Spinal serotonin receptors mediate descending facilitation of a nociceptive reflex from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat

Abstract

Electrical stimulation in the nucleus reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGCα) produces facilitation and/or inhibition of spinal nociceptive transmission in behavioral and electrophysiological studies. The present study examined spinal neurotransmitter receptors mediating descending facilitation from the NGC/NGCα. As previously demonstrated, electrical stimulation in the NGC/NGCα at low intensities(≊10 μA) produced facilitation and at greater intensitis (≊38 μA) inhibition of the tail-flick (TF) reflex. Intrathecal pretreatment with the non-selective serotonin (5-HT) receptor antagonist methysergide attenuated or completely abolished facilitation of th TF reflex produced by electrical stimulation in the NGC/NGCα; intrathecal pretreatment with atropine, phentolamine, naloxone or mecamylamine was without effect on stimulation-produced facilitation. Descending inhibition from the NGC/NGCα produced by electrical stimulation was attenuated or completely abolished by bilateral transection of the dorsolateral funiculi (DLF) of the cervical spinal cord. Descending facilitation produced by electrical stimulation, however, was unaffected or enhanced following DLF transections. Glutamate microinjections (1.7 nmol/0.17 μl) into the NGC/NGCα produced a rapid, repeatable and short-duration facilitation of the TF reflex in rats with bilateral DLF transections and such facilitation was attenuated by intrathecal pretreatment with methysergide, but not atropine, xylamidine (5-HT 2 selective receptor antagonist) or MDL-72222 (5-HT 3 selective receptor antagonist). These findings suggest that facilitation of the TF reflex from the activation of the cell bodies in the NGC/NGCα is mediated by a descending serotonergic pathway traveling in the ventrolateral funiculi and by spinal 5-HT 1 receptors.