Inhibition by NK2 but not NK1 antagonists of carrageenan-induced preprodynorphin mRNA expression in rat dorsal horn lamina I neurons.
Previous evidence indicated that NK2 rather than NK1 receptors play a central role in mediating the electrophysiological responses of dorsal horn neurons to brief cutaneous stimuli such as noxious heat (but not noxious pinch) and moderately sustained stimuli such as mustard oil, topically applied over 10-20 min. The present experiments were designed to investigate, by in situ hybridisation histochemistry, a delayed genomic response in dorsal horn neurons (the expression of preprodynorphin mRNA induced by intraplantar carrageenan injection) and explore the role of NK1 and NK2 receptors in mediating this response. In anaesthetised rats with bilateral intraplantar injections of carrageenan, neurokinin receptor antagonists were administered unilaterally by prolonged ionophoresis into the superficial dorsal horn. The marked increase in preprodynorphin mRNA expression elicited by carrageenan was inhibited (both in terms of number of expressing cells and their level of expression) by NK2 but not NK1 antagonists.
Parker
R M
RM
Department of Preclinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Summerhall, UK.
Fleetwood-Walker
S M
SM
Rosie
R
R
Munro
F E
FE
Mitchell
R
R
D000818:Animals; D002351:Carrageenan / Q000494:pharmacology*; D004399:Dynorphins / Q000235:genetics*; D004594:Electrophysiology; D015870:Gene Expression; D017403:In Situ Hybridization; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D018041:Receptors, Neurokinin-2 / Q000502:physiology*; D012259:Ribonuclease, Pancreatic / Q000494:pharmacology; D013116:Spinal Cord / Q000378:metabolism*
D064729:Neurokinin-1 Receptor Antagonists; D010456:Peptides, Cyclic; D011498:Protein Precursors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C036448:pre-prodynorphin; C068459:L 659874; C076509:L 668169; D004399:Dynorphins; D002351:Carrageenan; D012259:Ribonuclease, Pancreatic