Biopsychosocial contributions to sex differences in pain.

Abstract

Women are at greater risk for pelvic and abdominal pain, compared with men, as discussed in the commentary by Curran. Indeed, women are at greater risk for most common forms of chronic pain, which has prompted abundant research to elucidate potential sex differences in pain processing. The optimal theoretical model for conceptualising sex differences in pain is the biopsychosocial model. This model posits that the experience of pain is sculpted by complex bidirectional interactions among biological, psychological and social factors, and sex differences in pain provide an excellent example of the biopsychosocial model in action. Specifically, biological processes, including sex hormones, endogenous opioid function, and genetic contributions influence pain in a sex-dependent manner (Fillingim et al. J Pain 2009;10:447–85). Also, recent studies suggest that sex differences in brain structure and function between females and males may contribute to differences in the experience of pain, including visceral pain (e.g. Hong et al. J Neurosci 2014;34:14252–9). In addition, psychological processes, including mood/affect and coping, as well as social influences such as gender stereotypes are also known to contribute to sex differences in pain. These three sets of factors interact to impact pain in ways that remain poorly understood. Thus, it is important to recognise that sex differences in pain are real and driven by a complex web of causation. Understanding the nature and mechanisms underlying sex differences in pain has important implications for pain prevention and treatment. An important yet often overlooked aspect of sex differences in pain is qualitative sex differences. That is, notwithstanding whether men and women have different amounts of pain, the mechanisms driving the pain can be fundamentally different between sexes. For example, a recent translational study demonstrated that vasopressin activates endogenous analgesic mechanisms, except when they have already been activated by stress, as in males with high functioning of the AVPR1A receptor (Mogil et al. Nat Neurosci 2011;14:1569–73). This genotype by sex by stress interaction is an example of a qualitative sex difference, as the vasopressin by stress interaction only emerged in males. These findings also typify the complexity of biopsychosocial influences on pain. Another important issue to consider regarding sex differences in pain relates to pain treatment. Curran notes the potential for bias in the provision of treatment, with women at greater risk for undertreatment of pain. Such findings do exist and providers do well to acknowledge their potential biases and misconceptions and mitigate their intrusion into clinical care. However, on balance the literature does not suggest widespread gender bias in pain treatment. Another treatment consideration is whether some therapies are more effective for women than for men (or vice versa). Opioids may be more effective for women than men, particularly in the acute pain setting (Niesters, Pain 2010;151:61–8), and sex differences in response to other kinds of treatment remain understudied. Nonetheless, it seems plausible that sex-specific treatments for certain types of pain could emerge in the future. For now, an understanding of the biopsychosocial underpinnings of sex differences in pain will allow providers to approach pain in women from a more informed perspective. I have no conflicts of interest related to this mini-commentary.