Treating Painful Neuropathy Associated with Diabetes

  In today’s healthcare scene there are many etiologies of neuropathy. None, however, is more prevalent than that which is related to diabetes, considering the growing global epidemic of the disease. Significant diabetic neuropathy typically occurs within 10 years of diagnosis and can increase throughout disease progression. “Painful” diabetic neuropathy is said to affect approximately 30% of all patients who experience diabetic neuropathy and significantly impact quality of life.¹ Elevated blood sugars and the malevolent chemical changes cause impaired nerve function and damage the circulation to impacted nerves. This results in the classic symptoms of anesthesia and paresthesia: numbness, burning, tingling, “pins and needles,” and cramping sensations that are common among those patients who report to the wound clinic. These symptoms usually are at their worst during the evening hours and are especially problematic as a scenario of the anesthetic diabetic foot and its associated ulceration, infection, and risk of amputation. Treatment options for painful diabetic neuropathy have improved as our understanding of the complex pathology improves; however, the goals of treatment remain the same. Symptomatic relief of pain is the most obvious goal with peripheral neuropathy. This includes both short- and long-term medications as well as treatment plans designed to help the patient feel more comfortable. Slowing the progression of the disease is also necessary to prevent continued increase in required medication. Restoring function to the affected area of the body, as well as the body as a whole, is crucial to overall success. This article will discuss suggested treatment measures clinicians should know and can use to help alleviate neuropathic pain and improve quality of life.

Improving Patient Habits

  Trying to change a patient’s daily habits is one of the most frustrating challenges associated with treating diabetes and its complications. Before effective pharmaceutical therapy can be obtained, the diabetes should be brought under the best control possible. This consists of helping the patient establish sound glycemic control without variations, such as fluctuation of blood sugars, and reinforcing the importance of this standard through education. Consistently elevated glucose levels will only limit the results of treatment. Positive control measured with hemoglobin A1c and daily blood sugar reduces the overall risk of neuropathy. Exercise and weight loss further contribute to decreasing neuropathic pain, as does smoking cessation and limiting alcohol consumption. Patient education in these factors is also considered a must.

Topical & Oral Medications

  There are numerous benefits to beginning topical therapy when used in combination with compliant blood glucose levels. Unfortunately, most oral medications have associated drug interactions and side effects when administered. Topical preparations limit systemic absorption and can still deliver effective pain control.   Capsaicin, a product derived from hot chili peppers, is available as several over-the-counter strengths and brands and helps to reduce pain sensations by depleting substance P in the nerves.   Lidocaine patches are another way clinicians can locally treat isolated symptomatic areas, and the side effects are minimal.   Biofreeze, a menthol product, is available in gel, liquid, and spray form, and can be applied to areas of continued pain. Commonly dispensed by physicians, chiropractors, and physical therapists for an assortment of symptoms, Biofreeze seems to work well for neuropathy.   L-arginine, an amino acid that has been the subject of recent study, is available orally and topically in a variety of commercial preparations. It is thought to stimulate vasodilation, increasing oxygen content in cells and improving overall circulation.²   A compounding pharmacy can also produce variations of products containing muscle relaxants, NSAIDS, anesthetics, and even pain medication into a dose that is applied topically. Many of these components were formally only available in oral form, but we’ve now learned the side effects and drug interactions can be limited.   A variety of oral medications are currently available to help provide neuropathic pain relief when glycemic control and topical medications are not enough. Many of the traditional medications used off-label have provided the best results for years. Anti-seizure medications, such as gabapentin, carbamazepine, and, most recently, pregabalin are used to treat disorders involving seizures (such as epilepsy). In addition, these medications have long been used for treating peripheral neuropathy with great success and can be titrated to the appropriate dose. Another class of medications that has shown benefits in the treatment of neuropathy is antidepressants.   Amiltriptyline, imipramine, and nortriptyline work by interfering with the brain’s ability to interpret pain sensation. Initially, they are usually taken before bed and work well against overnight pain. Other antidepressants that inhibit reuptake of serotonin and norepinephrine, such as duloxetine, can also improve pain levels with fewer side effects. When necessary, opioid analgesics can be used for recalcitrant neuropathic pain. However, multiple side effects such as addiction, constipation, and sedation, as well as the need to increase the dose due to upregulation, make this class of medications less desirable.

Other Treatment Modalities

  Methylcobalamin provides the active forms of folic acid and vitamins B6 and B12 directly to the body for functions such as DNA production, cell reproduction, and homocysteine metabolism to support peripheral nerve and blood vessel health. It can be taken twice daily and has no reported side effects, and is effective in treating symptomatic neuropathy.   Methylcobalamin can also be used in combination with other pain medications with no significant interactions. Alpha-lipoic acid is a fatty acid and antioxidant that has also received attention lately. Studies are now underway in the area of its use for peripheral neuropathy. It can function in both water and fatty tissue, and therefore enter all parts of the nerve cell and protect it from damage while improving pain symptoms. Physical therapy modalities have also been shown to improve symptoms.   Treatments such as transcutaneous electrical nerve stimulation units and massage, as well as continued range-of-motion exercises, are important to maintain circulation. Anodyne Infrared Therapy Systems,® medical devices that are indicated to increase circulation and reduce pain, stiffness, and muscle spasm, emit infrared light from super-luminous light-emitting diodes across the therapy pads and are indicated for acute pain and poor circulation associated with both diabetes and vascular diseases. Studies indicate significant reduction in overall pain as well as being able to eliminate a patient’s dependence on pain medications.³4 takes multiple procedures, and results can vary per patient. Biofeedback is another alternative therapy in which patients are taught how to control certain body responses that reduce pain. These special machines are typically limited to larger hospitals and medical centers, and data has been found to be inconsistent. Spinal cord stimulators may offer assistance in the future for severe cases. Lastly, a nerve decompression technique pioneered by A. Lee Dellon, MD, PhD, has also been shown to improve peripheral neuropathy symptoms in patients when their neuropathy is due to a nerve entrapment, as is seen in diabetic neuropathy with associated nerve swelling. The procedure has been performed within institutions around the world with success.⁵

References

1. Abbott CA, et al. Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K. Diabetes Care. 2011;34(10):2220-2224. 2. Fossel, E. Improvement of temperature and flow in feet of subjects with diabetes with use of a transdermal preparation of l-arginine: a pilot study. Diabetes Care. 2004;27(1):284-285. 3. Nawfar SA, Yacob NB. Effects of monochromatic infrared energy therapy on diabetic feet with peripheral sensory neuropathy: a randomised controlled trial. Singapore Med J. 2011;52(9):669-72. 4. Boulton AJM, Malik RA, Arezzo JC, Sosenko JM. Diabetic somatic neuropathies. Diabetes Care. 2004;27(6):1458-1486. 5. Cornblath DR. Surgical decompression for diabetic sensorimotor polyneuropathy. Diabetes Care. 2007;30(2):421-422.

Additional Resources

Jacobs AM. Orally administered l-methylfolate, methylcobalamin, and pyridoxal 5’-phosphate reduces diabetic peripheral neuropathic pain. Abstracts of New Cardiovascular Horizons Meeting. Oral Presentation, 2008. Bowker JH, Pfeifer MA. Levin and O’Neal’s The Diabetic Foot, 6th Ed. 2001:33-64. Yao P, et al. Sustained-release oxycodone tablets for moderate to severe painful diabetic peripheral neuropathy: a multicenter, open-labeled, postmarketing clinical observation. Pain Med. 2012;13(1):107-114. Ormseth MJ, Scholz BA, Boomershine CS. Duloxetine in the management of diabetic peripheral neuropathic pain. Patient Prefer Adherence. 2011;5:343-356. Hartemann A, et al. Painful diabetic neuropathy: diagnosis and management. Diabetes Metab. 2011;37(5):377-388. Chen W, Zhang Y, Liu JP. Chinese herbal medicine for diabetic peripheral neuropathy. Cochrane Database Syst Rev. 2011;15(6):CD007796. Mittal M, et al. Retrospective chart review of duloxetine and pregabalin in the treatment of painful neuropathy. Int J Neurosci. 2011;121(9):521-7. Chen S, et al. Factors associated with pain medication selection among patients diagnosed with diabetic peripheral neuropathic pain: a retrospective study. J Med Econ. 2011;14(4):411-420. Webster LR, et al. Efficacy, safety, and tolerability of NGX-4010, capsaicin 8% patch, in an open-label study of patients with peripheral neuropathic pain. Diabetes Res Clin Pract. 2011;93(2):187-197. Pinzur MS. Diabetic peripheral neuropathy. Foot Ankle Clin. 2011;16(2):345-349. Richard Kobylar is a podiatrist who practices in Baytown, TX. He may be reached at houstonfootdoctor@yahoo.com.