Pain: male-female differences may have a neural basis

Some cellular mechanisms involved in pain are sex -specific

Contrary to popular belief, gender differences in pain perception are not subjective. A study published today in the journal Brain by researchers from Carleton University and Laval University provides tangible proof of this. The team's work reveals that the neural mechanisms that lead to chronic inflammatory pain are not the same in men and women.

We have known for a long time that the prevalence of chronic pain is higher in women," says Yves De Koninck, from the Faculty of Medicine and the CERVO research centre at Laval University. For example, women account for about 90% of fibromyalgia cases. They are also twice as likely to suffer from headaches and migraines. They are also known to be more sensitive to mechanical, thermal, electrical and chemical stimuli. Strangely, research seems to have long ignored these gender differences.

Indeed, the vast majority of studies that have explored the neuronal causes of pain have not paid particular attention to women," says Professor De Koninck. "In animals, the studies have mainly been carried out in males. As for human studies, they have too often mixed male and female subjects indiscriminately.

Professor De Koninck's team and Professor Michael Hildebrand's team at Carleton University set out to fill this gap by studying the neural mechanisms underlying chronic inflammatory pain. To do this, they used spinal cord tissue taken from 10 women and 12 men after their death, as well as male and female rats, which they put in the presence of BDNF, a protein that increases sensitivity to pain.

Results?  BDNF stimulated the mechanisms leading to hypersensitivity in human male tissues and in male rats, but not in human female tissues or in female rats. "We did the same experiments on female rats that no longer produced sex hormones following ovarian resection. In these females, BDNF then produced the same effects as in males," emphasises Yves De Koninck.

Another study published last week in the Journal of Neuroscience by Professor De Koninck's team and Theodore Price's team from the University of Texas revealed another sex difference related to pain in mice and rats. This time the researchers looked at a peptide, CGRP, which is involved in migraine.

"Our experiments have shown that this peptide exacerbates pain in females, but not in males. This could explain why the prevalence of headaches and migraines is higher in women," says Professor De Koninck.

In addition to their importance for understanding the fundamental phenomena leading to chronic pain, the results of these studies deliver two important messages, says the researcher.

"The first message is that when designing our experiments, we need to keep in mind that there may be differences between the sexes. This means, among other things, providing enough subjects of each sex to be able to detect these differences."

The second message is that the search for new pain treatments must target mechanisms that are common to both sexes. "If there are none, we need to find effective targets for each gender and develop appropriate treatments."

Read the original version of this text by Jean Hamann (in French) on the ULaval nouvelles website

Read the original research article here:

Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain. Annemarie Dedek, Jian Xu, Louis-Étienne Lorenzo, Antoine G Godin, Chaya M Kandegedara, Geneviève Glavina, Jeffrey A Landrigan, Paul J Lombroso, Yves De Koninck, Eve C Tsai, Michael E Hildebrand. Brain. Published: 23 March 2022

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