title: Tachykinin NK1 receptor antagonist RP67580 attenuates progressive hypersensitivity of flexor reflex during experimental inflammation in rats.
abstract: We have now examined whether the tachykinin NK1 receptor is involved in mediating progressive hypersensitivity of spinal flexor motoneurons induced by repeated peripheral stimulation of inflamed tissue in decerebrate-spinal rats. The mechanical threshold of spinal flexor motoneurons was significantly decreased, and the touch- and pinch-evoked responses significantly increased, 48 h after intra-plantar injection of 100 microliters complete Freund's adjuvant. The threshold was further progressively decreased and the touch- and pinch-evoked responses increased over the 80 min testing period. Subcutaneous injection of the tachykinin NK1 receptor antagonist RP67580 (2-[1-imino-2-(2-methoxy phenyl) ethyl]-7,7 diphenyl-4 perhydroisoindolone-(3aR,7aR)) (20 min prior to the beginning of the test) at 1 mg and 10 mg/kg significantly attenuated the progressive decrease of mechanical withdrawal threshold, and the progressive increase of the touch- and pinch-evoked responses. The inactive enantiomer RP68651 (2-[1-imino-2-(2-methoxy phenyl) ethyl]-7,7 diphenyl-4 perhydroisoindolone-(3aS,7aS)) at 1 mg and 10 mg/kg had no significant effect. The present results indicate that substance P and its preferred tachykinin NK1 receptor are involved in mediating progressive hypersensitivity during inflammation.
authors.affiliation: Department of Anatomy and Developmental Biology, University College London, UK. q.ma@ucl.ac.uk
authors.forename: Q P
authors.initials: QP
authors.lastname: Ma
authors.forename: C J
authors.initials: CJ
authors.lastname: Woolf
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects* / Q000502:physiology
chemical_list: D000700:Analgesics; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one