New research supports the growing notion that the origin of pain differs at the cellular level between men and women. The research comes out of the University of Texas at Dallas and was published in the Journal of Neuroscience.
The research team found that a specific manipulation of receptors in the nervous system for the neurotransmitter dopamine impairs chronic pain in male mice, but has no effect on females.
Dr. Ted Price, an associate professor of neuroscience in the School of Behavioral and Brain Sciences, said that the new findings add to the growing consensus of recent research indicating strong differences in pain’s origins in males and females.
“For the same magnitude of pain in a male and a female, the mechanisms that drive pain seem to be remarkably separate,” Price said. “We’ve made a cellular change that completely reverses the genesis of the chronic pain in only the male. What we’re learning is that different types of cells drive the development of pain.”
The experiment focused on a newly discovered pain mechanism related to D5 dopamine receptors — one of five identified classes of receptors for the neurotransmitter. Mice genetically engineered to lack these D5 receptors showed significantly reduced pain responses — but only the males.
“It’s extraordinarily specific for males,” Price said. “If we see the same results in human tissues, it will support the idea that you could make a D5 antagonist drug to treat pain in men.”
Price added that this new research philosophy explains some of the inability to reproduce results in prior, single-sex studies.
“Those running clinical trials for the last five years have been frustrated because the preclinical results don’t come through in the clinical studies,” Price said. “The cause of this problem, potentially, is that up until recently, many of the preclinical investigators were just using males. Then, in the clinical trials, human participants are primarily female, because more women suffer chronic pain than men.”
The accelerating movement of research demonstrating profound differences between males and females may soon yield a new model for pain relief medication, Price said.
“It leads me to believe that it’s fairly likely we’ll want to make male- and female-specific drugs for chronic pain,” Price said. “If not that, we may need to develop diagnostics to look at an individual’s cell types that are prolonging pain, so we can tailor the therapeutic based on the underlying mechanism. We just don’t do that right now.”