A female brain's immune cells are more active in regions involved in pain processing compared to males, says a study that could potentially explain why pain relievers are often found to be less effective in women.

The study, published in the Journal of Neuroscience, found that when microglia, the brain's resident immune cells, were blocked, female response to opioid pain medication improved and matched the levels of pain relief normally seen in males. The finding that microglia are more active in brain regions involved in pain processing may contribute to why the incidence rates for various chronic pain syndromes are significantly higher in females than males. While morphine continues to be one of the primary drugs used for the treatment of severe or chronic pain, it is often less effective in females.

"Indeed, both clinical and pre-clinical studies report that females require almost twice as much morphine as males to produce comparable pain relief," said Hillary Doyle from Georgia State University in the US. "Our research team examined a potential explanation for this phenomenon, the sex differences in brain microglia," Doyle said.

In healthy individuals, microglia survey the brain, looking for signs of infection or pathogens. In the absence of pain, morphine interferes with normal body function and is viewed as a pathogen, activating the brain's innate immune cells and causing the release of inflammatory chemicals such as cytokines. To test how this sex difference affects morphine analgesia, Doyle gave male and female rats a drug that inhibits microglia activation. "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 co-author Anne Murphy, Associate Professor at Georgia State.