Melatonin alleviates morphine analgesic tolerance in mice by decreasing NLRP3 inflammasome activation.

ABSTRACT: Morphine is frequently used for pain relief, but long-term morphine therapy in patients with chronic pain results in analgesic tolerance and hyperalgesia. There are no effective therapeutic treatments that limit these detrimental side effects. We found pretreatment with melatonin could decrease morphine-induced analgesic tolerance. There was a significant activation of the NLRP3 inflammasome in the prefrontal cortex and the peripheral blood of morphine-treated mice compared to control animals, which could be blocked by melatonin. The inflammasome activation induced by morphine was mediated by the microglia. SiRNA knockdown or pharmacological inhibition of the NLRP3 abolished the morphine-induced inflammasome activation. Co-administration of melatonin and low-dose morphine had better analge

SUBMITTER: Liu Q 

PROVIDER: S-EPMC7225735 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature