Study: Pain's origins differ in males and females

March 5, 2018, University of Texas at Dallas
Research conducted by Dr. Ted Price BS’97 and colleagues in the Pain Neurobiology Research Group focused on a newly discovered pain mechanism related to D5 dopamine receptors. Credit: Ricardo Castrillón

New research from The University of Texas at Dallas supports the growing consensus that pain begins differently for men and women at the cellular level.

Dr. Ted Price BS'97, Dr. Salim Megat and their colleagues in the Pain Neurobiology Research Group recently found that a specific manipulation of receptors in the nervous system for the neurotransmitter dopamine impairs chronic in male mice, but has no effect on females.

Price, an associate professor of neuroscience in the School of Behavioral and Brain Sciences, said that the new findings add to the growing chorus of recent research indicating strong differences in pain's origins in males and females. The results were published in the Journal of Neuroscience.

"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."

Discovering Differences Once Overlooked

Price said that the discovery was set in motion by a dictate from the National Institutes of Health (NIH) four years ago. Previously, many preclinical experiments used only male animals due to their relative simplicity—lacking an estrus cycle for reproduction that modulates hormone levels. When the NIH indicated that it would require research to include both males and females, it cleared the way for these dimorphisms—differences between the sexes—to be discovered.

"We've been overlooking a key variable for a long time, and I'm as guilty as everyone else," Price said. "Professionally, we saw no reason to do it until 2014. But we're discovering that the NIH's decision was the right thing. Everyone I know doing these studies is finding new and interesting mechanisms that we've simply overlooked."

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."

Devising New Ways to Treat Pain

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."

Price admits that, in one respect, his own research findings frustrate him, due to which sex they favor.

"Discovering D5 receptors as a pain relief target upsets me in a way. Most are women, not men, so I would prefer to develop something that was certain to work in females," he said.

He's hoping that adding his research to the mounting evidence of sex dimorphism can help bring change in how pain alleviation is viewed—and eventual relief to sufferers regardless of their sex.

"The D5 mechanism discovery is not so important in and of itself," he said. "What's really important is that it's another very clear indication that there are extraordinarily strong mechanistic sex differences in how pain becomes chronic. When you take what everybody has done in the field, that theme is really something that we have to pay very close attention to, and I feel like it's going to lead to the breakthrough we all really want."

Explore further: Women's chronic pain is more complex, more severe

More information: Salim Megat et al. A Critical Role for Dopamine D5 Receptors in Pain Chronicity in Male Mice, The Journal of Neuroscience (2017). DOI: 10.1523/JNEUROSCI.2110-17.2017

Related Stories

Women's chronic pain is more complex, more severe

October 24, 2013
(Medical Xpress)—New research from the University of Adelaide has found that chronic pain in women is more complex and harder to treat than chronic pain in men.

Sex differences in brain activity alter pain therapies

March 2, 2017
A female brain's resident immune cells are more active in regions involved in pain processing relative to males, according to a recent study by Georgia State University researchers.

Poor sleep worsens link between PTSD, chronic pain in youth

February 4, 2018
(HealthDay)—Poor sleep worsens the association between posttraumatic stress disorder (PTSD) symptoms and chronic pain in youth, according to a study published in the January issue of the Journal of Pain.

Brain chemical may offer new clues in treating chronic pain

May 6, 2015
A chemical in the brain typically associated with cognition, movement and reward-motivation behavior—among others—may also play a role in promoting chronic pain, according to new research at The University of Texas at ...

Men and women could use different cells to process pain

June 30, 2015
We have known for some time that there are sex differences when it comes to experiencing pain, with women showing a higher sensitivity to painful events compared to men. While we don't really understand why this is, it seems ...

Neuroscientist finds potential new source for pain inhibition

April 4, 2016
A UT Dallas scientist has found a new neurological mechanism that appears to contribute to a reduction in pain.

Recommended for you

How do we lose memory? A STEP at a time, researchers say

March 23, 2018
In mice, rats, monkeys, and people, aging can take its toll on cognitive function. A new study by researchers at Yale and Université de Montréal reveal there is a common denominator to the decline in all of these species—an ...

Brain's tiniest blood vessels trigger spinal motor neurons to develop

March 23, 2018
A new study has revealed that the human brain's tiniest blood vessels can activate genes known to trigger spinal motor neurons, prompting the neurons to grow during early development. The findings could provide insights into ...

Being hungry shuts off perception of chronic pain

March 22, 2018
Pain can be valuable. Without it, we might let our hand linger on a hot stove, for example. But longer-lasting pain, such as the inflammatory pain that can arise after injury, can be debilitating and costly, preventing us ...

From signal propagation to consciousness: New findings point to a potential connection

March 22, 2018
Researchers at New York University have discovered a novel mechanism through which information can be effectively transmitted across many areas in the brain—a finding that offers a potentially new way of understanding how ...

Using simplicity for complexity—new research sheds light on the perception of motion

March 22, 2018
A team of biologists has deciphered how neurons used in the perception of motion form in the brain of a fly —a finding that illustrates how complex neuronal circuits are constructed from simple developmental rules.

Focus on early stage of illness may be key to treating ALS, study suggests

March 22, 2018
A new kind of genetically engineered mouse and an innovation in how to monitor those mice during research have shed new light on the early development of an inherited form of amyotrophic lateral sclerosis (ALS).


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.