Injury. 2025 Nov 26;57(2):112908. doi: 10.1016/j.injury.2025.112908. Online ahead of print.

INTRODUCTION: 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.

AIM: This study evaluates the effects of varenicline as an add-on therapy to meloxicam in a rat model of ANI.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

PubMed:41317660 | DOI:10.1016/j.injury.2025.112908