Looking for Effective Treatment Options for Painful Diabetic Peripheral Neuropathy

Severe neuropathic pain due to diabetic peripheral neuropathy is associated with negative health impact and increased healthcare utilization, underscoring the need for the development of safe and effective treatments.

In “The Efficacy of Pregabalin in Patients with Moderate and Severe Pain Due to Diabetic Peripheral Neuropathy,” Emir and Parsons evaluated the efficacy of pregabalin in patients with moderate versus severe neuropathic pain due to diabetic peripheral neuropathy (DPN). The authors looked at data from 11 placebo-controlled trials of pregabalin for the treatment of DPN involving more than 3,000 patients (placebo n=1,047; pregabalin n=2,028). Patients treated with pregabalin received 150 mg, 300 mg, or 600 mg/day. Patients’ pain was evaluated on an 11-point scale, with scores of between 4 and 7 classified as moderate pain, and scores between 7 and 10 classified as severe. Researchers compared “pregabalin-mediated changes in pain, pain-related sleep interference (PSRI), and patient global impression of change (PGIC)” to the placebo group, and also between the moderate and severe pain groups.

Patients of all pain levels treated with pregabalin experienced significant reductions in pain scores from baseline to endpoint compared to placebo, across all doses. Patients with moderate or severe pain treated with 300 mg and 600 mg/day experienced significantly improved pain scores at endpoint, compared to placebo. Patients with severe pain treated with pregabalin 300 mg or 600 mg/day experienced improvements of a greater magnitude compared to placebo than did patients with moderate pain treated with pregabalin 300 mg or 600mg/day.

Pregabalin also “improved PRSI and PGIC in the moderate and severe groups compared to placebo, with greatest improvement occurring in the severe group.”

The authors wrote that “pregabalin was effective in DPN patients with both moderate and severe levels of pain. Patients with severe pain exhibited greater improvements in pain, PRSI and PGIC than patients with moderate pain, suggesting that pain severity may, in part, predict therapeutic response to pregabalin.”

The authors of “A Pilot Trial of Peripheral Nerve Decompression for Painful Diabetic Neuropathy,” looked at a non-pharmacologic approach to treatment of painful DPN, evaluating “the clinical and electrophysiologic outcomes of patients undergoing peripheral nerve decompression for painful diabetic neuropathies.”

Levine and colleagues noted thatdespite extensive research there is no clear understanding of the pathophysiology of diabetic neuropathy.” Approaches that decompress nerves that are often entrapped in diabetes have shown some promise. However, “there is no consensus on how entrapped nerves can be identified as nerve conduction studies (NCS) often do not detect abnormalities or may be difficult to reliably obtain.” There have been only limited prospective studies evaluating changes in symptoms and electrophysiology for these procedures. Nonetheless, patients who have undergone these procedures have reported some improvements in their pain.

The current study involved 10 patients with painful diabetic neuropathy who underwent peripheral nerve decompression. Patients’ initial pain and severity of their neuropathy were evaluated using HR-QOL, PGI, NPS, and BPI questionnaires during screening. Patients also underwent neurological and physical exams, skin biopsies for epidermal nerve fiber density, and NCS prior to their surgeries.

Surgeons used the Medtronic Nerve Integrity Monitor 3.0 to assess patients’ peroneal and tibal nerves during surgery pre- and post-decompression. Postoperative NCS and neurological exams were administered to all patients, with repeat follow-up at weeks 4 and 12 and additional skin biopsies and NCS at week 24.

The authors reported that “there is a clear trend for improvement in NCS even at sites where no compression was demonstrated pre-operatively, suggesting compression may be present in some nerves that cannot be demonstrated by routine NCS.” They also reported improvements in distal toe strength in some patients with toe extensor weakness. They concluded that “peripheral nerve decompression for painful diabetic neuropathy may have validity in the treatment of symptoms of diabetic neuropathy,” and that these results indicate that a larger controlled multi-center study is needed.