The xanthine oxidase inhibitor allopurinol prevents thermal and mechanical hyperalgesia in a mouse model of peripheral mononeuropathy.

BACKGROUND

Allopurinol is a potent xanthine oxidase inhibitor commonly used to treat hyperuricemia and gout. Purines have been implicated in various mechanisms of pain modulation. This study investigated whether xanthine oxidase inhibition by allopurinol could enhance endogenous purinergic activity and produce antinociceptive effects in a neuropathic pain model in mice.

METHODS

Male mice received intraperitoneal injections of allopurinol (50–200 mg/kg) or vehicle (10% Tween 80) and were subjected to a partial sciatic nerve ligation (PSNL) model of neuropathic pain. Behavioral assessments evaluated thermal and mechanical hyperalgesia. The involvement of adenosine receptors was explored using specific antagonists. Locomotor activity was assessed to rule out motor impairment. Cerebrospinal fluid (CSF) samples were collected to quantify purine levels.

RESULTS

Allopurinol induced dose-dependent antinociceptive effects in the neuropathic pain model. The antinociceptive response was partially reversed by the A1 adenosine receptor antagonist DPCPX, but not by the A2A antagonist SCH58261. No significant motor deficits were observed at doses up to 200 mg/kg. Biochemical analysis revealed increased CSF concentrations of xanthine, inosine, and guanosine, and decreased uric acid levels following allopurinol administration.

CONCLUSIONS

Systemic administration of allopurinol produced antinociceptive effects in a neuropathic pain model, with significant reductions in mechanical allodynia and effects on thermal hyperalgesia mediated partly by A1 adenosine receptors, as evidenced by main treatment effects and specific time-point differences where interactions were significant. These effects were accompanied by altered CSF purine levels without motor impairment. The findings support further investigation of xanthine oxidase inhibitors, such as allopurinol, as potential therapeutic agents for chronic neuropathic pain.