A review examines why women experience more severe pain than men

This article is an excellent review describing the main findings regarding some of the pathophysiological mechanisms involved in primary visceral chronic pain. It is based on the established evidence that this type of pain is much more common in women, and this study primarily analyses the role played by different hormones in this process.

Hormonal influence shows a close correlation with pain and its chronicity via mechanisms of central sensitisation. Oestrogen levels in women increase visceral sensitivity via specific receptors in the internal organs. They influence the gut microbiome by inducing the production of certain metabolic products by the microbiome itself, which are responsible for the development of hypersensitivity to pain. Oestrogens also influence pain processing in various structures of the nervous system and modulate the activation of neuroimmune circuits in response to painful stimuli through the activation of immune cells, which differ between the sexes.

In other primary chronic pain syndromes — such as fibromyalgia, headaches and chronic pain associated with osteoarthritis, which are also much more common in women — the scientific evidence regarding the pathophysiological mechanisms involved is more limited, but they are likely to be the same and also attributable to hormonal differences.
Research into primary chronic pain is currently a very active field. Chronic pain is a condition that affects more than 20 per cent of the general population, with a particularly high prevalence amongst women, amongst whom the existence of this condition and the serious impact it has on their quality of life are often overlooked.

Unfortunately, current treatments for chronic pain are unable to manage this condition satisfactorily; however, new findings regarding the pathophysiological mechanisms involved in this process open the door to promising new strategies for the treatment of primary chronic pain.

This article reinforces what is already known—not only through common wisdom but also through scientific evidence: there are significant differences in pain responses between men and women, involving both sensory and emotional aspects.

It is a high-quality article that not only describes the epidemiological situation but also analyzes differences at the cellular, molecular, and immunological levels.

The study reinforces findings dating back to the mid-20th century, when research began into pain response differences between males and females in animal experiments, as well as between men and women in clinical studies. These differences involve purely sensory aspects—such as pain response thresholds and pain tolerance, which are higher in men than in women—as well as emotional differences linked to gender, that is, the roles of men and women in society.

The implication is that we should not treat pain generically; instead, treatment should be tailored to the individual's sex (regarding pharmacological and physiotherapeutic approaches) and gender (regarding psychological approaches).

Although research is becoming increasingly specific, the consistent translation of these findings into therapeutic practice has not yet occurred.

The study's main limitations stem not from the article itself, but from the very concept of chronic pain. It is a condition with both sensory and emotional components. The emotional component varies greatly among patients, regardless of whether they are men or women. Indeed, we must recognize that every instance of pain is unique—an expression of a sensation filtered through emotion. Therefore, no two experiences of pain are truly identical. On the other hand, regarding the translation to the treatment of patients with pain, from a pharmacological perspective, clinical trials—while including both men and women—rarely analyze drug response separately by sex, and few studies employ experimental protocols stratified by sex.