Roles of the rostroventromedial medulla and the spinal 5-HT1A receptor in descending antinociception induced by motor cortex stimulation in the neuropathic rat

Electric stimulation of the primary motor cortex (M1) has been effective in suppressing pain-related responses in neuropathic as well as healthy control animals. We studied whether the rostroventromedial medulla (RVM) or the spinal 5-HT1A receptor contributes to antinociception induced by stimulation of M1 in neuropathic animals. Assessments of the noxious heat-evoked limb withdrawal reflecting spinal nociception was performed in rats with spinal nerve ligation-induced peripheral neuropathy under light pentobarbital anesthesia. Spinal antinociception induced by electric stimulation of M1 was reduced following block of the RVM with intramedullary injection of muscimol, a GABAA receptor agonist, or following intrathecal administration of WAY-100635, a 5-HT1A receptor antagonist. The results indicate that the RVM and the descending serotonergic pathway acting on the spinal 5-HT1A receptor contribute to spinal antinociception induced by M1 stimulation in neuropathic animals.