The brains of men and women process pain differently, necessitating distinct pain treatments, concludes a new study by Atlanta’s Georgia State University (GSU).

In fact, preclinical and clinical studies have shown that females require two to three times more morphine than males to produce comparable levels of analgesia, the report says. Such differences may be mediated by a different “activation” state of the immune system, leading the female brain to be less sensitive to pain killers, such as morphine.

The study,“Sex Differences in Microglia Activity within The Periaqueductal Gray of the Rat: A Potential Mechanism Driving the Dimorphic Effects of Morphine,” appeared in the Journal of Neuroscience.

Its findings may lead to the development of better therapeutic strategies to deal with pain in women, who are more likely to suffer  chronic and inflammatory pain conditions, including fibromyalgia.

“Indeed, both clinical and preclinical studies report that females require almost twice as much morphine as males to produce comparable pain relief,” Hillary Doyle, the study’s first author and a graduate student at GSU’s Neuroscience Institute, said in a news release. “Our research team examined a potential explanation for this phenomenon, the sex differences in brain microglia.”

Morphine exerts its pain control action by binding to a group of opioid receptors. However, morphine also affects the microglia, a type of immune system cells that protect the brain against the invasion of pathogens. By binding to protein receptors at the surface of microglia, morphine is interpreted by these cells as a pathogen, triggering an inflammatory response against itself.

Using rats, researchers found that, although there were no gender differences in microglia levels, females had more of these “activated” microglia than males. This difference in the “activation” state of microglia explained why females needed more morphine to get the same analgesic effect than males. It may also explain why chronic pain diseases such as fibromyalgia occur more frequently among women.

Interestingly, when researchers gave rats a molecule that blocks the binding of morphine to microglia, both males and females got equal pain relief at the same morphine concentration.

“The results of the study have important implications for the treatment of pain, and suggest that microglia may be an important drug target to improve opioid pain relief in women,” said Anne Murphy, the study’s senior author.