Potential Involvement of μ-Opioid Receptor Dysregulation on the Reduced Antinociception of Morphine in the Inflammatory Pain State in Mice

Journal of Pharmacological Sciences

Hirokazu Mizoguchi²  Shinobu Sakurada²  Tsukasa Sakurada¹  Yuta Aoki²  Kumiko Takeda²  Chizuko Watanabe² 

[1]First Department of Pharmacology, Daiichi College of Pharmaceutical Sciences, Japan

[2]Department of Physiology and Anatomy, Tohoku Pharmaceutical University, Japan

关键词: antinociception;    morphine;    inflammatory pain;    μ-opioid receptor;    protein kinase C;   

DOI  :  10.1254/jphs.13242FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(14)Cited-By(3)The antinociceptive effect of morphine in the inflammatory pain state was described in the von Frey filament test using the complete Freund’s adjuvant (CFA)-induced mouse inflammatory pain model. After an i.pl. injection of CFA, mechanical allodynia was observed in the ipsilateral paw. The antinociceptive effect of morphine injected s.c. and i.t. against mechanical allodynia was reduced bilaterally at 1 day and 4 days after the CFA pretreatment. The expression level of mRNA for μ-opioid receptors at 1 day after the CFA pretreatment was reduced bilaterally in the lumbar spinal cord and dorsal root ganglion (DRG). In contrast, the protein level of μ-opioid receptors at 1 day after CFA pretreatment was decreased in the ipsilateral side in the DRG but not the lumbar spinal cord. Single or repeated i.t. pretreatment with the protein kinase Cα (PKCα) inhibitor Ro-32-0432 completely restored the reduced morphine antinociception in the contralateral paw but only partially restored it in the ipsilateral paw in the inflammatory pain state. In conclusion, reduced morphine antinociception against mechanical allodynia in the inflammatory pain state is mainly mediated via a decrease in μ-opioid receptors in the ipsilateral side and via the desensitization of μ-opioid receptors in the contralateral side by PKCα-induced phosphorylation.

【 授权许可】

Unknown