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Background  In addition to its classical effects on opioid receptors, morphine can activate glia and stimulate the production of pro-inflammatory immune molecules which in turn counteract the analgesic properties of morphine. We hypothesized that decreased morphine analgesia in females may be the result of exaggerated microglial activation in brain regions critical for analgesia.    Methods  Male and female rats were treated with morphine and/or minocycline and morphine analgesia was examined using the hot plate. We also examined the expression of microglial and astrocyte markers in the pain pathway.    Results  Males treated with minocycline, a microglial inhibitor, exhibited a significant increase in acute morphine analgesia as previously shown; however, morphine analgesia was not affected by minocycline pretreatment in female rats. Minocycline decreased the expression of glial activation markers in the male spinal cord and periaqueductal gray as expected; however, these same molecules were upregulated in the female.    Conclusions  These data describe a significant difference between males and females in the behavioral effects following co-administration of morphine and minocycline.

biology of sex differences

Examination of sex and minocycline treatment on acute morphine-induced analgesia and inflammatory gene expression along the pain pathway in Sprague–Dawley rats