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Modulation of pain by [1DMe]NPYF, a stable analogue of neuropeptide FF, in neuropathic rats.

Abstract
The pain modulatory effects of (D-Tyr)L(Me-Phe)QPQRF-amide ([1DMe]NPYF), a stable analogue of neuropeptide FF were studied in rats with a chronic neuropathy induced by unilateral ligation of two spinal nerves. According to behavioral assessments, intrathecal (i.t.) administration of [1DMe]NPYF induced mechanical antiallodynic and thermal antinociceptive effects in a parallel and dose-dependent fashion, whereas following administration in the periaqueductal gray (PAG) it produced only mechanical antiallodynia. I.t. or PAG administration of FLFQPQRF, a non-amidated form of NPFF, or intraplantar injection of [1DMe]NPYF into the neuropathic paw had no effects. Electrophysiological results indicated that administration of [1DMe]NPYF suppressed responses of nociceptive spinal dorsal horn neurons in a submodality selective way and without an effect on their spontaneous activity; PAG administration predominantly suppressed brush-evoked responses and i.t. administration heat-evoked responses. The descending inhibitory effect by conditioning electrical stimulation of the PAG was enhanced by i.t. administration of [1DMe]NPYF. The reversibility of [1DMe]NPYF-induced effects by naloxone (1 mg/kg subcutaneously) depended on the submodality of test stimulation and the route of drug administration. The amplitude of the innocuous H-reflex was not changed by [1DMe]NPYF administered i.t. in control rats. The present results indicate that [1DMe]NPYF produces a selective attenuation of pain in neuropathic animals due to naloxone-sensitive or -insensitive central mechanisms depending on the submodality of pain and route of drug administration. The amide-group is essential for the [1DMe]NPYF-induced attenuation of pain.
AuthorsH Wei, P Panula, A Pertovaara
JournalBrain research (Brain Res) Vol. 900 Issue 2 Pg. 234-43 (May 11 2001) ISSN: 0006-8993 [Print] Netherlands
PMID11334803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Oligopeptides
  • tyrosyl-leucyl-N-methylphenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide
  • phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide
Topics
  • Animals
  • Behavior, Animal (drug effects)
  • Chronic Disease
  • Electric Stimulation
  • H-Reflex (drug effects, physiology)
  • Hot Temperature
  • Hyperalgesia (psychology)
  • Injections, Spinal
  • Nervous System Diseases (physiopathology, psychology)
  • Neurons (physiology)
  • Nociceptors (drug effects, physiology)
  • Oligopeptides (pharmacology)
  • Pain (physiopathology)
  • Periaqueductal Gray (physiopathology)
  • Rats
  • Reference Values
  • Spinal Cord (pathology, physiopathology)
  • Touch

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