期刊
PEPTIDES
卷 51, 期 -, 页码 15-25出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2013.10.012
关键词
Endomorphins; Antinociception; R-Opioid receptors; NMDA receptors; NK1 receptors; Nociceptive behaviors; Spinal cord
资金
- JSPS KAKENHI [22600009, 24590731]
- MEXT (Ministry of Education, Culture, Sports, Science and Technology)
- Grants-in-Aid for Scientific Research [25460725, 22600009, 23590718, 24590731] Funding Source: KAKEN
The involvement of the mu-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 mu-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 it. co-administration of the mu-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 mu(2)-opioid receptor antagonist Tyr-D-Pro-Trp-Phe-NH2 (D-Pro(2)-endomorphin-1) but not the mu(1)-opioid receptor antagonist Tyr-D-Pro-Phe-Phe-NH2 (D-Pro(2)-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-Pro(2)-endomorphin-2 but not D-Pro(2)-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 mu(2)-opioid receptor antagonist, Tyr-D-Pro-Trp-Gly-NH2 (D-Pro(2)-Tyr-W-MIF-1), but not D-Pro(2)-endomorphin-1 or D-Pro(2)-endomorphin-2. The present results suggest that the multiple ti-opioid receptor subtypes are involved in the presynaptic or postsynaptic inhibition of spinal pain transmission. (C) 2013 Elsevier Inc. All rights reserved.
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