Aripiprazole: The antiallodynic and antihyperalgesic effects in chronic constriction injury-induced neuropathic pain and reserpine-induced fibromyalgia with possible mechanisms

Neuropathic pain, caused by peripheral or central nerve damage, and fibromyalgia, a chronic musculoskeletal disorder, require complex treatment approaches. This study evaluated the antiallodynic and antihyperalgesic effects of aripiprazole (1, 5, and 10 mg/kg, i. p.) in rats with chronic constriction injury-induced neuropathic pain and reserpine-induced fibromyalgia in female Sprague-Dawley rats, using electronic von Frey and Hargreaves tests. Dopaminergic, serotonergic, and opioidergic systems' roles were assessed through pre-treatment with sulpiride (50 mg/kg), WAY 100635 (1 mg/kg), and naloxone (1 mg/kg), respectively. The effect of aripiprazole was compared with 30 mg/kg pregabalin in the neuropathic pain model and 30 mg/kg duloxetine in the fibromyalgia model. Aripiprazole demonstrated significant antiallodynic and antihyperalgesic activity in both models. It did not change locomotor activity at a dose of 1 mg/kg but caused a decrease at a dose of 5 mg/kg. Dopamine D₂, serotonin 5-HT_1A, and opioidergic receptors contributed to aripiprazole's effects at varying levels. This study highlights the potential use of aripiprazole for managing neuropathic pain and fibromyalgia by targeting multiple receptor systems. The findings demonstrate the potential use of aripiprazole alone or as an adjuvant in the treatments of neuropathic pain and fibromyalgia.