Response properties of neurons in the rostroventromedial medulla of neuropathic rats: Attempted modulation of responses by [1DMe]NPYF, a neuropeptideFF analogue
A. Pertovaara et al., Response properties of neurons in the rostroventromedial medulla of neuropathic rats: Attempted modulation of responses by [1DMe]NPYF, a neuropeptideFF analogue, NEUROSCIENC, 105(2), 2001, pp. 457-468
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.