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Potential involvement of μ-opioid receptor dysregulation on the reduced antinociception of morphine in the inflammatory pain state in mice.
J Pharmacol Sci. 2014; 124(2):258-66.JP

Abstract

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.

Authors+Show Affiliations

Department of Physiology and Anatomy, Tohoku Pharmaceutical University, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24553404

Citation

Aoki, Yuta, et al. "Potential Involvement of Μ-opioid Receptor Dysregulation On the Reduced Antinociception of Morphine in the Inflammatory Pain State in Mice." Journal of Pharmacological Sciences, vol. 124, no. 2, 2014, pp. 258-66.
Aoki Y, Mizoguchi H, Watanabe C, et al. Potential involvement of μ-opioid receptor dysregulation on the reduced antinociception of morphine in the inflammatory pain state in mice. J Pharmacol Sci. 2014;124(2):258-66.
Aoki, Y., Mizoguchi, H., Watanabe, C., Takeda, K., Sakurada, T., & Sakurada, S. (2014). Potential involvement of μ-opioid receptor dysregulation on the reduced antinociception of morphine in the inflammatory pain state in mice. Journal of Pharmacological Sciences, 124(2), 258-66.
Aoki Y, et al. Potential Involvement of Μ-opioid Receptor Dysregulation On the Reduced Antinociception of Morphine in the Inflammatory Pain State in Mice. J Pharmacol Sci. 2014;124(2):258-66. PubMed PMID: 24553404.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potential involvement of μ-opioid receptor dysregulation on the reduced antinociception of morphine in the inflammatory pain state in mice. AU - Aoki,Yuta, AU - Mizoguchi,Hirokazu, AU - Watanabe,Chizuko, AU - Takeda,Kumiko, AU - Sakurada,Tsukasa, AU - Sakurada,Shinobu, PY - 2014/2/21/entrez PY - 2014/2/21/pubmed PY - 2014/10/14/medline SP - 258 EP - 66 JF - Journal of pharmacological sciences JO - J. Pharmacol. Sci. VL - 124 IS - 2 N2 - 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. SN - 1347-8648 UR - https://www.unboundmedicine.com/medline/citation/24553404/Potential_involvement_of_μ_opioid_receptor_dysregulation_on_the_reduced_antinociception_of_morphine_in_the_inflammatory_pain_state_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/DN/JST.JSTAGE/jphs/13242FP DB - PRIME DP - Unbound Medicine ER -