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Involvement of multiple μ-opioid receptor subtypes on the presynaptic or postsynaptic inhibition of spinal pain transmission
- Mizoguchi, Hirokazu, Takagi, Hirokazu, Watanabe, Chizuko, Yonezawa, Akihiko, Sato, Takumi, Sakurada, Tsukasa, Sakurada, Shinobu
- Peptides 2014 v.51 pp. 15-25
- analgesic effect, antagonists, capsaicin, mice, pain, substance P
- 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.