Why We Still Need To Speak About Sex Differences and Sex Hormones in Pain

In the world of pain, we must always consider the presence of gender. In nociception, as well as in pain, women are different from men in many, if not all, aspects of the system. Nociception is the sum of several events that occur from the periphery to the CNS, and there is much evidence that female nociception differs from male nociception. Moreover, it has to be considered that pain results from a male or a female cortex. Genetic, anatomical, physiological, hormonal, psychological, and social factors have been considered to explain the differences present at both levels. Notwithstanding all the evidence, it is still difficult to observe the application of this knowledge to the treatment of pain. Drugs are still given per kilogram, and clinical studies, albeit including women, often mix data from both sexes. Moreover, reports on these studies often fail to mention the women's age and reproductive status, i.e., sex hormones. Hormone levels vary from hour to hour, from day to day, and, as repeatedly confirmed, are affected by several pain killers commonly used in pain therapy. All the data confirm the urgent need to include sex differences and sex hormones among the key factors that play an important role in pain and pain treatment.