Neurokinin-1 receptor in peripheral nerve terminals mediates thermal hyperalgesia.
Neurokinin-1 receptor (NK-1) plays an important role in nociception. The present study was to explore whether activation of peripheral NK-1 receptor, especially expressed on primary sensory afferents, could induce hyperalgesia and sensitize C-type sensory afferents. (1) Intraplantar administration of NK-1 agonist [Sar9, Met(O2)11]SP (Sar-SP, 0.2, 1 nmol, 20 microl) produced significant thermal hyperalgesia and edema, which was blocked by co-injection of NK-1 antagonist WIN51,708 (10 nmol). But in the rats with compound 48/80 treatment for mast cell depletion, the Sar-SP-induced edema, but not hyperalgesia, was attenuated. (2) Close-arterial injection of Sar-SP (1 nmol, 0.1 ml) excited and sensitized sensory C afferents of the sural nerve to heat stimuli. The results suggest involvement of NK-1 receptors expressed on the peripheral afferent terminals in thermal hyperalgesia mediated by directly sensitizing C-type sensory afferents.
Chen
Wen-Ling
WL
Institute of Neurobiology, Fudan University, Shanghai 200433, China.
Zhang
Yu-Qiu
YQ
Zhao
Zhi-Qi
ZQ
D000731:Androstanes / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D001562:Benzimidazoles / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D004487:Edema / Q000378:metabolism / Q000503:physiopathology; D006930:Hyperalgesia / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D009411:Nerve Endings / Q000378:metabolism*; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D013497:Sural Nerve / Q000187:drug effects / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000731:Androstanes; D001562:Benzimidazoles; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; C086111:WIN 51708; C062618:substance P, Sar(9)-Met(O2)(11)-; D013373:Substance P; D003189:p-Methoxy-N-methylphenethylamine