Experiments in rats may have revealed why some painkilling drugs are less effective in women compared with men.
US researchers found brain differences affecting the potency of opioids such as morphine.
The Journal of Neuroscience study also found drug effectiveness varied during the rats' menstrual cycles.
Another expert said it showed the growing importance of tailoring pain relief to match the individual needs of the patient.
However, the study from Georgia State University claims to be the first to pinpoint the reason why.
It looked closely at a tiny area of the brain called the periaqueductal grey area (PAG), which is important in the way that pain signals are interpreted.
Many neurons in this region have, on their surface, "receptors" designed to receive and lock onto the molecules found in opioid drugs.
These "mu-opioid receptors", when locked onto an opioid drug, send a message telling the brain to stop responding to pain signals, reducing the sensation of pain.
The Georgia State team found that, in the rat brain, females had a lower level of mu-opioid receptors in this part of the brain, suggesting that the potential potency of morphine is much reduced.
Additional tests suggested that the response to morphine varied depending on which part of the menstrual cycle the female rat was in.
Professor Anne Murphy, who led the research, said: "It is increasingly clear that morphine is significantly less potent in women compared with men - until now, the mechanism driving the phenomenon was unknown.
"Additional research with the inclusion of female subjects needs to be devoted to determining a more potent treatment for persistent pain in women."
Professor Karen Berkley, from Florida State University, described the research as "important" and called for more attention to be paid to make sure that women received adequate pain relief.
"What this research is trying to do is understand the hormonal influences on pain in women.
"Clinicians are becoming far more aware of this issue, certainly more than they were five or six years ago."
Human trials, already under way, would need to be concluded to confirm the results of this study, she said.