期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 100, 期 1, 页码 203-219出版社
WILEY
DOI: 10.1002/jnr.24626
关键词
conditional knockout; microglia; morphine; opioid receptor; opioid-induced hyperalgesia; tolerance; withdrawal
资金
- Universite de Strasbourg
- Frame program Investissements d'Avenir [ANR-10-IDEX-0002-02, ANR-10-LABX-0030-INRT]
- European Union Seventh Framework Programme FP7-Health-2013-Innovation [1602919]
One major challenge in medicine is to develop potent pain therapies without the adverse effects of opiates. This study investigated the role of microglial mu opioid receptor (MOR) in opiate analgesic tolerance, opioid-induced hyperalgesia (OIH), and physical dependence. The researchers found that deleting MOR in microglia delayed morphine analgesic tolerance and abolished OIH in mice. Their results suggest that blocking microglial MOR could be a therapeutic target for opiate analgesia without the opiate adverse effects.
A major challenge in medicine is developing potent pain therapies without the adverse effects of opiates. Neuroinflammation and in particular microglial activation have been shown to contribute to these effects. However, the implication of the microglial mu opioid receptor (MOR) is not known. We developed a novel conditional knockout (cKO) mouse line, wherein MOR is deleted in microglia. Morphine analgesic tolerance was delayed in both sexes in cKO mice in the hot plate assay. Opioid-induced hyperalgesia (OIH) as measured in the tail immersion assay was abolished in male cKO mice, and physical dependence to morphine as assessed by naloxone-induced withdrawal was attenuated in female cKO mice. Our results show a sex-dependent contribution of microglial MOR in morphine analgesic tolerance, OIH, and physical dependence. In conclusion, our data suggest that blockade of microglial MOR could represent a therapeutic target for opiate analgesia without the opiate adverse effects.
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