A Closer Look At Pharmacologic Compounds For Painful Diabetic Peripheral Neuropathy

Andrew H. Rice, DPM, FACFAS, and Sarah Edgar, DPM

The treatment of diabetic neuropathic pain is complex and often unsatisfactory clinical results plague the patient with diabetes and the treating physician. Historically, physicians have used systemic pharmacologic treatments with mixed results and undesirable side effects. These have included antidepressants, anticonvulsants, N-methyl-D-aspartate (NMDA) receptor antagonists and opiate analgesics.1

   More recently, topical pharmacologic compounds have started to play a role in the treatment of patients with diabetic neuropathic pain. Topical treatments offer a new multimodal arm in addressing chronic pain states as the treatments have limited absorption and an excellent safety profile in comparison to the systemic treatment options.2 These options offer an advantage over many of the medications physicians have used historically and can also offer benefits as adjunctive treatments.

   A consensus report from the International Association for the Study of Pain in 2010 suggested that topical analgesics may be beneficial in a setting of “localized neuropathic pain.”3 These topical medications are also beginning to serve as a treatment option for difficult to manage pain in patients with osteoarthritis, postherpetic neuralgia and complex regional pain syndrome.

   When one applies the topical medications to the skin, they exert their analgesic action by increasing drug concentration locally at the application site with minimal systemic uptake and low serum concentration. Given the complexity of treating neuropathic pain, topical analgesic formulations that use multiple agents with varied mechanisms of action may increase the efficacy of pain treatment and improve the chances of successful therapy.2

A Closer Look At Topical Compounds

A variety of medications are in common use as topical pain treatments. These modalities include nonsteroidal anti-inflammatory drugs (NSAIDs), local anesthetics, capsaicin, tricyclic antidepressants, ketamine and gabapentin (Neurontin, Pfizer) with options for use alone or in combination. In one study, 5% topical lidocaine applied as a patch or in a medicated plaster formulation were as successful in treating diabetic neuropathy as oral pregabalin, showing a 65 to 66 percent favorable response rate.4

   Adverse effects of these medications are minimal and avoid many of the complications associated with systemic treatments. Adverse effects of the topical treatments can include local skin rashes, itchiness and irritations.

   Compounded creams and ointments of topical analgesics use mixtures of water, glycerin, propylene glycol, methylparaben and conventional emulsifiers as carriers of the active substance.4

   The formulation we use in our treatment population is delivered through a vehicle that is a proprietary mixture of base components called Lipoderm ActiveMax (Professional Compounding Centers of America). This theoretically delivers a greater local response to the tissues by the active compounds included within the QmedRx diabetic peripheral neuropathy pain pharmaceutical topical cream, and effectively allows the delivery of a number of compounds simultaneously through the human skin. With this system, dosing accuracy and uniformity occur through a specific QmedRx pump bottle.

Case Studies In Using Compounds For Neuropathy

We would like to present three brief case presentations using identical pain compounds from the QmedRx Pharmacy. Each individual used an equal volume of pain cream three to four times per day on the bilateral lower extremities. The cream consisted of lidocaine 2%, prilocaine 2%, topiramate 2.5% and meloxicam 0.09%.


There are podiatrists who now use low dose bupivacaine (local anesthetic) in the form of ankle blocks to treat somatic sensory peripheral neuropathy in the feet. It is administered twice weekly for 2 to 2,5 months. Excellent symptomatic treatment. Low dose bupivacaine acts as an analgesic by inhibiting over expressed over active sodium ion channels in axons of neuropathic somatic sensory peripheral nerves. It is these overactive overexpressed sodium ion channels that create sub-threshold oscillation membrane potentials that are the spontaneous aberrant electrical signals that are transmitted to the somatosensory cortex of the brain, which then manifest as the somatic sensory symptoms of burning, pins and needles, and tingling in the feet as well as numbness. Low dose bupivacaine ankle blocks are used in conjunction with EST (electrical signal treatment) and with TENS (transcutaneous electrical nerve stimulation) unit, generating excellent symptomatic relief from somatic sensory neuropathy.

Combination treatment (i.e. oral Lyrica + cutaneous Lidoderm Patches + low dose bupivacaine nerve blocks) is the best way to treat somatic sensory peripheral neuropathy in the feet. Such combination treatment is symptomatic treatment, not a cure, that the neuropathy patient needs for life as needed.

More placebo double blind studies (randomized control trials) are needed with these topical medications. The two RCTs published so far revealed that there is no medical evidence that these topical medications actually are medically necessary in treating neuropathy in the feet. There should be about 10 more published RCTs required to ascertain whether these topical medications are medically necessary or not. It is still premature to know for now with only two RCTs published.

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