, and squeezing sensations.

Although pain in HIV-infected patients often results from opportunistic infections, neoplasms, or medication-related neuropathy, it is important to include non-HIV-related causes of pain in a differential diagnosis. Some of these other causes may be more frequent in HIV-infected individuals. A partial list for the differential diagnosis includes:

• Anorectal carcinoma
• Aphthous ulcers
• Appendicitis
• Arthritis, myalgias
• Candidiasis, oral or esophageal
• Cholecystitis
• Cryptococcal disease
• Cytomegalovirus colitis
• Dental abscesses
• Gastroesophageal reflux disease (GERD)
• Ectopic pregnancy
• Herpes simplex
• Herpes zoster
• Kaposi sarcoma
• Lymphoma
• Medication-induced pain syndromes (e.g., owing to growth hormone, granulocyte colony-stimulating factor)
• Medication-induced peripheral neuropathy (e.g., owing to didanosine, stavudine, isoniazid, vincristine)
• Other causes of peripheral neuropathy: diabetes, hypothyroidism, B12 deficiency, syphilis, cryoglobulinemia (especially in patients with hepatitis C coinfection)
• Mycobacterium avium complex
• Myopathy
• Pancreatitis
• Pelvic inflammatory disease
• Toxoplasmosis

P: Plan

Perform a diagnostic evaluation based on the suspected causes of pain.

Treatment

Treatment should be aimed at eliminating the source of pain, if possible. If symptomatic treatment of pain is needed, begin treatment based on the patient's pain rating scale, using the least invasive route. The goal is to achieve optimal patient comfort and functioning (not necessarily zero pain) with minimal medication adverse effects, negotiated with the patient. Use the three-step pain analgesic ladder originally devised by the World Health Organization (WHO); see Figure 2.

Nonpharmacologic interventions

The following interventions can be used at any step in the treatment plan:

• A therapeutic provider-patient relationship
• Physical therapy
• Exercise
• Relaxation techniques
• Guided imagery
• Massage
• Biofeedback
• Reflexology
• Acupuncture
• Thermal modalities (hot and cold compresses or baths)
• Transcutaneous electrical nerve stimulation (TENS)
• Spiritual exploration
• Prayer
• Deep breathing
• Meditation
• Enhancement of coping skills
• Self-hypnosis
• Humor
• Distraction
• Hobbies

Pharmacologic interventions

Principles of pharmacologic pain treatment

• The dosage of the analgesic is adjusted to give the patient adequate pain control.
• The interval between doses is adjusted so that the pain control is uninterrupted. It can take 4-5 half-lives before the maximum effect of an analgesic is realized.
• Chronic pain is more likely to be controlled when analgesics are dosed on a continuous schedule rather than "as needed." Sustained-release formulations of opioids should be used whenever possible.
• For breakthrough pain, use "as needed" medications in addition to scheduled-dosage analgesics. When using opiates both for scheduled analgesia for breakthrough pain, a good rule of thumb is to use 10% of the total daily dosage of opiates as the "as needed" opiate dose for breakthrough pain.
• Oral administration has an onset of analgesia of about 20-60 minutes, tends to produce more stable blood levels, and is cheaper.
• Beware of the risk of prolonged analgesic half-lives in patients with renal or hepatic dysfunction.
• Caution when using combination analgesics that are coformulated with ingredients such as acetaminophen, aspirin, or ibuprofen. Determine the maximum daily dosage of all agents.

The following three steps are adapted from the WHO analgesic ladder. Agents on higher steps are progressively stronger pain relievers but tend to have more adverse effects.

Figure 2. Pharmacologic Approaches to Pain Management: WHO Three-Step Ladder

Adapted from World Health Organization. Cancer Pain Relief and Palliative Care, Report of a WHO Expert Committee. Geneva: World Health Organization; 1990.

Note: "Adjuvants" refers either to medications that are coadministered to manage an adverse effect of an opioid or to so-called adjuvant analgesics that are added to enhance analgesia.

Step 1: Nonopiates for mild pain (pain scale 1-3)

• The most common agents in this step include acetaminophen (650-1,000 mg PO Q6H as needed) and nonsteroidal antiinflammatory drugs (NSAIDs) such as ibuprofen 600-800 mg PO TID with food, and cyclooxygenase-2 (COX-2) inhibitors such as celecoxib and rofecoxib.
• A proton-pump inhibitor (such as omeprazole) can decrease the risk of gastrointestinal bleeding when using NSAIDs.
• Acetaminophen has no effect on platelets and no antiinflammatory properties; avoid use in patients with hepatic insufficiency, and in general limit to 4 g per day in acute use (or 2 g per day for patients with liver disease). Monitor liver function tests in chronic use.
• NSAIDs and acetaminophen can be used together for synergism.
• Note that COX-2 inhibitors have been associated with an increased risk of cardiovascular events and should be used with caution.

Step 2: Mild opiates with or without nonopiates for moderate pain (pain scale 4-6)

• Most agents used to treat moderate pain are combinations of opioids and Step 1 agents. The most common agents are acetaminophen combined with codeine, oxycodone, or hydrocodone. Codeine can be dosed as codeine sulfate, separately from acetaminophen. Beware of acetaminophen toxicity in these combination drugs.
• Other agents include buprenorphine (partial opiate agonist).
• Tramadol (Ultram) is a centrally acting nonopiate that can be combined with NSAIDs. As with opiates, it is prone to abuse. Tramadol lowers the seizure threshold; avoid use for patients with a seizure history. Avoid coadministration with selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) because of the risk of serotonin syndrome.

Step 3: Opioid agonist drugs for severe pain (pain scale 7-10)

• Morphine is the drug of choice in this step. Start with short-acting morphine and titrate the dosage to adequate pain control, then divide the 24-hour total in half to determine the dosing for the sustained-release morphine, given Q12H. When converting from IV to PO morphine, PO dosage is about two to three times the parenteral dose.
• Other agents used are oxycodone, hydromorphone, fentanyl, levorphanol, methadone, codeine, hydrocodone, oxymorphone, and buprenorphine.
• Avoid meperidine because of the increased risk of delirium and seizures.
• Around-the-clock, sustained-release PO dosing will achieve optimum pain relief.
• Patients unable to take PO therapy may use transdermal fentanyl patches or do rectal administration of sustained-release tablets such as long-acting morphine. Note that the onset of analgesia with fentanyl patches can take more than 12 hours, and the analgesic effect can last more than 18 hours after the patch is removed.
• Anticipate and treat complications and adverse effects of opioid therapy, such as nausea, vomiting, and constipation. Constipation often leads to nausea and can be prevented with prophylactic stool softeners (such as docusate) and stimulant laxatives (such as senna).

Adjunctive treatments

The addition of antidepressant medications can improve pain management, especially for chronic pain syndromes. These agents, and anticonvulsants, usually are used to treat neuropathic pain (discussed in more detail below), but should be considered for treatment of other chronic pain syndromes as well.

Treatment of neuropathic pain

Assess the underlying etiology, as discussed above, and treat the cause as appropriate. Review the patient's medication list for medications that can cause neuropathic pain. Discontinue the offending agents, if possible. For patients on stavudine or didanosine, in particular, switch to another nucleoside analogue if suitable alternatives exist, or at least consider dosage reduction of stavudine to 30 mg BID (consult with an HIV expert). For patients on isoniazid, ensure that they are taking vitamin B6 (pyridoxine) regularly to avoid isoniazid-related neuropathy.

Nonpharmacologic interventions for neuropathic pain

The nonpharmacologic interventions described above can be useful in treating neuropathic pain.

Pharmacologic interventions for neuropathic pain

Follow the WHO ladder of pain management described above. If Step 1 medications are ineffective, consider adding antidepressants, anticonvulsants, or both before moving on to opioid treatments.

Antidepressants

Antidepressant medications often exert analgesic effects at dosages that are lower than those required for antidepressant effects. As with antidepressant effects, optimum analgesic effects may not be achieved until several weeks after starting therapy.

• Tricyclic antidepressants (TCAs): Note that ritonavir and other protease inhibitors may increase the level of TCAs, so start at the lowest dosage and titrate up slowly. Dosages may be titrated upward every 3-5 days, as tolerated. In general, use lower dosages for elderly patients, up to 100 mg QHS.
  • Nortriptyline (Pamelor): Starting dosage is 10-25 mg QHS. Usual maintenance dosage is 20-150 mg QHS.
  • Desipramine (Norpramin): Starting dosage is 25 mg QHS. Usual maintenance dosage is 25-250 mg QHS.
  • Imipramine: Starting dosage is 25 mg QHS. Usual maintenance dosage is 25-300 mg QHS.
  • Amitriptyline (Elavil): Starting dosage is 10-25 mg QHS. Usual maintenance dosage is 25-150 mg QHS. Amitriptyline has the highest rate of adverse effects among the TCAs, so other agents typically are preferred.
  Adverse effects include sedation, anticholinergic effects (e.g., dry mouth, urinary retention), QT prolongation, arrhythmias, and orthostatic hypotension. Monitor TCA levels and EKG at higher dosage levels. There is a risk of overdose if taken in excess.
• SSRIs: See chapter Major Depression and Other Depressive Disorders for dosing, side effects, and drug interactions associated with this class of agents. SSRIs are less effective than TCAs in treating chronic pain.
• Venlafaxine (Effexor): Starting dosage is 37.5 mg daily. Usual maintenance dosage is 75-300 mg daily in divided doses or by extended-release formulation (Effexor XR). Note that there are limited data on using venlafaxine for patients with HIV infection.
• Duloxetine (Cymbalta): Starting dosage is 30-60 mg daily. Dosages of >60 mg per day are rarely more effective for either depression or pain treatment. Note that there are limited data on using duloxetine for patients with HIV infection.

Anticonvulsants

The following agents may be effective for neuropathic pain:

• Gabapentin (Neurontin): Considered first-line for HIV sensory neuropathy for its tolerability. Starting dosage is 100-300 mg QHS; may be increased every 3-5 days to BID or TID to achieve symptom relief. Monitor response and increase the dosage every 1-2 weeks by 300-600 mg/day. Usual maintenance dosage is 1,200-3,600 mg/day in divided doses. Adverse effects include somnolence, dizziness, fatigue, weight gain, and nausea. To discontinue, taper over the course of 7 or more days.
• Pregabalin (Lyrica): Starting dosage is 25-50 mg TID; may be increased by 25-50 mg per dose every 3-5 days as tolerated to achieve symptom relief. Maximum dosage is 200 mg TID. Adverse effects are similar to those of gabapentin. To discontinue, taper over the course of 7 or more days.
• Lamotrigine (Lamictal): Starting dosage is 25 mg QOD; titrate slowly to 200 mg BID over the course of 6-8 weeks to reduce the risk of rash (including Stevens-Johnson syndrome). Adverse effects include sedation,dizziness, ataxia, confusion, nausea, blurred vision, and rash. Note that lopinavir/ritonavir (Kaletra) may decrease lamotrigine levels; higher dosages may be needed. To discontinue, taper over the course of 7 or more days.
• Although phenytoin and carbamazepine have some effectiveness in treating neuropathy, they have significant drug interactions with protease inhibitors and nonnucleoside reverse transcriptase inhibitors, and their use with HIV-infected patients is limited. Topiramate and valproic acid have been used for migraine prophylaxis and anecdotally may be useful for treating peripheral neuropathy, but have not been well-studied in HIV-related neuropathies.

Treatment of Muscle Spasm Pain

Stretching, heat, and massage may help the pain of muscle spasm. This pain also can respond to muscle relaxants such as baclofen, cyclobenzaprine, tizanidine, benzodiazepines, as well as intraspinal infusion of local anesthetics for spinal injuries.

Substance Abuse, HIV, and Pain

Some health care providers hesitate to treat pain in patients with current or past substance abuse because of concern about worsening these patients' dependence on opioids or suspicion that such patients are seeking pain medications for illicit purposes. However, the following points should be considered:

• Many patients with current or past substance abuse do experience pain, and this pain should be evaluated by care providers and treated appropriately.
• Failure to distinguish among addiction, tolerance, and dependence can lead to undertreatment of chronic pain by health care providers.
• Addiction (substance abuse) is a complex behavioral syndrome characterized by compulsive drug use for the secondary gain of euphoria.
• Pharmacologic tolerance refers to the reduction of effectiveness, over time, of a given dosage of medication.
• Physical dependence is the consequence of neurophysiologic changes that take place in the presence of exogenous opioids.
• Aberrant use of pain medications, if it develops, is best managed by an interdisciplinary team of providers from HIV clinical care, psychiatry, psychology, pharmacy, social services, and drug addiction management.
• Drug-drug interactions between certain antiretroviral medications and methadone can decrease methadone serum concentrations (see chapter Drug-Drug Interactions with HIV-Related Medications). If this occurs, methadone dosages may need to be increased to prevent opiate withdrawal.
• As part of chronic pain management in patients with substance abuse, consider establishing a written pain-management contract to be signed by the clinician and the patient. The contract should:
  • Clearly state limits and expectations for both the patient and provider.
  • Identify a single clinician responsible for managing the pain regimen.
  • Tell the patient what to do if the pain regimen is not working.
  • Describe the procedure for providing prescriptions (e.g., one prescription given to the patient, in person, for a limited period of time, such as 1 month).
  • List the rules for dealing with lost medications or prescriptions.

Patient Education

• Pain management is part of HIV treatment, and patients should give feedback to allow the best treatment decisions. If pain persists for more than 24 hours at a level that interferes with daily life, patients should inform their health care provider so that the plan can be changed and additional measures, if needed, can be tried.
• Patients should not expect full pain relief in most cases, but enough relief that they can perform their daily activities.
• "Mild" pain medications (e.g., NSAIDs, aspirin, acetaminophen) usually are continued even after "stronger" medications are started because their mechanism of action is different from that of opiates. This combination of pain medication has additive effects, so that pain may be controllable with a lower narcotic dosage.
• Patients taking "around-the-clock" medications, should take them on schedule. Those taking "as needed" medications should take them between doses only if they have breakthrough pain.
• Opiates may cause severe constipation. Patients must remain hydrated and will likely need stool softeners, laxatives, or other measures. They should contact their health care provider promptly if constipation occurs.
• Patients should avoid use of recreational drugs and alcohol when taking opiates because opiates can interact with them or cause additive adverse effects, possibly resulting in central nervous system depression, coma, or death.
• Patients taking opiates should avoid driving and operating machinery.

http://www.aidsetc.org/aidsetc?page=cg-801_pain

Neuropathy HIV And Foot Care

Today's post from journals.lww.com (see link below) is a very thorough examination of the relationship between HIV and neuropathy and how as a result, foot care is often overlooked in neuropathy patients. It provides relatively easy explanations for the damage process caused by either the virus itself or the medication used to treat it but misses out on the fact that HIV patients can also have other problems which may bring on neuropathy (cancer, diabetes for instance). The article goes on to provide some helpful advice as to how people should look after their feet, especially when there's a loss of feeling involved and all in all, is well worth reading, for all people living with neuropathy.

 

HIV Peripheral Neuropathy and Foot Care Management: A Review of Assessment and Relevant Guidelines
AJN, American Journal of Nursing:
December 2013 - Volume 113 - Issue 12 - p 34–40
Feature Articles
Anastasi, Joyce K. PhD, DrNP; Capili, Bernadette PhD, NP-C; Chang, Michelle MS

Author Information

Joyce K. Anastasi is an Independence Foundation endowed professor and founding director of the Division of Special Studies in Symptom Management (DS3M) at the New York University College of Nursing in New York City, where Bernadette Capili is an assistant professor and associate director of the DS3M, and Michelle Chang is a research associate at the DS3M. Contact author: Joyce K. Anastasi, ja2188@nyu.edu. The authors and planners have disclosed no potential conflicts of interest, financial or otherwise.

Abstract

Overview: Despite the decline in the incidence of central nervous system disease associated with HIV, distal sensory peripheral (DSP) neuropathy continues to be prevalent in this population, causing debilitating symptoms and affecting quality of life. Patients typically present with numbness, tingling, burning pain, and loss of sensation in the toes and soles of their feet. Although this complication causes loss of protective function and puts patients at elevated risk for injury, infection, and falls, foot care for people with HIV is often overlooked. This article reviews what is known about DSP neuropathy in HIV and discusses relevant foot care guidelines, adopted from the literature on other conditions associated with neuropathic foot disorders.

Peripheral neuropathy, a condition characterized by damaged sensory or motor peripheral nerves, may cause pain, sensory loss, or muscle weakness. Peripheral neuropathy may develop as a result of diabetes, physical injury, tumors, certain medications, heavy alcohol use, certain inherited disorders, autoimmune disease, vitamin deficiencies, and such infectious diseases as HIV.1 The prevalence of distal sensory peripheral (DSP) neuropathy (often referred to as distal symmetric polyneuropathy or distal sensory polyneuropathy) in HIV patients is estimated to range from 38% to 44%.2, 3

Presenting symptoms of DSP neuropathy in HIV typically include bilateral and symmetric tingling, burning, or loss of feeling in the toes and soles of the feet. Symptoms tend to start at the toes and travel up the feet to the ankles and, eventually, to the lower legs, a pattern known as a “stocking” distribution. Common signs include decreased or absent ankle reflexes, impaired pain and temperature perception, reduced or absent vibration sensation in the toes, and occasional intrinsic muscle weakness.4, 5 Patients may experience loss of balance, leading to falls, or have difficulty walking, bathing, or dressing. The symptoms can cause extreme discomfort, affecting employment, emotional health, independence, and quality of life.2

Foot care for people living with HIV is often overlooked as a clinical issue. HIV interferes with the body's immune system, increasing the risk of acquiring infections. Decreased sensation in the feet may lead to injuries and infections that go unnoticed. Tinea pedis (athlete's foot, a fungal infection that causes itching, scaling, blistering, and fissuring of the skin of the feet), onychomycosis (a fungal infection of the nail), and paronychia (a fungal or bacterial infection of the skin at the edge of the nail) frequently affect people who are immunocompromised and thus more prone to developing secondary systemic infections.6-8 In one study, the prevalence of onychomycosis among 500 people with HIV was 23%.7 Both onychomycosis and tinea pedis may lead to lower-extremity bacterial cellulitis.

For patients with diabetes, foot care guidelines and educational materials are ubiquitous. Although there are no specific foot care recommendations for people living with HIV, many of the principles guiding the care of patients with diabetes or cancer apply to this population as well. In this article, we integrate what is currently known about DSP neuropathy in HIV patients with the relevant guidelines for the management of other conditions that similarly render patients susceptible to neuropathic foot disorders.

PATHOPHYSIOLOGY

DSP neuropathy may be associated with the HIV infection itself or with antiretroviral toxicity. The condition is believed to be linked to axonal injury resulting from the binding of the viral envelope glycoprotein 120 to chemokine receptors and to macrophage dysregulation, which prompts the local release of proinflammatory neurotoxic cytokines.9, 10 The drug-associated neuropathies may be mediated by disrupted DNA synthesis, which interferes with mitochondrial function.11 With antiretroviral toxicity, symptom onset tends to be sudden and associated with the start of antiretroviral therapy (ART), usually peaking within the first three months of treatment.12, 13
 
RISK FACTORS

Several factors increase the risk that people with HIV will develop DSP neuropathy and associated foot problems. These include past or current use of neurotoxic drugs, advanced age, metabolic disorders, alcohol use, nutritional deficiencies, and a low CD4+ count.

Neurotoxic drugs. Some nucleoside reverse transcriptase inhibitors (NRTIs) are associated with neuropathy.14, 15 Because they inhibit mitochondrial DNA polymerase gamma, a key enzyme in mitochondrial replication, NRTIs may cause mitochondrial dysfunction, oxidative stress, increased production of free radicals, and tissue injury and toxicity— although other mechanisms likely contribute to the development of DSP neuropathy as well.16, 17 For example, infiltrating activated macrophages, proinflammatory cytokines, and other mediators may play a role in damaging peripheral nerve axons and dorsal root ganglia fibers.18 Of the NRTIs, the dideoxynucleoside NRTIs (d-NRTIs)—didanosine (Videx), zalcitabine (Hivid; taken off the market in 2006), and stavudine (Zerit)—have demonstrated the most mitochondrial toxicity and greatest association with neuropathy. The newer NRTIs demonstrate less toxicity; their association with neuropathy remains unclear.

Although the use of d-NRTIs is being phased out in developed countries, the prevalence of neuropathy remains high.2, 3 These drugs are still widely used in resource-limited regions of the world—particularly stavudine, the component most commonly found in the fixed-dose generic drugs.2 The cumulative, long-term effects of exposure to d-NRTIs are not yet clear.19, 20 A small study of patients with current or prior use of d-NRTI treatment found that subjects who had previously tolerated the drugs without developing neurotoxicity were not at significant risk for developing incident DSP neuropathy.21 Another study found that past, but not current, d-NRTI use was associated with an increased risk of pain in HIV-associated neuropathy after adjusting for other factors.2 Recent research on the potential contribution of protease inhibitors to the risk of neuropathy is inconclusive.22, 23

People living with HIV commonly manage comorbid conditions with multiple drugs, increasing the risk of neurotoxic adverse effects and drug–drug interactions. Drugs with neurotoxic potential frequently used to treat HIV include dapsone (Aczone), hydroxyurea (Droxia, Hydrea), metronidazole (Flagyl and others), vincristine, thalidomide (Thalomid), isoniazid, linezolid (Zyvox), and ribavirin (Rebetol and others).24

Advanced age. The introduction of ART greatly increased the life span of people with HIV, and advanced age has consistently been associated with DSP neuropathy in the eras both preceding and following the introduction of combination ART regimens, most often referred to as highly active ART (HAART).2, 25 As people age, the peripheral nervous system undergoes the following changes26, 27:

* the density of small and large myelinated fibers decreases

* the amplitude of nerve action potentials declines

* nerve conduction slows

By 2015, half of the people living with HIV in the United States will be over age 50.28 With the aging of the HIV population and prolonged exposure to ART, the prevalence and severity of DSP neuropathy is a growing concern.

Metabolic disorders, such as diabetes or impaired glucose tolerance, may further increase the risk of DSP neuropathy. Population studies indicate that neuropathy affects 60% to 70% of patients with type 1 and type 2 diabetes, and risk rises with age and with the duration of diabetes.29 It's been suggested that small-fiber neuropathy may be associated with impaired glucose tolerance and may also occur in prediabetes.30, 31 In both diabetes and HIV, high triglyceride levels are associated with neuropathy,32 and many people with diabetes experience neurovascular damage, which impedes blood flow to the extremities, potentially contributing to or exacerbating symptoms in those who also have HIV and DSP neuropathy.

Data suggest that the increased prevalence of glucose disorders among patients living with HIV is associated with HAART use.33 Individuals using HAART often experience such metabolic complications as lipodystrophy, dyslipidemia, and insulin resistance, which in turn increase their risk of diabetes. New-onset diabetes occurs in an estimated 1% to 6% of HIV-infected people using protease inhibitors.34

Alcohol use and nutritional deficiencies. Some people with HIV try to self-manage their neuropathic symptoms with alcohol or illegal drug use.35, 36 Long-term, heavy alcohol use can damage nerves, while causing deficiencies in the vitamins (particularly B vitamins) and minerals essential to healthy nerve function.37 The effects of nutritional deficiencies may be compounded by weight loss and poor diet, which are common problems in HIV owing to nausea, loss of appetite, diarrhea, and the adverse effects of medications.38, 39 In addition, poor diet may exacerbate impaired immunity, contributing to the progression of HIV and reducing the therapeutic effect of ART.

CD4+ count. Prior to the widespread use of HAART, a higher plasma HIV-1 RNA load and lower CD4+ count were associated with an increased risk of DSP neuropathy.40 In the post-HAART era, however, an elevated viral load no longer seems to be associated with increased risk, although DSP neuropathy remains prevalent among those with advanced, untreated HIV or a lower nadir CD4+ cell count.2
 
ASSESSMENT AND MANAGEMENT

It is useful to determine whether the patient has any neurologic symptoms, such as muscle, bowel, or bladder abnormalities. Documentation should include any history of drug or alcohol abuse, detailing the amount of the substance used and the duration of use; current and past medications; and an assessment of dietary and nutritional deficiencies.

All patients with HIV should receive an annual, comprehensive foot exam in which the skin, hair, nails, musculoskeletal structure, circulation, and sensation of the feet are assessed. Those diagnosed with DSP neuropathy may need more frequent foot exams. Inquire about and document any reports of leg discomfort, providing details about the following factors:

* symptom onset

* location

* duration

* the character or quality of described sensations (for example, whether pain is burning, sharp, or dull)

* the severity (using a 0-to-10-point scale)

* diurnal variation

* progression

* exacerbating or relieving factors

Sensory testing. An assessment should also include sensory testing of the feet. Pressure sensation is assessed using a 5.07 (10-g) Semmes-Weinstein nylon monofilament on the plantar surface of the foot while the patient's eyes are closed (see How to Perform a Pressure Sensory Exam). Practice varies as to the number (one to 10) and location of sites tested for skin breakdown.41 One study found that exams that included the first toe, third metatarsal head, and two other toes or metatarsal heads per foot produced a sensitivity of 90% to 93% for abnormal pressure sensation and required less than one minute to complete.42

Patients are tested for light touch with a cotton swab and for temperature discrimination with warm and cold stimuli. Pinprick sensation is tested using the sharp end of a disposable safety pin. Patients with a loss of protective sensation are at risk for injury, incomplete healing, and infection. Another useful assessment tool is the Brief Peripheral Neuropathy Screen used in several AIDS Clinical Trials Group protocols.43 With this tool, clinicians capture both subjective and objective findings by asking patients to rate the severity of their symptoms on a scale from 1 (mild) to 10 (most severe) and evaluating their vibration perception and deep tendon reflexes.24 Testing for reduced or absent Achilles tendon reflexes has a sensitivity of 84% and a specificity of 98% for DSP neuropathy in HIV.43 After assessing the patient's risk and documenting all foot exam findings, consider whether the patient would benefit from referral to a foot care specialist and schedule follow-up care.

Management. The Food and Drug Administration has not approved any therapies specifically for the treatment of HIV-associated DSP neuropathy. Current pharmacologic treatment is based on primary symptoms, with acetaminophen, nonsteroidal antiinflammatory drugs, antidepressants, anticonvulsants, topical agents, and opioids used as tolerated. Unfortunately, several drugs that are useful for other types of neuropathic pain—including the tricyclic antidepressant amitriptyline, topical lidocaine anesthetics, and the anticonvulsant pregabalin (Lyrica)—have been found to be ineffective for HIV-associated DSP neuropathy.44, 45

Symptom management also involves general lifestyle modifications, such as reducing cigarette smoking, attaining optimal nutrition, practicing meticulous foot care, and improving circulation through appropriate exercise. In 2010, the American Diabetes Association and the American College of Sports Medicine modified their positions to suggest that people with peripheral neuropathy who have no acute ulceration may participate in modest weight-bearing exercise.46 Moderate walking is unlikely to increase the risk of foot ulcers in people with peripheral neuropathy.
 
FOOT CARE EDUCATION

Nurses play a critical role in disseminating self-care information to patients. Since HIV-associated DSP neuropathy has many of the same signs and symptoms as diabetic and chemotherapy-induced neuropathies, foot care educational materials from such organizations as the American Diabetes Association, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Cancer Institute, and the American Cancer Society may be helpful to people with HIV. In studies of people with diabetes, foot care education improved patients’ foot care knowledge and practice in the short term.47

Daily foot hygiene. It's important to emphasize to patients that their feet need to be cleaned daily, using warm—not hot—water and a mild soap, and then towel dried thoroughly, particularly between the toes.48 Dry skin is a common foot problem. Advise patients with dry skin to moisturize the tops and bottoms of their feet with a thin coat of lotion—not a heavy cream or oil—and to avoid getting lotion between the toes. Nurses should counsel patients to inspect their feet every day for any cuts, cracks, blisters, redness, calluses, swelling, or dryness. Corns and calluses should be gently filed with an emery board or pumice stone after a bath or shower. Toenails should be cut once a week or as needed after washing, when they are soft. They should be cut to the shape of the toes and not too short. Patients who are unable to cut their nails should be referred to a podiatrist.

Footwear and fall prevention. Shoes should fit well and allow the toes to move. They should be wide enough to exert no pressure on the joints and long enough to allow 1 cm of space between the longest toe and the edge of the shoe when the patient is standing.49 Shoe material should be permeable because a warm, moist environment may harbor fungal organisms. Patients should shop for new shoes at the end of the day when their feet are larger from standing and walking; until new shoes are fully broken in, they should be worn only an hour a day. Before putting shoes on, patients should always check the insides to make sure the lining is smooth and there are no sharp edges that could injure their feet. Patients should always wear socks or stockings with shoes to prevent skin irritation and blisters. Remind patients that open-toed or thong sandals do not adequately protect the feet from injury. Reinforce the importance of wearing shoes at the beach.

Many older patients wear slippers indoors. Since DSP neuropathy may cause gait and balance problems, putting patients at risk for falls, teach patients about the importance of wearing slippers that fit properly and have slip-resistant soles.50 If a patient frequently stumbles, a walker or cane may provide needed support. To further protect against falls, advise patients to51, 52

* use night lights or keep a flashlight near the bed.

* roll up area rugs.

* remove any electric cords that could impede walking.

* install no-slip bath mats in the shower and tub.

Foot exercises. To promote lower limb circulation and prevent swelling, nurses should advise patients to elevate their feet when sitting, avoid crossing their legs, and perform simple foot exercises, such as wiggling the toes and moving ankles up and down, several times a day.

CONSIDER ALL RESOURCES

Although people with compromised immune systems and reduced sensory perception are clearly at elevated risk for foot infection, foot exams are often conducted only after a patient has established foot injuries. Advanced age further escalates the risks of HIV-associated foot problems owing to reduced peripheral nerve function, gait complications, and reduced mobility.27, 53

Within the diabetes community, efforts to educate patients on peripheral neuropathy and foot care have been intensive and should serve as lessons for providers who care for patients with HIV. Studies have shown that the efficacy of foot care education may depend on the type of education employed.54, 55 Nurses should take advantage of all available resources, including smartphone applications, which can set daily foot check reminders as well as provide instructional videos. By encouraging simple, preventive foot care education, nurses can promote health and overall well-being in patients at risk for HIV-associated DSP neuropathy, while reducing the potential for complications and related health care costs.

http://journals.lww.com/ajnonline/Fulltext/2013/12000/HIV_Peripheral_Neuropathy_and_Foot_Care.20.aspx

Neuropathy And HIV A Progress Report 2011 2012

 Today's long post via positivelite.com (see link below) was written by the moderator of this blog as a means of summing up the progress in neuropathy treatment over the past 18 months. There's a lot of information but it should give you an idea of what's going on in the research labs of the major  pharmaceutical companies and give you some hope that eventually, a treatment will emerge that will suit you as an individual with neuropathic problems.


Neuropathy and HIV: A Progress Report

Friday, 09 November 2012 Author // Dave R

Dave R writes...Neuropathy affects up to 40% of all people with HIV, yet the treatment has remained more or less the same for decades. Prescribing drugs meant for other diseases, has led to haphazard results; time for a change - but is it happening?
Couple the conditions neuropathy and HIV-infection together and in 2012, you have more people than ever who understand what you’re talking about. Growing older and surviving with HIV seems to mean the increase of long-term, age or HIV-related, side-effect conditions like neuropathy. To save time in relation to this article; much more information about the disease and its links to HIV can be found in other articles here, here and here.


It’s an infuriating and frustrating problem for both patients and doctors. Neuropathy is one of those diseases where the mainline, standard treatments seem to have remained static for the last thirty years or more. Occasionally, a different anticonvulsant is tried out, or a combination of antidepressant and anticonvulsant, analgesic, or opiate but this comes more from a feeling of hopefulness than conviction and good science on the part of doctors. In general, people who unfortunately end up with neuropathy from whatever cause (and there are over a hundred!) follow the same medication routes that have been used since the 60’s, until hopefully something works. It really is a sticking a wet finger in the wind sort of medical approach. The downside is that many people are never prescribed anything that really works for them and the symptoms can gradually worsen. In the end, the only pain-killing options are opioids, with all their attendant side effects and addiction potential. Little wonder that all involved tear their hair out with frustration. Medicine isn’t meant to be this way in the 21th Century; even HIV sees progression with its medications!

That’s probably why so many people turn to alternative therapies and supplements to try anything that might relieve the problems. In that sense, different supplements and therapies spring up every year like mushrooms in a field. Some end up being tested and approved and genuinely help people but many are pretty much worthless and a waste of money. That’s the biggest problem with neuropathy; it creates desperation and the need to clutch at straws. Yet the problem is largely unrecognised by the population at large, despite there being 20 million Americans alone who suffer from various forms of nerve damage. To be clear, only certain types of neuropathy can be reversed and even then, only when they are discovered very early in the disease – generally it’s something with you for the long haul.

Over the last decades, it has been a doom and gloom scenario for many people, as they work their way through drugs meant for other diseases in the hope that they will eventually get some relief from their neuropathic symptoms.

However, that very increase in numbers of people suffering serious nerve damage has sparked a wave of studies in the research world and glimmers of hope for sufferers. Unfortunately people living with HIV can’t take any of the credit; if it were just our little demographic, a cynic might suggest that new research wouldn’t be so forthcoming. Luckily for us (but not if you also have diabetes), it is the explosion in diabetes cases that is driving the need for effective treatments for neuropathy. The burgeoning disease of diabetes is the single largest cause of nerve damage, especially in the burger and sugar-guzzling West. That becomes a drain on health budgets and services; ergo a new enthusiasm in the research labs.

The outlook for neuropathy patients may not be quite as gloomy as it once was then and this article will bring you up to date with some of the more recent developments within the scientific and medical world. Be warned though, these will probably not result in ‘cures’ or even off-the-shelf medications in the very near future but do show that the pharmaceutical industry seems to be finally waking up to the fact that this is a huge problem across the entire spectrum of society. Significant progress seems to have been made even during the last year. As you know, drug companies are not known for their philanthropic motives but there’s a vast amount of money to be made as soon as effective treatments can be developed and that, plus pressure from health regulators to deal with diabetes, will unfortunately, probably be the driving force behind finding new treatments. That said; do we care how they get there? Not if we have neuropathy we don’t! Whatever the motives, we’re going to love the pharmaceutical company that brings us genuine relief from nerve damage.
Recent Developments in Research

The following are some of the many recent developments in understanding of how, what and why nerves are damaged and what can be done to alleviate the results.

First, a step backwards but an important one for many people currently being prescribed the anticonvulsant Lyrica (pregabalin) for neuropathy. For those who haven’t already heard, in May 2012 Lyrica (Pregabalin) was dropped as a treatment for diabetic and HIV-related neuropathy by none other than its makers, Pfizer. It proved to be ineffectual in treating neuropathy from those causes. Despite this, doctors all over the world are still prescribing it because they either haven’t heard, or because it’s on the standard list, or they have always prescribed it and have a number of patients for whom it seems to have worked. The fact is that the majority of people have found no improvement from taking Lyrica (pregabalin) and what’s more have suffered more from the side effects than from the neuropathy itself. It may be worth discussing this with your specialist if that’s the case for you. For Pfizer to withdraw support for their own drug is hugely significant – no drug company cuts the throat of its own cash cow for no reason!

By far the largest area of research is at molecular and cellular level which may leave most people scratching their heads and reluctant to read on. However, scientists in both universities and the pharmaceutical company research departments seem to have recently invested a great deal more time in looking at nerve cells, why they are damaged and what processes both chemical and physical cause so much pain and discomfort for neuropathy patients. Of course, this sort of research has undoubtedly been going on for years but with discouraging results, (otherwise new treatments would have been available long before now). The technology must also have improved to the point where more detailed and specific research is now possible. Published scientific findings also stimulate both new research and competition, so exciting results in one university or research lab tend to encourage others to top them with results of their own. More money for research may also be available, as political decisions outside the pharmaceutical industry influence progress. Administrations everywhere are realising the huge costs associated with ‘life-style’ illnesses like, diabetes, cancer, HIV and others. They also realise that continuing to pour money into paying for ineffective treatments with side effects just prolongs the process and increases costs exponentially. The pharmaceutical companies may finally be facing pressure from politicians but they are also beginning to realise the vast profits to be made from finding the ‘mother lode’ of nerve damage treatments. They can no longer really justify making profits from and using up reserves of drugs used for other medical conditions, when they have such a hit and miss effect on neuropathy patients. Sheer numbers and potential profits, then, are driving the search for new drug treatments.

So is it possible to describe some of the developments in molecular and cellular research for nerve damage? I’ll give it a go and have to confess my own understanding is about as shallow as most people’s but we need to have an idea of what sort of treatments are going to affect our futures with this disease. If nothing else, it helps us to understand exactly how complex the whole problem is.

The first is new research that has identified precisely which cells and which sub-sets of cells, are responsible for long-term nerve pain. See an explanation here.

Then studies have identified the cells (Schwann cells) which protect the myelin sheath which is the insulation layer around nerves (to give you an idea, a myelin sheath is like the plastic around electricity wires – you get a short circuit if that is damaged too). More information about this research can be found here.

Further research has identified the importance of something called metabolomics. This looks at why nerve pain persists for so long and why many medications have no effect. The clue lies in a by product of cellular membranes called DMS which seems to be present in large amounts in the spinal cords of lab rats and mice with neuropathy. They are working on finding ways of inhibiting this DMS and thus relieving long-term pain. More information here.

Similarly, American researchers have discovered a group of drug molecules which are found naturally in the body and stabilise other molecules, in order to block neuropathic pain. The idea is that these selective molecules inhibit a key enzyme called soluble epoxide hydrolase. Blocking this enzyme successfully blocks pain sensations. This then has implications for developing new drug treatments which will work much better on neuropathic symptoms. The problem is that the research is still in a very early stage. Read more here.

Another research study aims to block nerve pain signals by using glycene. Glycene is an amino acid which is known as an inhibitory neurotransmitter. It works at the junction between two nerves, known as the synapse and halts the transmission of pain signals along those nerves to the brain. However, glycene quickly dissipates in these places and some have recommended taking supplements to encourage the body to create more naturally. This study questions the efficiency of that but points out that glycene is one of the very promising natural products of the body which needs and is getting much more research. More information here.

Yet another research study has discovered that a certain protein (LRP4) has to be present on the surface of both muscles and in the brain in order to regulate muscle function. If this isn’t the case, several conditions including neuropathy can occur. Many neuropathy patients discover that their muscles stop working efficiently and lose strength after time – the lack of this protein LRP4 in both muscle cells and neurons leads to communication breakdown, which as we all know leads to the numbness, tingling and pain which often appear with nerve damage. Finding a way to either maintain protein levels or introducing it externally may well help reduce the problem. More information here.

Another project has looked into how the brain stores memories of pain and why for instance, phantom limb pain occurs (when a limb is lost, people still feel the pain as if it’s still there). Again, it concerns a type of protein (PKMzeta) which builds and maintains memory by strengthening the connections between neurons. Scientists think that if they can block the activity of PKMzeta, they can reduce the hypersensitivity that causes nerve pain and they’re well on their way to finding something that will do just that. Again, a work in progress we have to say but the future looks a little more hopeful. Read more here.

Finally in this group of studies, the possibilities of nerve transplantation are being explored, in cases where nerves are damaged. This means basically transplanting immature neurons in the hope that they will grow into full nerve cells. During the studies small fractions of the transplanted cells survived and matured into functioning neurons. The cells then integrated into the nerve circuitry of the spinal cord, forming synapses and signalling pathways with neighbouring neurons. Most importantly, as a result, pain hypersensitivity associated with nerve injury was almost completely eliminated. Whether health authorities will be able to cope with the expense of this sort of transplant treatment is the question but there’s little doubt, it sounds promising! More information here.

You can see from these few examples that many people and research labs are busy working at the most basic level of nerve behaviour to find where, why and how, molecular and cellular activity cause such unpleasant neuropathic symptoms. Genetic research is another fast-growing sector, largely due to the huge advancements in techniques in that area and eventually, altered or modified DNA may provide permanent answers. It is slow work though and we have to hope that sooner rather than later a significant breakthrough will be made. Hoping that just one of the studies above may lead to real treatment progress, gives room for optimism.
Researching Nature

Research is not only being done at microscopic levels within the body but studies are also being done in nature to see if there is anything in the animal and plant kingdoms which may help. This has produced some strange studies and conclusions.
A certain sea-snail saliva for instance could be a replacement for morphine in the future. Read more here.
Taiwanese scientists have discovered a compound derived from certain corals called Capnellene. This may also work on certain cells (microglia) and significantly reduce neuropathic pain. More information here.
Scorpion, spider and snake venoms may also provide answers to controlling nerve pain. These venoms work on the sodium channels in the nervous systems of mammals, so it seems logical that controlled doses may help with neuropathic symptoms. Read more here.
Turmeric (also known as Curcumin, Curcuma) which is used widely in cooking, is one of the new buzz words for helping with all sorts of problems including neuropathic pain. Every now and then, a natural remedy emerges that catches on in the market; sometimes with merit and sometimes not. However, one of the most promising is Turmeric or Curcumin, a root used widely in Asian cuisine, generally in powder form. It’s cheap and maybe worth a try – some people swear by it but do your own research. More information here.

Of course the best known natural remedy used to help with neuropathic problems is cannabis. The hysterical reactions to cannabis for medical purposes are much more to do with politics and ‘the war on drugs’ than the medical benefits it can undoubtedly bring for many people. It’s one of the very few recognised effective remedies for neuropathic pain but a) you have to be aware of the laws in your area, b) you have to be able to smoke it (with all its associated lung dangers) and c) you have to be able to cope with getting high (mildly or otherwise). For those reasons many people can’t take advantage of cannabinoids. However, there has been a new synthetic version of THC (the principle working element of cannabis) created by the University of Calgary and this could prove to be a godsend for many neuropathy sufferers because smoking will be removed from the equation. It is far more likely to be accepted by law agencies because it can then be issued on prescription. However, like most developments, we’re not there yet. (Read more here.
Other approaches

There are many more studies and investigations of potential natural remedies, from many different natural sources taking place. If only a handful end up being successful and effective and available to our doctors, or on the shelves of our health food shops, it could relieve suffering for millions.

It seems that no stone is being left unturned in the search for answers and that includes looking at other cultures and other medical practices. Acupuncture and acupressure have been tried by many neuropathy patients over the years, with varying levels of success. Like everything else at the moment, it works for some but not for others. However, new research has discovered that much longer-lasting effects can be achieved by so-called PAP injections (prostatic acid phosphatase) using the same pressure points used for centuries in acupuncture. This so-called PAPupuncture therapy has been proved (in the lab) to extend pain relief much further than with normal acupuncture methods and may well be a useful therapy in the future, for those who don’t wish to increase their drug consumption. Read more here.

Finally in this section, it may seem that the world is turned on its head but a modified version of the herpes virus is thought to theoretically work on peripheral nerves, so that pain can be directly reduced in those areas. A scary thought perhaps, if you’re to be injected with herpes but perhaps logical if you think that Shingles is also a form of neuropathy and is caused by a herpes virus. Anyone suffering from Shingles, knows what nerve pain can do! More information here.

Lastly, apart from the searches for new medications and treatments, which are very difficult for the layman to understand, scientists are also trying to develop better versions of current drug treatments. We know about the random success/failure rate of antidepressants and anticonvulsants and it is likely that there isn’t much progress to be made in those drug areas. We also know about the last resorts in the opioid family. Effective pain killers but often strongly addictive and loaded with side effects, they are unfortunately a question of necessity for many neuropathy patients.

Scientists are discovering that opioids are a group of drugs with more possibilities and their effectiveness is probably more easily adapted and manipulated. Consequently, new opioids and members of the opioid/morphine family are coming on to the market. Tapentadol,(Nucynta in the USA and Palexia in Europe) for instance, is newly approved in the States and can be equated to Tramadol but works slightly differently, more effectively and with less side effects. It will be a welcome alternative for many people. Read more here.

Researchers are also looking for ways to prolong the pain-killing effects of morphines and opioids, thus reducing the need for higher doses and reducing addiction dangers. They have found that Resveratrol, (naturally found in red wine) can preserve the effects of morphine in rats - most importantly, in rats that have developed morphine tolerance. In humans, morphine tolerance creates a need for higher doses to achieve the same effect so discovering something that delays tolerance, or maintains the pain killing effects, is clearly of great value. See more here.
Conclusion

If you’ve got this far, you’re probably reeling from information-overload but the intention is to reassure you that serious efforts are being made to find solutions for both nerve damage and the uncomfortable results of that for millions of people. Eventually, a few will make it through the rigorous processes and end up as viable options for our doctors to prescribe. Unfortunately, it takes time and that’s difficult to swallow for a patient in extreme pain or discomfort. You’re already on drugs for your neuropathy; they may be working or not, or just partly. All you want is something to take the problem away and preferably a one-drug-cures-all type of treatment. The truth is that that’s not going to happen in the very near future but it will eventually happen. Finally, health authorities and pharmaceutical companies are getting their acts together and working for us instead of palming us off with dangerous drugs meant for other diseases.

Money will play a part in the speed of progress and research finance is often the first to go in times of financial crisis, along with the willingness of health authorities and insurance companies to pay for expensive new drugs but the picture is brighter than ten years ago. All concerned are realising that neuropathic pain is a far greater problem than they ever imagined and the increase of the diseases that cause it (along with people living longer) is only going to make that bigger. Something has to be done to reduce the costs of long term treatment and that means finding things that genuinely work. Lab rats and mice may view this with horror but for many people with neuropathy, it just can’t come soon enough!

http://www.positivelite.com/component/zoo/item/neuropathy-and-hiv-a-progress-report

DYNAMIC MOTION OF HIV AS IT READIES AN ATTACK

Researchers at Weill Cornell Medical College have developed technologies that allow investigators, for the first time, to watch what they call the "dance" of HIV proteins on the virus' surface, which may contribute to how it infects human immune cells. Their discovery is described in the Oct. 8 issue of Science, and is also a part of a study published the same day in Nature.

The new technology platform opens new possibilities for devising an approach to prevent HIV infection, says Dr. Scott Blanchard, an associate professor of physiology and biophysics at Weill Cornell, and one of three co-lead authors on the Sciencestudy. He is also an author on the Nature paper that describes a three-dimensional structure of one of the shapes, or conformations of the HIV protein.

"Making the movements of HIV visible so that we can follow, in real time, how surface proteins on the virus behave will hopefully tell us what we need to know to prevent fusion with human cells -- if you can prevent viral entry of HIV into immune cells, you have won," says Dr. Blanchard, who is also associate director of Weill Cornell's chemical biology program.

"What we have shown in the Science study is that we now have the means to obtain real-time images of processes happening on the surface of intact HIV particles, which we now plan to use to screen the impact of drugs and antibodies that can shut it down," he says.

"We desperately need solutions to prevent HIV infection, which, to date, has infected or killed more than 70 million people worldwide," Dr. Blanchard says. If this technology proves useful in HIV management, it could potentially be used to decode infection processes for other viruses, he says.

Using Light to Watch HIV Dance

In the Science study, Dr. Blanchard worked with Dr. Walther Mothes, a HIV specialist at the Yale University School of Medicine, and with Dr. James Munro, who was Dr. Blanchard's first graduate student and who is now an assistant professor at Tufts University School of Medicine. Drs. Mothes and Munro are the two other co-lead investigators.

Dr. Blanchard adapted an imaging technique that uses fluorescence to measure distance on molecular scale -- single-molecule fluorescence resonance energy transfer (smFRET) imaging -- to study viral particles. His group developed fluorescent molecules (fluorophores) -- which he dubs "beacons" -- and the team inserted them into the virus's outer covering, known as the envelope. With two of these special beacons in place, smFRET imaging can be used to visualize how the molecules move over time, when the virus proteins change conformation. The approach provides a measure of distances, on the order of a billionth of an inch, between two beacons glowing in different colors, and this can be used to detect shape shifting as it occurs and the attached beacons move.

The team used the technology to study motions of proteins on the surface of the HIV virus (called envelope proteins) that are key to the virus's ability to infect human immune cells carrying CD4 receptor proteins. (CD4 receptor proteins help HIV bind to a cell.) The envelope consists of three gp120 and gp41 proteins positioned close together, and referred to as "trimers," that open up like a flower in the presence of CD4, exposing the gp41 subunit that is essential for subsequent aspects of the mechanism that causes infection.

"There are 10-20 such envelope trimers on the surface of each HIV particle, and they mutate rapidly, thereby evading typical immune responses. This is why it is so difficult for humans to mount an effective immune response and why it is challenging for researchers to develop vaccines targeting the HIV envelope proteins," Dr. Blanchard says. The researchers were able to study proteins from two different strains of HIV, which contained beacons that did not alter the biology of the particles.

Then they watched.

They saw that the gp120 proteins' virus particles changed shape constantly and that the timing and nature of their movements were both similar and distinct. "This answered the first big question of how opening of the envelope trimer is triggered," Dr. Blanchard says. "Many scientists believe that the particles remain in one conformation until they come across a CD4-positive cell. But we saw that the proteins dance when no CD4 was present -- they change shape all the time."

The researchers were then able to watch how the viruses responded when synthetic CD4 was introduced. They also saw that antibodies known to exhibit some effectiveness acted to prevent gp120 from opening, and that these effects correlated with a decrease in the virus' ability to infect cells. Similar things happened when they introduced a small molecule now under development to prevent HIV infection.

"The practical outcome from this technology is that we can begin to understand how the biological system moves. So far we have detected three different conformations of the envelope trimer. We are working now to improve the technology to achieve the imaging precision we need to make broadly effective therapies," Blanchard says.

Technologies Work Hand in Hand

The Nature study, led by researchers at the National Institute of Allergy and Infectious Diseases, used X-ray crystallography to capture a three-dimensional structure of one of the conformations revealed in the Science paper. The protein constructs used in this investigation were originally developed by a team of researchers headed by Dr. John Moore, professor of microbiology and immunology at Weill Cornell.

"The antibodies used in the crystallography study are ones that we observed to stop the dance of the HIV envelope proteins, pushing the trimer assembly into a quiescent, ground state," Dr. Blanchard says.

"This concrete, atomic resolution picture of what the pre-fusion machinery looks like and where these antibodies bind provides an important step forward to understanding HIV's biology," he says.

Dr. Blanchard believes both techniques -- smFRET and X-ray crystallography -- can work hand in hand to help scientists describe the functions of molecules from the perspective motion, including the other two distinct conformations identified in the smFRET study.

"The approach is really a breakthrough for science because most research is done in a test tube where billions of molecules are present, all behaving independently. It is very difficult to extract direct information about these types of movements from indirect observations," such as those that don't use imaging technology, he says. "The single-molecule approach allows practical, interpretable, real-time information to be obtained about molecular processes in complex biological systems."