Inhibitory actions of endothelin-1 on pain processing.
Endothelin-1 (ET-1) in the central nervous system has been suggested to produce suppressive effects on pain transmission. We investigated the manner by which ET-1 exerts this action. ET-1 administered intracerebroventricularly produced a dose-dependent antinociceptive effect in a thermal pain test that utilized a spinal reflex to determine nociceptive thresholds. This suggested that the antinociceptive effect of ET-1 involved a descending pain inhibitory system. The antinociceptive effect was blocked by an ETA receptor antagonist but not by an ETB receptor antagonist, indicating that the action was mediated through the ETA receptor. Antagonists of opioid receptors, serotonin receptors, alpha-2 adrenergic receptors, oxytocin receptors, and dopamine receptors did not block the antinociceptive effect of ET-1. Thus, major descending inhibitory systems were probably not involved. The antinociceptive effect was blocked by intracerebroventricular administration of an alpha-1 adrenergic receptor antagonist. This indicated that the antinociceptive effect involved the activation of a supraspinal noradrenergic pathway, which in turn may activate a still unknown descending pain inhibitory system.
Hasue
Fumio
F
Department of Autonomic Physiology, Chiba University Graduate School of Medicine, Chiba, Japan.
Kuwaki
Tomoyuki
T
Yamada
Hiroaki
H
Fukuda
Yasuichiro
Y
Shimoyama
Megumi
M
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000008:administration & dosage / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D009842:Oligopeptides / Q000008:administration & dosage; D010146:Pain / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010456:Peptides, Cyclic / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage; D011224:Prazosin / Q000008:administration & dosage; D011930:Reaction Time; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D015016:Yohimbine / Q000008:administration & dosage
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018712:Analgesics, Non-Narcotic; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D018340:Receptors, Adrenergic, alpha-1; D015016:Yohimbine; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D011224:Prazosin