Spinal A3 adenosine receptor activation acutely restores morphine antinociception in opioid tolerant male rats

Heather Leduc-Pessah, Cynthia Xu, Churmy Y. Fan, Rebecca Dalgarno, Yuta Kohro, Sydney Sparanese, Nikita N. Burke, Kenneth A. Jacobson, Christophe Altier, Daniela Salvemini, Tuan Trang

研究成果: ジャーナルへの寄稿学術誌査読

1 被引用数 (Scopus)

抄録

Opioids are potent analgesics, but their pain-relieving effects diminish with repeated use. The reduction in analgesic potency is a hallmark of opioid analgesic tolerance, which hampers opioid pain therapy. In the central nervous system, opioid analgesia is critically modulated by adenosine, a purine nucleoside implicated in the beneficial and detrimental actions of opioid medications. Here, we focus on the A3 adenosine receptor (A3AR) in opioid analgesic tolerance. Intrathecal administration of the A3AR agonist MRS5698 with daily systemic morphine in male rats attenuated the reduction in morphine antinociception over 7 days. In rats with established morphine tolerance, intrathecal MRS5698 partially restored the antinociceptive effects of morphine. However, when MRS5698 was discontinued, these animals displayed a reduced antinociceptive response to morphine. Our results suggest that MRS5698 acutely and transiently potentiates morphine antinociception in tolerant rats. By contrast, in morphine-naïve rats MRS5698 treatment did not impact thermal nociceptive threshold or affect antinociceptive response to a single injection of morphine. Furthermore, we found that morphine-induced adenosine release in cerebrospinal fluid was blunted in tolerant animals, but total spinal A3AR expression was not affected. Collectively, our findings indicate that spinal A3AR activation acutely potentiates morphine antinociception in the opioid tolerant state.

本文言語英語
ページ(範囲)251-264
ページ数14
ジャーナルJournal of Neuroscience Research
100
1
DOI
出版ステータス出版済み - 1月 2022
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 細胞および分子神経科学

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