Response properties of neurons in the rostroventromedial medulla of neuropathic rats: Attempted modulation of responses by [1DMe]NPYF, a neuropeptideFF analogue

We determined whether chronic neuropathy changes response properties of neu rons in the rostroventromedial medulla of rats, and whether (d-Tyr)L(Me-Phe )QPQRF-amide, a neuropeptide FF analogue, in the periaqueductal gray produc es changes in responses of rostroventromedial medullary neurons that might underlie its antiallodynic effect described earlier. Single unit recordings of medullary neurons were performed in lightly anesthetized neuropathic an d control animals. Spontaneous activity and the responses to noxious therma l and mechanical stimulation of the hind paw were determined with and witho ut administration of (d-Tyr)L(Me-Phe)QPQRF-amide. The neurons were classifi ed into three groups: ON-neurons increased, OFF-neurons decreased, and NEUT RAL-neurons did not change their discharge rate prior to a limb withdrawal induced by noxious stimulation of the skin. Spontaneous activity and heat-e voked responses of ON-neurons were not different between neuropathic and co ntrol animals, whereas their mechanically evoked responses were reduced in neuropathy. Response properties of OFF-neurons were not different between n europathic and control animals, Spontaneous activity of NEUTRAL-neurons was not different between neuropathic and control animals. (d-Tyr)L(Mc-Phe)QPQ RF-amide in the periaqueductal gray had no significant effect on evoked res ponses or spontaneous activity of ON- or OFF-neurons, independent of the ex perimental group. However, (d-Tyr)L(Me-Phe)QPQRF-amide produced a significa nt attenuation of spontaneous activity of NEUTRAL-neurons in neuropathic an imals. In a behavioral study performed in unanesthetized animals it was fou nd that intrathecal administration of methysergide, a serotonin antagonist, selectively attenuated neuropathic symptoms. Also, light pentobarbitone an esthesia markedly attenuated, but did not abolish, behaviorally determined neuropathic symptoms. From these results we suggest that NEUTRAL-neurons of the rostroventromedia l medulla may have a role in neuropathy and they may be involved in attenua tion of mechanical hypersensitivity by (d-Tyr)L(Me-Phe)QPQRF-amide in the p eriaqueductal gray. It is proposed that in neuropathy the synaptic effects of descending impulses from medullary NEUTRAL-neurons on their axonal targe ts in the spinal cord are changed so that this contributes to mechanical hy persensitivity, due to mechanisms that are at least partly serotoninergic. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.