Daily intermittent fasting in mice enhances morphine-induced antinociception while mitigating reward, tolerance, and constipation
Univ Arizona, Coll Med, Dept PharmacolIssue Date
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LIPPINCOTT WILLIAMS & WILKINSCitation
Duron, David I.; Hanak, Filip; Streicher, John M. Daily intermittent fasting in mice enhances morphine-induced antinociception while mitigating reward, tolerance, and constipation, PAIN: October 2020 - Volume 161 - Issue 10 - p 2353-2363 doi: 10.1097/j.pain.0000000000001918Journal
Copyright © 2020 International Association for the Study of Pain.Collection Information
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The opioid epidemic has plagued the United States with high levels of abuse and poor quality of life for chronic pain patients requiring continuous use of opioids. New drug discovery efforts have been implemented to mitigate this epidemic; however, new medications are still limited by low efficacy and/or high side effect and abuse potential. Intermittent fasting (IF) has recently been shown to improve a variety of pathological states, including stroke and neuroinflammation. Numerous animal and human studies have shown the benefits of IF in these disease states, but not in pain and opioid treatment. We thus subjected male and female CD-1 mice to 18-hour fasting intervals followed by 6-hour feed periods with standard chow for 1 week. Mice that underwent this diet displayed an enhanced antinociceptive response to morphine both in efficacy and duration using thermal tail-flick and postoperative paw incision pain models. While showing enhanced antinociception, IF mice also demonstrated no morphine reward and reduced tolerance and constipation. Seeking a mechanism for these improvements, we found that the mu-opioid receptor showed enhanced efficacy and reduced tolerance in the spinal cord and periaqueductal gray, respectively, from IF mice using a(35)S-GTP gamma S coupling assay. These improvements in receptor function were not due to changes in mu-opioid receptor protein expression. These data suggest that a daily IF diet may improve the therapeutic index of acute and chronic opioid therapies for pain patients in the clinic, providing a novel tool to improve patient therapy and reduce potential abuse.Note
12 month embargo; published 01 October 2020ISSN
Final accepted manuscriptae974a485f413a2113503eed53cd6c53
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