Spinal A 3 adenosine receptor activation acutely restores morphine antinociception in opioid tolerant male rats
| العنوان: | Spinal A 3 adenosine receptor activation acutely restores morphine antinociception in opioid tolerant male rats |
|---|---|
| المؤلفون: | Nikita N. Burke, Tuan Trang, Cynthia Xu, Kenneth A. Jacobson, Yuta Kohro, Rebecca Dalgarno, Christophe Altier, Sydney Sparanese, Churmy Y. Fan, Heather Leduc-Pessah, Daniela Salvemini |
| المصدر: | Journal of Neuroscience Research. 100:251-264 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Agonist, business.industry, medicine.drug_class, Analgesic, Central nervous system, Pharmacology, Adenosine, 03 medical and health sciences, Cellular and Molecular Neuroscience, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Nociception, Opioid, Morphine, Medicine, business, Nucleoside, 030217 neurology & neurosurgery, medicine.drug |
| الوصف: | 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 (A3 AR) in opioid analgesic tolerance. Intrathecal administration of the A3 AR 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-naive 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 A3 AR expression was not affected. Collectively, our findings indicate that spinal A3 AR activation acutely potentiates morphine antinociception in the opioid tolerant state. |
| تدمد: | 1097-4547 0360-4012 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::0490fb0a710206db70e1ad5d553f295d https://doi.org/10.1002/jnr.24869 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........0490fb0a710206db70e1ad5d553f295d |
| قاعدة البيانات: | OpenAIRE |
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