title: Involvement of multiple µ-opioid receptor subtypes on the presynaptic or postsynaptic inhibition of spinal pain transmission.
abstract: The involvement of the μ-opioid receptor subtypes on the presynaptic or postsynaptic inhibition of spinal pain transmission was characterized in ddY mice using endomorphins. Intrathecal treatment with capsaicin, N-methyl-d-aspartate (NMDA) or substance P elicited characteristic nociceptive behaviors that consisted primarily of vigorous biting and/or licking with some scratching. Intrathecal co-administration of endogenous μ-opioid peptide endomorphin-1 or endomorphin-2 resulted in a potent antinociceptive effect against the nociceptive behaviors induced by capsaicin, NMDA or substance P, which was eliminated by i.t. co-administration of the μ-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP). The antinociceptive effect of endomorphin-1 was significantly suppressed by i.t.-co-administration of the μ2-opioid receptor antagonist Tyr-D-Pro-Trp-Phe-NH2 (D-Pro2-endomorphin-1) but not the μ1-opioid receptor antagonist Tyr-D-Pro-Phe-Phe-NH2 (D-Pro2-endomorphin-2) on capsaicin- or NMDA-elicited nociceptive behaviors. In contrast, the antinociceptive effect of endomorphin-2 was significantly suppressed by i.t.-co-administration of D-Pro2-endomorphin-2 but not D-Pro2-endomorphin-1 on capsaicin-, NMDA- or substance P-elicited nociceptive behaviors. Interestingly, regarding substance P-elicited nociceptive behaviors, the antinociceptive effect of endomorphin-1 was significantly suppressed by i.t.-co-administration of another μ2-opioid receptor antagonist, Tyr-D-Pro-Trp-Gly-NH2 (D-Pro2-Tyr-W-MIF-1), but not D-Pro2-endomorphin-1 or D-Pro2-endomorphin-2. The present results suggest that the multiple μ-opioid receptor subtypes are involved in the presynaptic or postsynaptic inhibition of spinal pain transmission.
authors: Hirokazu
authors: H
authors: Mizoguchi
authors: Hirokazu
authors: H
authors: Takagi
authors: Chizuko
authors: C
authors: Watanabe
authors: Akihiko
authors: A
authors: Yonezawa
authors: Takumi
authors: T
authors: Sato
authors: Tsukasa
authors: T
authors: Sakurada
authors: Shinobu
authors: S
authors: Sakurada
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D059225:Nociception / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology / Q000502:physiology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D009435:Synaptic Transmission
chemical_list: D000700:Analgesics; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013373:Substance P; C105294:endomorphin 2; D013004:Somatostatin; D016202:N-Methylaspartate; D002211:Capsaicin