Study first to pinpoint why analgesic drugs may be less potent in females than in males

Dec 23, 2008

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, Ph.D.

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."

Source: Georgia State University

Explore further: Startup commercializing innovation to reduce neurotoxin that damages nerve cells, triggers pain

add to favorites email to friend print save as pdf

Related Stories

Regulators reject call for nuke plant shutdown

11 minutes ago

The Nuclear Regulatory Commission on Wednesday rejected a senior federal expert's recommendation to shut down California's last operating nuclear power plant until the agency can determine whether its twin reactors can withstand ...

Few critics as Nevada mulls Tesla tax breaks

21 minutes ago

The Nevada Legislature has adjourned the first day of a special session considering an unprecedented package of up to $1.3 billion in incentives to bring Tesla Motors' $5 billion battery factory to the state.

Graphene paints a corrosion-free future

41 minutes ago

The surface of graphene, a one atom thick sheet of carbon, can be randomly decorated with oxygen to create graphene oxide; a form of graphene that could have a significant impact on the chemical, pharmaceutical ...

Mexican 'water monster' salamander battles extinction

1 hour ago

Dubbed the "water monster" by the Aztecs, the axolotl salamander is battling extinction in the remnants of Mexico City's ancient lake, alarming scientists hoping mankind learns from its ability to regenerate organs.

Recommended for you

Cellular protein may be key to longevity

Sep 15, 2014

Researchers have found that levels of a regulatory protein called ATF4, and the corresponding levels of the molecules whose expression it controls, are elevated in the livers of mice exposed to multiple interventions ...

Gut bacteria tire out T cells

Sep 15, 2014

Leaky intestines may cripple bacteria-fighting immune cells in patients with a rare hereditary disease, according to a study by researchers in Lausanne, Switzerland. The study, published in The Journal of Experimental Me ...

T-bet tackles hepatitis

Sep 15, 2014

A single protein may tip the balance between ridding the body of a dangerous virus and enduring life-long chronic infection, according to a report appearing in The Journal of Experimental Medicine.

User comments : 0