Roles of endothelin ETA and ETB receptors in nociception and chemical, thermal and mechanical hyperalgesia induced by endothelin-1 in the rat hindpaw.
Evidence on the relative roles of endothelin ET(A) and ET(B) receptors in mediating the nociceptive and hyperalgesic actions of endothelin-1 is still fragmented and conflicting, due to variations between species and/or models. This study assesses the participation of ET(A) and ET(B) receptors on the nociceptive behavior and hyperalgesia to chemical (formalin), mechanical and thermal stimuli evoked by endothelin-1 injected into the rat hind-paw. Intraplantar (i.pl.) injection of endothelin-1 (1-30 pmol, 50 microl) induced dose-dependent nociceptive behaviors over the first hour. Endothelin-1 (3-30 pmol) also potentiated both phases of nociception induced by a subsequent ipsilateral i.pl. injection of formalin (0.5%, 50 microl). Endothelin-1, at 10 pmol, increased responses of the first phase (0-10 min) by 97% and of the second phase (15-60 min) by 120%, and similar degrees of potentiation were observed following 30 pmol of the peptide. Endothelin-1 (1-30 pmol) caused slowly developing long-lasting thermal and mechanical hyperalgesia with maximum effects at 10 and 30 pmol, respectively, reaching significance at 2-3h and remaining elevated for up to at least 8h after injection. Treatment with the selective ET(A) and ET(B) peptidic antagonists BQ-123 and BQ-788 (i.pl., both at 10 nmol, 3.5h after ET-1 injection) or with the non-peptidic antagonists atrasentan and A-192621 systemically (i.v., 10 and 20mg/kg, respectively) each caused significant reductions in endothelin-1-induced nociception, as well as chemical, thermal and mechanical hyperalgesia. Thus, the nociceptive and hyperalgesic effects induced by i.pl. endothelin-1 seem to be mediated by both ET(A) and ET(B) receptors.
Department of Pharmacology, Federal University of Santa Catarina, Center of Biological Sciences, SC, Brazil.
Emerson M
EM
Motta
Juliana G
JG
Chichorro
Pedro
P
D'Orléans-Juste
Giles A
GA
Rae
D000818:Animals; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D005557:Formaldehyde / Q000633:toxicity; D006614:Hindlimb; D006930:Hyperalgesia / Q000503:physiopathology*; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000502:physiology*; D044023:Receptor, Endothelin B / Q000502:physiology*
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D005557:Formaldehyde