Effects of varenicline as an adjunct to analgesic and anti-inflammatory therapy in acute nerve injury.

Abstract

Acute nerve injury (ANI) leads to significant neuropathic pain and functional impairment. Current treatments, including nonsteroidal anti-inflammatory drugs (NSAIDs) like meloxicam, provide symptomatic relief but have limited neuroregenerative effects. Varenicline, a nicotinic acetylcholine receptor (nAChR) agonist, has demonstrated neuroprotective and anti-inflammatory properties. This study evaluates the effects of varenicline as an add-on therapy to meloxicam in a rat model of ANI. Eighteen female Wistar rats were randomized into four groups: Control (CONT), Sham (SHAM), Acute Nerve Injury + Meloxicam (ANI+Melox), and Acute Nerve Injury + Meloxicam + Varenicline (ANI+Melox+VAR). Varenicline (2.5 mg/kg, s.c.) was administered alongside meloxicam (2 mg/kg, s.c.). Functional recovery, histopathological changes, and biochemical markers, including prostaglandins (PGE₂, PGI₂), substance P, IL-6, levels, were assessed after 30 days. Varenicline and meloxicam co-treatment significantly reduced inflammatory and pain biomarkers including prostaglandins, interleukin-6 and substance P, compared to meloxicam alone. Histopathological evaluation revealed enhanced Schwann cell proliferation, reduced fibrosis, and increased Bands of Büngner formation, suggesting nerve regeneration. Varenicline, as an adjunct to meloxicam, enhances neuroprotection, reduces inflammation, and promotes histological and biochemical indicators of regeneration in rats with acute sciatic nerve injury. Future studies should explore its long-term effects and potential as a monotherapy for peripheral nerve injuries.