Abstract
Morphine is generally used to treat chronic pain in clinic. But long-term use of morphine can inevitably induce analgesic tolerance and hyperalgesia. Caveolin-1 is reported to affect morphine-mediated signaling transduction. However, the action mechanism of morphine-induced analgesic tolerance is still unknown. In this study, morphine-induced analgesic tolerance model was established in Sprague–Dawley rats. The effects of Caveolin-1 blocking on neuroinflammation and ERK/c-JUN pathway were then explored. Morphine can remarkably elevate the expression level of Caveolin-1. Based on paw withdrawal latency behavior test, we found that Caveolin-1 blocking can effectively attenuate morphine-induced analgesic tolerance and neuroinflammation. Activation of ERK/c-JUN significantly reversed the above influences caused by Caveolin-1 blocking. Taken together, blocking of Caveolin-1 can attenuate morphine-induced inflammation and analgesic tolerance through inhibiting NLRP3 inflammasome and ERK/c-JUN pathway.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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LWL made main contributions that are as follows: Writing — original draft, funding acquisition, conceptualization, formal analysis, project administration; PJ WAS mainly responsible for the following work: Resources, writing — review and editing; Data curation, Investigation; LJQ was in charge of methodology, supervision, validation writing — review and editing; All authors read and approved the final manuscript.
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All animal experiments in this study were performed in strict accordance with the protocols stated in the Guide for the Care and Use of Laboratory Animals and were approved by the ethical committee of HuiZhou Municipal Central Hospital.
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Liu, W., Jiang, P. & Qiu, L. Blocking of Caveolin-1 Attenuates Morphine-Induced Inflammation, Hyperalgesia, and Analgesic Tolerance via Inhibiting NLRP3 Inflammasome and ERK/c-JUN Pathway. J Mol Neurosci 72, 1047–1057 (2022). https://doi.org/10.1007/s12031-022-01989-w
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DOI: https://doi.org/10.1007/s12031-022-01989-w