sensitivity depends on sex ⋅ Inserm, From science to health

The hypothesis of a difference between women and men in pain, as well as in the response to analgesic treatments, is the subject of lively discussions. Researchers are currently exploring the mechanisms potentially involved.

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In 2004, the Stopnet survey, conducted among 30,155 people representing the general population, estimated the prevalence the so-called chronic pain, that is, pain that has lasted more than three months: they would affect 30% of adults. ” He epidemiological studies show that with age, these chronic pains also affect more and more people, adds Gisèle Pickering *, a pharmacologist specializing in pain in Clermont-Ferrand. Another key point is that women are overrepresented among people who claim to suffer from chronic pain. »Is Pain Influenced by Sex?

The question has shaken scientists for decades. ” It is true that some pains are specific to women, such as premenstrual, those related to endometriosis or vulvodynia.. There are also pains common to both sexes, but for which there is a preponderance in women: this is the case, for example, of fibromyalgia, which affects 1.6% of the French population. “There are many hypotheses to explain these differences, but none alone is sufficient to explain the phenomenon. The work of Robert B. Filligim of the University of California outlines the most compelling topics. For example, the expression of pain is influenced by social factors: women consult more easily and respond more readily to surveys than men, and hormones are also involved. estrogen it would increase women’s sensitivity to pain – defined as the minimum intensity threshold for a stimulus perceived as painful – while testosterone, which is more present in men, would decrease this sensitivity. ” The reality is that we are still far from understanding the underlying mechanisms of this different gender sensitivity.sums up Gisèle Pickering. Although we know that women are more sensitive to pain than men, and this, whatever the cause, we have a problem: studies done so far on the subject present methodologies that are difficult to compare. »

Gender affects the response to treatment

In addition to the difficulty of assessing the overall scope of highly heterogeneous studies, another question encourages researchers: If pain sensitivity varies by sex, is the response to pain treatments also different? Morphine is the reference analgesic used to relieve severe pain in humans. But it causes more or less significant side effects, and in particular a certain tolerance, that is, a reduction in its analgesic effect when administered regularly. To counteract this habit, the doses are increased, which is accompanied by an increase in the risks of addiction and overdose. At the Institute for Cellular and Integrative Neurosciences in Strasbourg, Yannick Goumon ** and Florian Gabel ** are trying to update, in mice, the mechanisms that may explain the differences related to sex in sensitivity to anti-inflammatory treatments. aging, in order to adapt them as best as possible and use the appropriate doses of morphine.

Central concept of its research, nociception: corresponds to all the nervous processes that allow to detect, transmit and integrate an alarm message after a stimulation that presents a potential or real danger to the organism. Pain arises from the conscious interpretation of this nociception … To understand how to modulate it, the researchers measured the latency time for the appearance of an avoidance reflex in the face of a painful stimulus. First under normal conditions, then after taking painkillers, such as morphine, which inhibits nociception and prolongs the latency period. ” In our experiments, the analgesic effects of morphine are different depending on the sex of the mice: females need significantly more morphine than males to have the same analgesic effect. Yannick Goumon says. females, versus 9 days in males.

A story of degradation

How do you explain these differences? The pharmacokinetics of morphine, that is, its fate in the body from its entry to its elimination, would play an important role. Its degradation is ensured by enzymes located mainly in the liver and intestines, and to a lesser extent in the brain. In humans, the main products of this transformation are two metabolites, morphine-3-glucuronide or M3G and morphine-6-glucuronide or M6G … while only M3G is found in mice. The latter molecule, contrary to the desired effects of morphine, increases sensitivity to pain. ” Morphine appears to be transformed into M3G in a much larger way in female rodents than in males. Thus, the morphine / M3G ratio is clearly inclined in the direction of a decrease in the analgesic activity of morphine in women. “, analyzes the scientist, whose team has confirmed this trend both at the peripheral level, through blood tests, but also at the central level, through samples taken from key brain regions of the nociceptive system, such as gray matter, periaqueduct or amygdala.

Sex differences to consider?

Thanks to these results obtained in mice, the researchers clarify a sexual dimorphism3 in the metabolism of morphine. If this is shown to be transposable to humans, it is possible that the doses currently used in the treatment of pain, mainly by weight, but indiscriminately by sex, may not be adapted to the patient’s metabolism. ” Future large-scale clinical trials are now needed to better understand the value or not of a dosage adjustment for better pain management. Gisèle Pickering considers.

These studies have been conducted, but in too heterogeneous cohorts, for example with people of different ages or weights, to draw reliable conclusions. ” The fight against pain has become a major public health problem and the hospital landscape is now trying to rethink that care. Unfortunately, doctors do not have all the information to make these changes in a comprehensive way. “In addition to morphine, this research also raises questions about all drugs,” added Yannick Goumon. Is the way they are used appropriate for women? It will be necessary at one time or another to reflect systematically on the medical care of women compared to men concludes the researcher.

Ratings :
* CIC Inserm 1405 / Clermont Auvergne University; Unit 1107 Inserm / Clermont Auvergne University, NeuroDol