This study aimed to evaluate the effects of the cyclooxygenase-2 (COX-2) inhibitors rofecoxib and meloxicam, the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine hydrochloride, and their combinations on neuropathic pain in Sprague-Dawley rats. Neuropathic pain was produced by chronic constriction injury (CCI) of the right sciatic nerve in Sprague-Dawley rats under ketamine anesthesia. The analgesic effects of the ED?? doses of aminoguanidine hydrochloride, rofecoxib, and meloxicam administered orally were assessed using standard behavioural tests. In addition, combinations of aminoguanidine hydrochloride with rofecoxib or meloxicam were evaluated for their effects on neuropathic pain. Mechanical, thermal, and cold sensitivity tests confirmed the development of neuropathic pain following CCI. When administered individually, aminoguanidine hydrochloride, rofecoxib, and meloxicam significantly increased paw-withdrawal thresholds to mechanical stimuli at 6 hours in the ipsilateral hind paw. Combined treatment with aminoguanidine hydrochloride (30 mg/kg) and either rofecoxib (1.31 mg/kg) or meloxicam (1.34 mg/kg) produced a greater increase in mechanical pain thresholds at 6 hours. The combinations were more effective than individual treatments in reducing mechanical hyperalgesia. Combining aminoguanidine hydrochloride with meloxicam or rofecoxib may represent a promising therapeutic strategy for managing neuropathic pain.

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