The effects of neurokinin receptor antagonists on mustard oil-evoked activation of rat dorsal horn neurons.
Previous evidence indicated that brief nociceptive responses of neurons in laminae IV/V of both rat and cat dorsal horn are more readily inhibited by antagonists at NK2 rather than at NK1 neurokinin receptors. Further support for a role of spinal NK2 receptors in nociception has been provided from experiments assessing modulation of the nociceptive flexor reflex by tachykinins and activation of dorsal horn neurons by brief application of capsaicin to afferents. The present experiments were designed to compare the contribution of NK1 and NK2 receptors in dorsal horn to the sustained neuronal activity induced by peripheral application of the chemical algogen mustard oil (reported to be a selective activator of C afferents). In nearly all of the multireceptive laminae IV/V neurons tested, a selective NK2 receptor antagonist L 659,874 inhibited previously established mustard oil-induced activity. In contrast, two selective NK1 receptor antagonists L 668,169 and GR 82334 were only rarely effective. These results further underline the apparent importance of NK2 receptors in spinal nociceptive processing. NK1 receptors do not appear to play a major role in the present experimental protocol, but they may of course do so under different circumstances.
Munro
F E
FE
Department of Preclinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies, Summerhall, Edinburgh, UK.
Fleetwood-Walker
S M
SM
Parker
R M
RM
Mitchell
R
R
D000818:Animals; D008297:Male; D009149:Mustard Plant; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology; D010936:Plant Extracts / Q000037:antagonists & inhibitors*; D010938:Plant Oils; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*
D064729:Neurokinin-1 Receptor Antagonists; D010936:Plant Extracts; D010938:Plant Oils; D018041:Receptors, Neurokinin-2; C027793:mustard oil