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 th e spinal cord but the roles of ET-A and ET-B receptors in the spinal c ord 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, Sara fotoxin S6c (an ET-B receptor-selective agonist) and 1H-indolyl)]propi onyl]amino-3-(2-pyridyl)propionic acid (FR139317, an ET-A receptor-sel ective antagonist) on the agitation behavior evoked by formaldehyde so lution injection and on the thermal nociceptive test. The s.c. injecti on of formaldehyde solution into the hind paw evoked a biphasic flinch ing (phase 1, 0-9 min; phase 2, 10-60 min) of the injected paw. For th e purpose of data analysis, phase 2 was further divided into two phase s (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-depende nt manner and this ET-1 effect was antagonized by FR139317. Intratheca l injection of either ET-3 or Sarafotoxin S6c enhanced the phase 2a fl inching behavior in a dose-dependent manner. Intrathecal injection of the highest doses of ET-1, ET-3 and Sarafotoxin S6c had no effect on t he thermal nociceptive test. These data indicate that ET-A and ET-B re ceptors have a powerful effect on spinal nociceptive processing evoked by formaldehyde solution injection but not that evoked by thermal sti mulation.