Sex-related differences in pain

Abstract

This article provides an overview of sex-related differences in musculoskeletal pain and the role sex hormones and response to analgesic drugs may play in these differences. Some common pain conditions that include temporomandibular disorders, rheumatoid arthritis, fibromyalgia syndrome and tension-type and migraine headaches, show fairly marked sex-related differences in their occurrence, however, with the exception of rheumatoid arthritis, these pain conditions are also characterized by a lack of understanding of their basic underlying pathophysiology. The association of pain symptoms of these musculoskeletal pain conditions with the reproductive cycle of women is strongly suggestive of a role of the estrogens and/or progesterones, the main female sex hormones, in sex-related differences in pain. Nevertheless, an alternative suggestion that testosterone, the major male sex hormone, protects men from these chronic musculoskeletal pain conditions, has also been made. Indeed, emerging evidence suggests that both male and female sex hormones may contribute to the marked sex-related differences in the occurrence of certain musculoskeletal pain conditions. Men and women also appear to differ in response to pain treatment with certain analgesic drugs. The mechanistic basis for these sex-related differences is not entirely understood but sex hormones are thought to be one of the influencing factors. An improved understanding of mechanisms which underlie sex-related differences in musculoskeletal pain and response to analgesic drugs should permit improved pain management strategies for male and female musculoskeletal pain patients in the clinical setting.

Introduction

Pain is the number one reason people seek medical treatment and, with an estimated annual cost of 1 trillion US dollars per year, it is the most costly health problem [1]. However, men and women are not equally represented as sufferers of a number of common, debilitating chronic pain conditions. For example, more women than men are thought to suffer from tension-type and migraine headache, temporomandibular disorders (TMD), irritable bowel syndrome, rheumatoid arthritis (RA) and fibromyalgia syndrome (FMS), whereas more men than women seek treatment for cluster headaches, ulcers, pancreatitis and trigeminal post-herpetic neuralgia [2]. When men and women suffer from the same pain condition, women often report more severe, frequent, anatomically diffuse and longer lasting pain than men. Chronic pain from the muscles and/or joints (musculoskeletal pain) is one of the most common reasons for seeking medical treatment and is one of the sources of pain where the greatest differences between women and men have been identified. The purpose of this article is to provide an overview of musculoskeletal pain conditions that exhibit pronounced sex-related differences in their prevalence and discuss biological mechanisms that may contribute to these differences. In the present article, we will refer to male–female differences as sex-related rather than gender-related, as the latter term is better applied to a person's self-representation as a male or female. The discussion of psychological and social factors, which are thought to play an equally significant role in differences in the prevalence of certain pain conditions in men and women, is beyond the scope of the current article.