Lidocaine Patch for Diabetic Neuropathy

Abstract & Commentary

Synopsis: Evidence suggests that Erythropoietin acts by stimulating neuroprotective pathways, including the protein kinase B cascade and the transcription factor nuclear factor-kB pathway, to activate antiapoptotic and antioxidant factors.

Source: Barbano RL, et al. Effectiveness, Tolerability, and Impact on Quality of Life of the 5% Lidocaine Patch in Diabetic Neuropathy. Arch Neurol. 2004;61:914-918.

Fifty-six patients with painful diabetic neuropathy of at least 3 months duration, volunteered for this open-label, flexible-dosing, 3-week study evaluating the effectiveness and tolerability of the 5% lidocaine patch. All patients rated their average daily pain as at least 4 out of 10 on the Brief Pain Inventory (BPI), were on a stable analgesic regimen for at least 1 week prior to the baseline visit, and demonstrated hemoglobin A1C less than 13. Exclusionary criteria included any other concomitant more painful condition, open skin lesions interfering with placement of the lidocaine patch, prior treatment with, or allergy to, topical lidocaine, alcoholism, suicide attempts or intent, and treatment with class 1 anti-arrhythmic agents. Treatment allowed for up to 4 patches to be placed over the entire painful area, if possible, for 18 hours of the day, with 6 hours off, for a period of 3 weeks. Evaluations included daily patient Brief Pain Inventory (BPI) ratings, short-form McGill Pain Questionnaires (MPQ), sleep quality assessments, Beck Depression Inventory scores, and Profile of Mood States mood scores. Change in mean-daily-pain diary rating was the primary outcome measure, with secondary outcome measures including the BPI, MPQ, quality of life, and safety and tolerability. Statistical analysis used a 2-way, repeated-measures analysis of variance and the McNemarr test, with P < 0.05 considered significant.

Significant improvement was seen in both primary and secondary outcome measures. Thirty-seven patients (66%) achieved at least 30% pain reduction over 3 weeks, 23 (41%) appreciating greater than 50% pain reduction. Sleep quality, BPI rating, Beck Depression Inventory scores, and Profile of Mood-States mood scores also improved. Among 28 patients treated an additional 5 weeks, 3 were able to completely discontinue concomitant analgesic medication (gabapentin, amitriptyline) and 4 maintained reduced dosage. Pain or burning at the application site was the only adverse effect deemed related to the study drug, and no systemic adverse events were reported. Painful diabetic neuropathy responded to the 5% lidocaine patch in this flexible-dosing, open-label study. Controlled trials are warranted to confirm this result.

Commentary

Given the limited success of available treatments for painful diabetic neuropathy, newer agents are ever being sought. Erythropoietin, a renal cytokine crucial to erythropoiesis, is also produced in the nervous system, possibly functioning as a neuroprotective agent. In streptozocin-induced diabetic rats, intra-peritoneal administration of erythropoietin has recently been shown to protect from, and reverse, experimental diabetic neuropathy, improving nerve conduction velocity, motor evoked potentials, Na/K ATPase activity, and pain thresholds, while preventing cutaneous nerve fiber loss (Proc Natl Acad Sci USA. 2004;101;823-828). What can it do for man? Evidence suggests that it acts by stimulating neuroprotective pathways, including the protein kinase B cascade and the transcription factor nuclear factor-kB pathway, to activate antiapoptotic and antioxidant factors (N Engl J Med. 2004;350;2516-2517). Human clinical trials should begin forthwith. We impatiently await the results. — Michael Rubin

Dr.Rubin, Professor of Clinical Neurology, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.