Tachykinin NK1 receptor antagonist RP67580 attenuates progressive hypersensitivity of flexor reflex during experimental inflammation in rats.
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.
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Q P
QP
Department of Anatomy and Developmental Biology, University College London, UK. q.ma@ucl.ac.uk
Woolf
C J
CJ
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
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