Today's post from salonpas.us (see link below) is not from the silly season of New Age platitudes designed to make you feel better about yourself while doing little to relieve your condition - it's better balanced than that. It's that word 'holistic' which turns so many readers off from the beginning but holistic simply means looking at the whole patient's health rather than specifically neuropathy. In that sense, it offers some useful suggestions regarding taking care of your whole self rather than just for instance, the pain areas in your feet or hands. The article is really an advertisement for their products but because this blog avoids advertisers, the live links have been removed (you can see them by surfing to the original site page). However, if there is information that is of value to all neuropathy patients, then we will happily publish that and that's the case here. It makes sense really; neuropathy affects so many areas of your life and your body - taking a global view of your health is essential. Remember: the word diabetic in terms of neuropathy is not exclusive to diabetes patients but you knew that didn't you?
January 2016
About 60-70% of people with diabetes have some form of neuropathy, which is nerve damage. What are the symptoms of diabetic neuropathy and best holistic treatments? Salonpas sat down with Dr. Robert Pomahac, a board certified chiropractic physician and certified wellness practitioner at MaxHealth and Dave Endres, licensed physical therapist and co-founder of the SPEAR Physical Therapy Center in New York City, to discuss treatment and lifestyle options to reduce diabetic neuropathic pain:
What is neuropathy and what are the signs and symptoms?
“Neuropathy means nerve disease or damage,” says Dr. Pomahac. “Symptoms can range from numbness or tingling to pricking sensation or muscle weakness. Severe symptoms may include burning pain, muscle wasting, paralysis, or organ or gland dysfunction. Neuropathy is a progressive condition, meaning it tends to get worse with time. If left untreated for too long, the nerve damage can reach a point where there is simply nothing that can be done. This is why early detection and treatment of peripheral neuropathy is critical to getting the best results.
One of the most dangerous aspects of peripheral neuropathy is the effect that it can have on balance. If the nerves in the feet are damaged and not sending good communication to the brain this results in alterations in balance. Many patients with neuropathy report that they feel unsteady on their feet, or have a hard time walking in a straight line.”
What tests can someone take to learn if they have neuropathy?
“Since the symptoms of peripheral neuropathy are highly variable, a thorough neurological examination is required to figure out the cause of the symptoms,” says Dr. Pomahac. “A complete medical history discussing the symptoms, work environment, social hobbies, exposure to environmental toxins, use of alcohol and or drugs, infectious diseases and family history of neurological diseases are vitally important in helping properly diagnose and treat effectively.
Specific tests to help diagnose if you are suffering with peripheral neuropathy include nerve conduction velocity (NCV), MRI and even an electromyography (EMG), and superficial pain sensation testing.”
Why do 60-70% of people with diabetes also suffer from neuropathy?
“Damage to delicate nerve fibers can occur when you have prolonged exposure to high blood sugar,” says Dr. Pomahac. “High blood sugar interferes with the ability of the nerves to transmit their signals and it also weakens the walls of the small blood vessel that supply the nerves with oxygen and nutrients.”
Physical trauma, infection, repetitive injury, metabolic problems and exposure to toxins can lead to neuropathy. What can someone do to avoid having this condition?
“Neuropathy may be as a result of spinal pressure in the neck or lower back,” says Dr. Pomahac. “Having a complete diagnostic evaluation of the spinal alignment through an X-Ray analysis to determine structural stress of disc pressure on the nerves causing neuropathy is a key part of prevention. Working on standing and sitting posture and understanding body neutral helps to reduce the overall stress on your body and may help with nerve pressure. Another treatment that may be beneficial is decompression therapy to help remove disc pressure. If you are having peripheral neuropathy a treatment including light laser to helps to create vasodilation, or widening of the blood vessels, and vibrational therapy to stimulate new capillary and nerve regeneration. Finally, eliminating inflammation-based foods like sugar, soy, dairy, gluten and processed foods is recommended.”
Are there any recommended prescription or OTC drugs for neuropathy?
“We work closely with a patient’s doctor to ensure that their pain management is safety managed through drug therapy when necessary,” says Endres. “However, if there is a choice between oral or topical pain therapies, we encourage the transdermal route every time. OTC transdermal pain therapy, ensures a control-released delivery of pain medication.”
“I think the combination of eastern and western medicine supplements is the best option for people suffering with peripheral neuropathy,” says Dr. Pomahac. “Some natural herbs and supplements you should consider after taking with your physician include; alpha lipoic acid, which is a powerful antioxidant used to treat nerve damage, N-Acetyl Cysteine helps detoxify the body and Magnesium soothes the nervous system. Vitamin B deficiency has shown to cause neuropathic pain. Cayenne used as massage oil is beneficial Skullcap and evening primrose oil both help with the nervous system as a whole.”
Are there any recommended exercises for neuropathy patients?
“Physical therapy is used to alleviate many sources of pain, including neuropathic pain, muscle cramps, osteoarthritis, fibromyalgia, chronic headaches, rheumatoid arthritis, hamstring pain, back, shoulder and neck pain, just to name a few,” says Dave Endres.
“Exercising 30 minutes a day at least three or four days a week aids chronic pain management by increasing endurance, muscle strength, and flexibility in the muscles and joints,” says Endres.
“Consider a vibrational plate while performing resistance training,” says Dr. Pomahac “Aqua therapy with resistance, yoga, tai chi, swimming are all beneficial Using cardio equipment like a recumbent-bike removes balance issues associated with lack of extremity sensation. Weight loss and improvement in lean muscle will benefit any person and help take pressure of your neurological system.”
How can you control the symptoms of neuropathy?
“The key is prevention,” says Dr. Pomahac. “Proper foot care is essential which includes cleaning and inspecting your feet daily. Wear comfortable, supportive shoes that fit your feet. Wear socks with padding on the pressure points of your feet. Cut your toenails straight across or get your foot doctor to properly trim them regularly. Regular warm baths provide some relief from mild nerve pain.”
For more information on neuropathy, visit The Neuropathy Association, the Neuropathy Action Foundation and the Foundation for Peripheral Neuropathy.
http://salonpas.us/blog/holistic-diabetic-neuropathy-treatments/
Today's post from relief.news (see link below) talks about how people living with HIV have lived with the disease and the pain that often goes with it - sometimes better and with more resilience than people without HIV in their lives. Up to 40% of people living with HIV suffer from neuropathy. Nobody's has got to the bottom of why this happens. It's assumed to be a side effect of long-term HIV medication, or the virus itself attacking the immune system, or a combination of both with other factors thrown in. Considering the stigma that is still attached to HIV, it makes a pleasant change to read an article that shows that HIV patients can actually live with the pain far better than the rest of the population faced with the same pain levels. An interesting article...worth a read.
The Role of Resilience and Physical Activity in HIV-Related Pain By Relief Staff December 13, 2016
How is HIV-related pain different from other types of chronic pain?
People living with HIV experience pain similar to people with other chronic conditions. For example, people with HIV can have similar nerve pain in the feet and legs as diabetics. The significance of our study is that HIV-positive patients react to their pain differently.
Many people with moderate to severe chronic pain find it difficult to move around. But we found that, in contrast, HIV-positive people who had chronic pain were still active.
There were two parts to our study: we measured activity and resilience (or a person’s ability to cope with adversity). We wanted to see if HIV-positive people with pain moved less than those without pain and if resilience affected how much they moved. We also wanted to know if resilience affected how much pain they felt.
We measured activity by getting participants to wear movement detectors over two weeks. It helped us understand how much patients with chronic pain moved and how much time they spent being active each day. The overarching finding was that activity levels did not drop as pain increased.
In previous studies, women who suffered from rheumatoid arthritis spent large parts of each day not moving. And similarly, women who experienced really bad period pain moved much less when they were menstruating.
But people living with HIV and chronic pain did not stop their usual activities, despite the pain they experienced.
To measure resilience we used a questionnaire developed by pain researchers in the U.S. Researchers from Europe have used this questionnaire to assess resilience in patients experiencing chronic spinal pain. They found that people who were more resilient coped better with chronic pain and were more active.
Our assumption was that the more resilient patients were, the more active they would be. This assumption proved to be incorrect. Resilience made no difference to activity levels. We also assumed that resilience would lead to participants experiencing less pain. But that wasn’t the case either. Patients who were more resilient did not have less pain.
What type of pain do people living with HIV experience? How common is it?
One in every two people with HIV experience pain. This includes headaches, chest pain, back pain or frequently peripheral nerve pain in their feet and hands.
The pain can be moderate to severe and can be caused by the immune system’s response to the virus or can co-occur with it. The pain does not tend to go away when patients go onto antiretroviral drugs. Some drugs have been shown to inadvertently induce pain. While the pain can be short-lived, it can also become chronic.
So what factors did play a role in activity levels and why?
There were two reasons why HIV-positive people with pain may have continued to be active: financial stresses and stigma.
We found that younger participants, unemployed participants and those that worried most about getting food were the ones who were more active. It seems they relegated their pain to a lower priority.
Our study also showed that stigma often stopped people from talking about their pain and may have motivated them to keep active.
We asked the participants with pain who they spoke to about their pain. Nearly half of the patients had not told their closest friends and some had not disclosed this to their family. They said they feared that talking about their pain might reveal their HIV status.
Why are these findings important and what’s next?
The HIV-positive patients who were more resilient were more satisifed with their health.
HIV-related pain is really difficult to treat. Improving resilience, for example, with psychological treatments, may be one way of improving patients’ satisfaction with their health even if their pain stays the same.
With other kinds of chronic pain, people who keep active do better. But sometimes, pushing through pain can actually make pain intensity and disability worse. In this study we looked at how pain affects activity in HIV. Now we need to look at how activity affects pain.
We know that for patients with other kinds of pain, social support is really important to help them cope. HIV-positive patients may go without social support if they conceal their pain. We need to understand how they cope instead.
The impact of HIV stigma on pain also needs to be investigated.Editor’s Note: Antonia Wadley, PhD, is a postdoctoral fellow in the School of Physiology, Faculty of Health Sciences, at the University of the Witwatersrand in South Africa. Wadley is originally a physiotherapist from the UK but now researches HIV-related pain. Wadley and colleagues published a recent study on the role of resilience and activity in HIV-related pain. The interview below, where Wadley describes her recent work, was originally published in The Conversation Africa, and is reprinted here with Wadley’s permission. Also see a related YouTube video on the study here.
http://relief.news/the-role-of-resilience-and-activity-in-hiv-related-pain/
Today's post from vector.childrenshospital.org (see link below) is already a year old and we can expect that further advances will have been made but it introduces the idea of genetically creating nociceptors (pain-sensing nerve cells) in a dish, in a lab. The idea being that, pain-killing drugs can be tested safely without needing animal or human models. Furthermore, these nociceptors will be created so that there are far less variables than in animal test subjects, thus creating more certainty, more speed and quicker development of future drugs. This sort of stem cell research is a huge breakthrough and chronic nerve pain patients will certainly benefit from new medications in the years to come because the research is so much easier and much more specific. It's a short article and easy to follow - worth a read.
Posted on December 12, 2014 by Nancy Fliesler
Chronic pain, affecting tens of millions of Americans alone, is debilitating and demoralizing. It has many causes, and in the worst cases, people become “hypersensitized”—their nervous systems fire off pain signals in response to very minor triggers.
There are no good medications to calm these signals, in part because the subjectivity of pain makes it difficult to study, and in part because there haven’t been good research models. Drugs have been tested in animal models and “off the shelf” cell lines, some of them engineered to carry target molecules (such as the ion channels that trigger pain signals). Drug candidates emerging from these studies initially looked promising but haven’t panned out in clinical testing.
“These models don’t tell you what the drug is doing to the whole functioning neuron,” says Elizabeth Buttermore, PhD, a postdoctoral fellow in the F.M. Kirby Neurobiology Center at Boston Children’s Hospital. “They haven’t been holding up.”
Last month in Nature Neuroscience, Buttermore coauthored a report with Brian Wainger, MD, of Boston Children’s and Massachusetts General Hospital, describing a new model that appears to capture pain physiology in a dish, using skin cells as their raw material. Their model, also a technical breakthrough in stem cell research, offers new opportunities to understand how pain is produced and to discover new analgesics.
A nimbler way to make neurons
Labs all over the world are beginning to reprogram skin cells into cells resembling embryonic stem cells, known as induced pluripotent stem (iPS) cells, and transforming those, in turn, to their cell type of choice. But Buttermore, Wainger and colleagues found that they were able to bypass the somewhat cumbersome step of creating iPS cells.
By adding just five signals (namely, transcription factors) to skin cells from mice and from patients with an inherited pain disorder, they were able to create nociceptors—specialized pain-sensing neurons. Two of these signals hadn’t been known before and were found by examining mature nociceptors from mice.
In tests, the lab-created mouse nociceptors closely resembled “natural” neurons. They functioned, responded to different pain triggers and became hypersensitized to pain just like their real-world counterparts. The lab-created human nociceptors still have some hoops to jump through, but by early measures, they appear to “beautifully model” patients’ neuropathies and pain hypersensitivities, says Clifford Woolf, MB, BCh, PhD, senior investigator on the project and director of the Kirby Center.
The nociceptor model is already revealing new aspects of pain physiology and could ultimately provide a much more realistic platform for testing new drugs. Woolf, who also co-leads the Harvard Stem Cell Institute’s Nervous System Diseases Program has already found this to be true for amyotrophic lateral sclerosis (ALS).
The nociceptor project’s success was a long time in coming. The team had first tried to make nociceptors from embryonic stem cells. “We spent three years trying to recapitulate the developmental steps involved, and it turned out to be a total bust,” said Woolf.
But he refused to pull the plug, and the approach that finally worked turns out to be the most expedient and the most clinically relevant: Skin cells can be collected directly from patients, making it easier to model their different kinds of chronic pain—neuropathies caused by genetic mutations, diabetes or even chemotherapy, which can sensitize patients to pain.
“We’re trying to get to clinical trials with more success,” says Buttermore. “Hopefully, we’ll avoid drugs that don’t work.”
http://vector.childrenshospital.org/2014/12/modeling-pain-in-a-dish-nociceptors-made-from-skin-recreate-pain-physiology/
Today's post from podiatrytoday.com (see link below) Looks at the advantages of combining topical analgesics to provide better relief for neuropathic pain patients than the range of pills currently prescribed. Side effects and effects on the stomach, liver and kidneys, plus psychological effects mean that taking current pill choices can lead to serious complaints that have nothing to do with the original problem (nerve damage). They may reduce symptoms but are often producing unwelcome symptoms of their own. This complex article (takes some reading!) suggests that combinations of drugs applied topically (through the skin, as creams) can target problem areas more effectively and reduce potential side effects by not travelling through the digestive system. It's an interesting (though not new) theory that deserves much more attention than it currently gets. For a start, although topical versions of many neuropathic treatment drugs are currently available, they are rarely combined to produce optimum effect. New products will need to emerge and the question is whether the drug companies are prepared to make the necessary investments when they already have pill versions of the same components. Worth a read, even if you don't understand everything fully.
Monday, 02/23/15 | Issue Number: Volume 28 - Issue 3 - March 2015
Author(s): Allen Jacobs, DPM, FACFAS
Topical compounded medications may play a key role in the armamentarium of treatments for diabetic neuropathy, particularly patients who have multiple comorbidities and polypharmacy issues. Accordingly, this author demonstrates how compounding can optimize drug concentration at the site of pain with a lower risk of adverse sequelae.
The treatment of diabetic neuropathy includes efforts to correct the underlying metabolic disorder as well as addressing symptomatology associated with diabetic neuropathy.
Neuropathy secondary to diabetes is likely the most common peripheral neuropathy that podiatrists treat. The pathologic basis for diabetic neuropathy remains unclear and there are no proven therapies that studies have demonstrated to universally interdict or reverse the progression of diabetic neuropathy. However, some therapies are helpful at reducing symptomatology secondary to diabetic sensory neuropathy, preventing further nerve degeneration and possibly enhancing the regrowth of nerves.1
Diabetic neuropathy typically begins as a small fiber neuropathy affecting the small unmyelinated or thinly myelinated nerve fibers that subserve pain, temperature perception, heart rate, blood pressure, sweat function and gastrointestinal function.2
The signs and symptoms of diabetic neuropathy include manifestations of sensory, motor and autonomic dysfunction.3 These symptoms may include numbness, dysesthesia, paresthesia or allodynia. Decreased thermal sensation and vasomotor dysfunction are also early manifestations of diabetic neuropathy. Edema, imbalance and ulceration are known complications of diabetic neuropathy.
Motor neuropathy may be characterized by an intrinsic minus foot with atrophy of the normal intrinsic muscles, resulting in hammertoes and prolapse of metatarsal heads. Symptoms such as cramping, aching, and decreased knee and ankle reflexes may also occur. Autonomic neuropathy may be associated with vascular calcification, skin xerosis with sudomotor dysfunction, neuropathic edema, resting tachycardia or Charcot joint disease.3
A variety of metabolic disorders occur in patients with diabetic neuropathy. This includes sorbitol accumulation, increased fructose, decreased myo-inositol, glycation end products, the generation of reactive oxygen species, decreased nitric oxide production, activated protein kinase C, increased cytokine activity and decreased neural growth factors.
Pertinent Considerations In The Treatment Of Diabetic Neuropathy
The treatment options for diabetic neuropathy include the management of serum glucose, which will delay the onset of the condition and slow the progression of neuropathy. A variety of supplements such as L-methylfolate/methylcobalamin/pyridoxal-5’ phosphate (Metanx, Pamlab), alpha lipoic acid, carnitine, benfotiamine and others have been effective in the stabilization of symptomatology associated with diabetic sensory neuropathy.4 In addition, pain management for dysesthesia and paresthesia may be required.
The use of antinociceptive medications may be helpful in the treatment of painful paresthesia and dysesthesia in the patient with diabetes. However, such medications do not assist in reversal of the underlying metabolic deficits responsible for the etiology. Similarly antinociceptive medications are not helpful in the treatment of motor neuropathy or autonomic neuropathy, in the patient with diabetes.
The reversal of the actual metabolic defects and remittive therapy for neuropathy generally require good control of diabetes as well as supplements or nutritional therapy. Additionally, decompression surgery may be of benefit in decreasing the progression of, or reversing, symptomatic and non-symptomatic diabetic neuropathy.5
The majority of patients with diabetic neuropathy demonstrate sensory anesthesia, motor dysfunction and autonomic dysfunction, and not paresthesia or dysesthesia. However, between 20 and 30 percent of patients with diabetes have disturbances with paresthesia and dysesthesia, requiring pain management.6-8
When it comes to painful neuropathy, clinicians initially rule out non-diabetic causes of neuropathy and look to stabilize glycemic control.9 The treatment of symptomatic diabetic neuropathy typically involves the use of tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, anticonvulsant medications or opioid or opioid-like medications.10 Unfortunately, concern about potential adverse reactions with these oral medications prevents their use in many patients. Tricyclic antidepressants, for example, may be associated with weight gain, edema, anticholinergic side effects, neuropsychiatric side effects and cardiac conduction abnormalities.11 Similarly, antidepressants may be associated with a significant risk of incoordination, falls and other neuropsychiatric side effects.12
Since these oral medications for the treatment diabetic neuropathy have a significant side effect profile, many podiatric physicians generally do not employ them as they are understandably reluctant to utilize such medications to provide relief from painful paresthesia and dysesthesia.
Comparing Oral Medications To Topical Compounds And Their Mechanisms Of Action For Diabetic Neuropathy
Numerous physiologic mechanisms transmit pain and we can generally reduce these mechanisms to transduction or transmission functions. A variety of receptors participate in either the initiation of pain conduction or the blockade of pain transmission. Typically, oral medications for the treatment of painful diabetic neuropathy act at one receptor site. This may explain why some patients do well, for example, with an anticonvulsant, and do not respond to other agents such as antidepressants. It is difficult to predict in each individual patient which transmission site or sites are most important for the degeneration of diabetic neuropathic pain. Therefore, the prescription of medications is somewhat “hit or miss.”
As an example, antidepressants have activity in the generation of peripheral analgesia by activation of adenosine a1 receptors while inhibiting noradrenaline release as well as the uptake of 5-hydroxytryptamine. Topical agents such as capsaicin have long been known to produce analgesia by activation of vanilloid receptor-1, blockade of substance P and release of calcitonin gene-related peptide.13 Local anesthetics may act on voltage-gated calcium-2 channels and reduce ectopic repetitive firing of primary nerve afferents following injury.
Topically applied compounded medications provide relief of diabetic paresthesia and dysesthesia via multiple mechanisms of action. Since they affect multiple receptor sites and can simultaneously inhibit the production of substances that initiate pain, topical compounded medications provide an increased ability to resolve pain.
Topical compounded medications can simultaneously provide an anti-inflammatory medication, a tricyclic antidepressant or an anticonvulsant. They offer the opportunity to provide direct anti-inflammatory and antinociceptive relief with marked reduction in the potential adverse reactions associated with oral medications. Therefore, the utilization of a topical compounded medication can reduce the production of proinflammatory cytokines and affect opioid receptors, calcium channel blockers, sodium channel blockers, glutamate receptors and other receptor sites involved in the transmission or production of pain.
Many patients with diabetes are also taking medications for a variety of comorbid conditions. These patients may be less than ideal candidates for anti-inflammatories due to declining renal function, a history of gastrointestinal pathology or coexisting hypertension. Similarly, a variety of significant drug interactions may occur between antidepressants, anticonvulsants, opioid analgesics and the medications that the patient with diabetes is taking not only for the management of diabetes but for a variety of comorbidities. Other factors such as renal dysfunction may limit the dosage of antinociceptive medications. Utilization of the same medications topically in compounded form significantly reduces the risk of drug interactions in these patients. Compounding also increases the possibility of providing pain relief in these patients while reducing the risks of adverse sequelae.
Examples of pain inhibitory activity affected by the use of compounded medication include stimulation of opioid receptors and effects on adenosine, cannabinoid receptors, gamma-aminobutyric acid (GABA), morphinan and somatostatin among other pain conducting blockade activities.
Conversely, the blockade of agents that will produce pain, such as bradykinin, prostaglandins, histamine, serotonin, adenosine triphosphate (ATP) and others, can occur at the same time. Accordingly, the administration of topically applied antinociceptive therapy offers the opportunity to provide pain relief via multiple mechanisms of action.
As a result, the patient benefits from the administration of pain management at multiple receptor sites while reducing the incidence of potential adverse sequelae. The healthcare provider can prescribe a topical mixture of agents that either interdict the production of substances initiating pain or concurrently interfere with the transmission of pain.
Topically applied medications for the treatment of diabetic neuropathy may concurrently include various mixtures of ketamine, gabapentin (Neurontin, Pfizer), clonidine, lidocaine, imipramine, doxepin (Silenor, Pernix Therapeutics), nifedipine (Procardia, Pfizer), anti-inflammatory medication, calcium channel blockers, vasodilators, muscle relaxants and other agents as the clinician determines to be appropriate.
As the plasma concentration of topically applied medications for the treatment of diabetic neuropathy is 5 to 15 percent of the corresponding oral medications, the incidence of side effects is dramatically lower than systemic use of the same medications.14
What Advantages Do Compounded Medications Provide?
The use of compounded medications for the treatment of diabetic neuropathy allows for optimization of drug concentration at the origin site of pain while providing lower systemic levels and a reduced risk of side effects. Additionally, few drug interactions exist when one utilizes the medications topically. Furthermore, titration of the medication, which one would typically employ with oral medications, is not required.
The use of compounded medication for the treatment of diabetic neuropathy allows the practitioner to individualize each prescription. One may utilize vasodilators when indicated and combine them with calcium channel blockers, local anesthetics, anticonvulsants or whatever agents the treating healthcare provider determines to be necessary. Similarly, clinicians can make compounded medications in strengths not typically available by oral administration. The use of these medications in a compounded form is helpful for patients who cannot swallow pills. These medications are also particularly helpful for the treatment of patients who are drug resistant and do not wish to take additional oral medications.
The utilization of compounded medications for the treatment of symptomatic neuropathy is part of an overall program for the treatment of diabetic neuropathy. Included in this overall program is proper management of diabetes and the use of supplements such as Metanx, carnitine, alpha lipoic acid or other agents to reverse the underlying metabolic defect, and prevent or reverse nerve damage. Additionally, decompression surgery may be helpful for the treatment of diabetic neuropathy.15
The basic principles guiding the treatment of diabetic neuropathy are:
• optimal management of diabetes;
• optimal management of the comorbid conditions that exacerbate diabetic neuropathy;
• reversal of metabolic deficits within the nerve;
• pain relief with analgesics or adjunctive analgesics, and physical therapy modalities; and
• evaluation for superimposed entrapment neuropathy.
What You Should Know About Topical Agents And Compounding
To a large extent, the selection of specific agents utilized for the topical compounded management of painful diabetic neuropathy is hit or miss. Physician experience and patient response determines the selection.
Anti-inflammatories. A variety of topically applied anti-inflammatory agents, such as ibuprofen, flurbiprofen, ketoprofen or diclofenac (Voltaren, Endo Pharmaceuticals), are in use in daily practice for the management of musculoskeletal pain. These agents work by the inhibition of prostaglandins such as PGE-2, which lower the threshold for pain conduction and act synergistically with other agents that initiate pain, such as bradykinin, serotonin or 5-hydroxytryptamine. The oral administration of these agents in the patient with diabetes may be limited as they may exacerbate concurrent renal dysfunction or hypertension. Compounding for neuropathy management may include such agents as diclofenac and ibuprofen although clinicians may utilize other topical anti-inflammatories.
Local anesthetics. I have found local anesthetic agents such as lidocaine, tetracaine or bupivacaine particularly helpful in the management of pain diabetic neuropathy. In addition, these agents provide local vasodilation, which may be helpful for the management of reduced neural vascular flow or in the treatment of painful neuropathic ulceration or vasospastic contributions to neuropathy pain. Typically, one utilizes a prescription of 5 to 10% for these agents.
Calcium channel blockers. Calcium channel blockers such as topical nifedipine or verapamil are vasodilators, and may increase neural vascular perfusion, contributing to the resolution of any ischemic neuropathy component. Concentrations of 2 to 15% are typical.
Gabapentin. Topical gabapentin may contribute to neuropathic pain relief while avoiding potentially troublesome neuropsychiatric side effects. Gabapentin contributes to pain relief by blocking the transmission of pain by interdiction of glutamate at the NMDA receptor and diminution of the AMPA receptor active through reduction of sodium channel activity. One typically prescribes 6% to 10% topical gabapentin.
Tricyclic antidepressants. Tricyclic antidepressants such as amitriptyline and imipramine, or drugs with tricyclic antidepressant-like activity such as cyclobenzaprine are effective in the management of painful diabetic sensory neuropathy. As adjuvant analgesics, these agents derive their activity from the interdiction of norepinephrine and 5-hydroxytryptamine uptake, binding to opioid receptor sites, blocking NMDA receptor sites, blockage of AMPA-Na receptor sites, and other activity such as that which occurs at muscarinic receptors. The topical concentration of tricyclic antidepressants is usually between 5 and 10%.
Baclofen. Baclofen, a muscle relaxant, may provide pain relief with topical administration. Baclofen exerts its analgesic activity through agonist activity for GABA-b and modulating neurotransmitter release by mimicking GABA. When including baclofen as part of a compounded prescription for topical application, a 2% concentration is typically required.
Clonidine. Clonidine is an alpha-2 agonist that blocks norepinephrine release to prevent the activation of peripheral adrenergic receptors. Use a 0.2% concentration when combining clonidine with other topical agents.
Ketamine. Not infrequently, physicians employ 5% to 10% ketamine as a part of the topical compounded treatment of painful diabetic sensory neuropathy. Ketamine efficacy derives from its NMDA-Ca channel blocking activity and blocking of peripheral NMDA receptors, thus interdicting pain transmission.
When it comes to compounding formulations for painful diabetic neuropathy, typical prescriptions include ketamine, verapamil, gabapentin, clonidine, lidocaine, imipramine, carbamazepine, baclofen, bupivacaine and cyclobenzaprine.
In Conclusion
Topical compounded medications may contribute to the resolution or decreased frequency and intensity of painful diabetic sensory neuropathy. They are typically part of a more global clinical approach to the management of painful diabetic sensory neuropathy. Topical compounding offers the potential benefits of site-directed treatment with reduced potential for adverse sequelae.
Dr. Jacobs is a Fellow of the American College of Foot and Ankle Surgeons, and a member of the Academy of Physicians in Wound Healing. He is in private practice in St. Louis.
Dr. Jacobs writes a DPM Blog for Podiatry Today, which you can read at www.podiatrytoday.com/blog/290 .
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http://www.podiatrytoday.com/compounding-meds-diabetic-neuropathic-pain-can-they-have-impact
