Modulation of pain by [1DMe]NPYF, a stable analogue of neuropeptide FF, in neuropathic rats.
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.
Wei
H
H
Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
Panula
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P
Pertovaara
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D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002908:Chronic Disease; D004558:Electric Stimulation; D006181:H-Reflex / Q000187:drug effects / Q000502:physiology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000523:psychology; D007278:Injections, Spinal; D009422:Nervous System Diseases / Q000503:physiopathology* / Q000523:psychology; D009474:Neurons / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D010487:Periaqueductal Gray / Q000503:physiopathology; D051381:Rats; D012016:Reference Values; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D014110:Touch
D009842:Oligopeptides; C080757:tyrosyl-leucyl-N-methylphenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide