such as "Introduction", "Conclusion"..etc
Investigators at Georgia State University's Neuroscience Institute and
Center for Behavioral Neuroscience are the first to identify the most
likely reason analgesic drug treatment is usually less potent in
females than males. This discovery is a major step toward finding more
effective treatments for females suffering from persistent pain.
"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 and member of the Center for
Behavioral Neuroscience, who conducted the research with Dayna Loyd,
Murphy recently solved the mystery with findings printed in the
December issue of The Journal of Neuroscience that show 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).
Located in the midbrain area, the PAG plays a major role in the
modulation of pain by housing a large population of mu-opioid receptor
expressing neurons. Morphine and similar drugs bind to these mu-opioid
receptors analogous to a 'lock and key' and, ultimately, tell the brain
to stop responding to pain signals to the nerve cells resulting in the
reduced sensation of pain.
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. This 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. Interestingly, when they
used a plant-derived toxin to remove the mu-opioid receptor from the
PAG, morphine no longer worked, suggesting 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," Murphy said. "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."
Murphy's work was supported by grants from the National Institutes of Health.
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