More active ‘brain immune cells’ in regions involved in pain processing might explain why women aren’t as responsive to painkillers as men, a new paper concludes.

Image credits Wolfgang Claussen

Microglia — the brain’s resident macrophage cells — are tasked with keeping our intelligence-wielding soft bits safe and sound. But they may also make painkillers less efficient in the female brain, a new study has found. The paper shows that when microglia were blocked, female response to opioid pain medication raised to the level of pain relief seen in males.

Statistically speaking, women have a higher incidence of chronic and inflammatory pain conditions such as osteoarthritis. And it doesn’t help that pain medication just seems to work to a less degree for them. Severe chronic pain requires powerful drugs, the most powerful in use being morphine — but it is often reported to be less effective in females, who require larger doses for the same effect.

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“Indeed, both clinical and preclinical studies report that females require almost twice as much morphine as males to produce comparable pain relief,” said Hillary Doyle, graduate student in the Murphy Laboratory in the Neuroscience Institute of Georgia State. “Our research team examined a potential explanation for this phenomenon, the sex differences in brain microglia.”

Microglia are the resident brain immune cells. They keep watch in the brain for signs of pathogens or infections to gobble up and keep neurons in pristine working condition. But in female brains, these cells seem to treat morphine molecules as pathogens — since they interfere with normal body function — causing the release of inflammatory chemicals such as cytokines.

Previous studies have linked them with differences in perceived pain levels between the male and female brain, but the full scope of their effect remains unknown. To test their interaction with morphine, the team gave male and female rats a drug that inhibits microglia activation then treated them with the painkiller. Inhibiting the microglia “potentiated morphine antinociception in females such that no sex differences in [resistance] were observed,” the team reports.

“The results of the study have important implications for the treatment of pain, and suggests that microglia may be an important drug target to improve opioid pain relief in women,” said Dr. Anne Murphy, co-author on the study and associate professor in the Neuroscience Institute at Georgia State.

The full paper “Sex Differences in Microglia Activity within the Periaqueductal Gray of the Rat: A Potential Mechanism Driving the Dimorphic Effects of Morphine” has been published in The Journal of Neuroscience.