Chronic pain is harder to treat in women, but a new target offers hope

Chronic pain affects millions of people worldwide, but studies show that women experience it more frequently than men.

While both sexes develop chronic pain, the biological processes behind it can be different.

New research sheds light on why this happens, highlighting a distinct immune response in women that may contribute to their increased sensitivity to pain.

Neuropathic pain across genders

Scientists at the University of Calgary conducted a study to explore how neuropathic pain – which is caused by nerve damage – manifests differently in men and women.

The research was focused on allodynia, a condition where non-painful stimuli, such as a light touch or temperature change, become painful. This condition can be extremely difficult to manage, making effective treatment options essential.

“Chronic pain disproportionately affects women, yet preclinical studies largely focus on males, neglecting the distinct medical needs of women,” wrote the researchers.

“This disparity is striking in neuropathic pain, where women are over-represented as patients and current treatments are inadequate in alleviating mechanical allodynia, a debilitating feature of neuropathic pain.”

The study, carried out on rats and mice, revealed a key difference in how pain signals are processed. Both male and female rodents use pannexin 1 (Panx1) channels to communicate pain signals. However, the type of immune cells involved varies by sex.

In female rodents, Panx1 activation triggers the release of leptin, a hormone linked to heightened pain sensitivity.

The role of leptin in chronic pain

Dr. Tuan Trang is a professor in the Faculty of Veterinary Medicine at the University of Calgary and the study’s lead researcher.

“Both males and females develop pain, but each sex develops it through different means,” explained Dr. Trang. “This study identifies a very unique type of biological process through a specific immune cell that is distinctive to each sex.”

The connection between leptin and pain is not new. Studies dating back to the 1980s have documented higher leptin levels in female patients with chronic pain. However, this research provides new insights into how leptin contributes to pain at the cellular level.

“Injury to a nerve can be debilitating,” said Dr. Trang. “We know that a lot of preclinical research has been on male subjects. Consequently, treatments were often developed from a male-based understanding and may not be very effective in females.”

Personalized treatment for chronic pain

Experts recognize the challenges in treating chronic pain, particularly in women.

Dr. Lori Montgomery is a pain clinician and clinical associate professor at the University of Calgary’s Cumming School of Medicine.

“In the clinic, we’ve known for many years that women are more likely than men to suffer from chronic pain, and it’s often hard to know why some people respond to treatment and others don’t,” said Dr. Montgomery.

This research suggests that recognizing biological differences in pain processing may help develop more effective, personalized treatments.

“Both sex and gender are important factors that need a lot more investigation, but this latest research might prove to be one of the ways that we can personalize treatment for patients so that it’s more likely to be effective.”

The future of pain research

The results from this study have the potential to change chronic pain treatment forever.

Knowing how the differences between leptin and immune cells affect pain could result in more specifically targeted treatments, ultimately enhancing the lives of millions who endure chronic pain disorders.

Future studies might explore the creation of pain relief medication that is specifically designed for women.

Since most current pain drugs have been primarily tested on men, it will be necessary to conduct clinical trials to control for these biological factors.

Scientists are now starting to investigate whether current drugs might be altered or repurposed to more effectively target mechanisms of pain in women.

In addition, personalized medicine could be a key element of chronic pain treatment. Progress in genetic screening and biomarkers may allow clinicians to determine which patients are likely to respond to particular treatments.

This would limit the trial-and-error process of pain treatment for more efficient and effective therapies.

With ongoing research, medical professionals can potentially provide improved treatment options for patients, taking into account biological sex differences in pain management strategies.

The full study was published in the journal Neuron.

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