For the first time, scientists have found why analgesic drug treatment is usually less potent in females than males.
"Opioid-based narcotics (such as morphine) are the most widely prescribed therapeutic agents for the alleviation of persistent pain; however, it is becoming increasingly clear that morphine is significantly less potent in women compared with men. Until now, the mechanism driving the phenomenon was unknown," said Anne Murphy, Ph.D., a Georgia State Professor of Neuroscience, who conducted the research with Dayna Loyd, Ph.D.
In a recent study Murphy found that previously reported differences in morphine's ability to block pain in male versus female rats are most likely due to sex differences in mu-opioid receptor expression in a region of the brain called the periaqueductal gray area (PAG).
PAG, which is located in the midbrain area, plays a major role in the modulation of pain by housing a large population of mu-opioid receptor expressing neurons.
By binding to these mu-opioid receptors like a 'lock and key', morphine and similar drugs, tell the brain to stop responding to pain signals to the nerve cells resulting in the reduced sensation of pain.
By using a series of anatomical and behavioral tests, Murphy and Loyd were able to determine that male rats have a significantly higher level of mu-opioid receptors in the PAG region of the brain compared with females.
The higher level of receptors is what makes morphine more potent in males because less drug is required to activate enough receptors to reduce the experience of pain.
To their interest, using a plant-derived toxin to remove the mu-opioid receptor from the PAG, morphine no longer worked, indicating that this brain region is required for opiate-mediated pain relief.
Additional tests also found females reacted differently to morphine depending on the stage of their estrous cycle. These findings indicate that steroid hormones may affect mu-opioid receptor levels in the region of the PAG that are essential for analgesia and also suggest that the actions of morphine are estrous stage-dependent.
"Interestingly, sex is not the only factor that has been shown to affect the potency of various pharmacological agents. Recent studies have reported an influence of age and ethnicity, and further argue for the inclusion of a wide range of study subjects in pain management research," said Murphy.
He added: "In addition, despite the rapidly mounting evidence regarding the limitations of opiates in treating persistent pain, opioid-based drugs remain the primary pharmacological tool for pain management. Clearly additional research with the inclusion of female subjects needs to be devoted to determining a more potent treatment for persistent pain in women."
The study was published in the December issue of The Journal of Neuroscience.