Analysis of the role of endothelin-A and endothelin-B receptors on nociceptive information transmission in the spinal cord with FR139317, an endothelin-A receptor antagonist, and sarafotoxin S6c, an endothelin-B receptor agonist.
Endothelin (ET)-A and ET-B receptors have been reported to exist in the spinal cord but the roles of ET-A and ET-B receptors in the spinal cord are poorly understood. To gain a better understanding of the roles of ET-A and ET-B receptors in nociceptive information transmission in the spinal cord, this study evaluated the effects of ET-1, ET-3, Sarafotoxin S6c (an ET-B receptor-selective agonist) and (R)2-[(R)-2-[(S)-2-[[1- (hexahydro-1H-azepinyl)]carbonyl]amino-4-methyl-pentanoyl]amino-3- [3-(1-methyl-1H-indolyl)]propionyl]amino-3-(2-pyridyl)propionic acid (FR139317, an ET-A receptor-selective antagonist) on the agitation behavior evoked by formaldehyde solution injection and on the thermal nociceptive test. The s.c. injection of formaldehyde solution into the hind paw evoked a biphasic flinching (phase 1, 0-9 min; phase 2, 10-60 min) of the injected paw. For the purpose of data analysis, phase 2 was further divided into two phases (phase 2a, 10-34 min; phase 2b, 35-60 min). Intrathecal injection of ET-1 depressed the phase 1 and 2 flinching behavior in a dose-dependent manner and this ET-1 effect was antagonized by FR139317. Intrathecal injection of either ET-3 or Sarafotoxin S6c enhanced the phase 2a flinching behavior in a dose-dependent manner. Intrathecal injection of the highest doses of ET-1, ET-3 and Sarafotoxin S6c had no effect on the thermal nociceptive test. These data indicate that ET-A and ET-B receptors have a powerful effect on spinal nociceptive processing evoked by formaldehyde solution injection but not that evoked by thermal stimulation.
Department of Anesthesiology, School of Medicine, Chiba University, Japan.
T
T
Yamamoto
N
N
Shimoyama
H
H
Asano
T
T
Mizuguchi
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D005557:Formaldehyde / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000819:agonists / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology*; D014757:Viper Venoms / Q000494:pharmacology*
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D017466:Receptors, Endothelin; D016194:Receptors, N-Methyl-D-Aspartate; D014757:Viper Venoms; C057354:sarafotoxins s6; C079574:FR 139317; D005557:Formaldehyde; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester