Sex-related differences in acute and chronic pain: a bench to bedside perspective

Abstract

Chronic pain affects the daily lives of millions. It has been estimated that nearly one-quarter of the world’s population suffers from chronic pain, making it the most common human health problem. The most recent estimates of the prevalence of chronic pain in Canada indicate that approximately 29% of the population experiences chronic pain, with nearly 80% of these people reporting their pain as moderate to severe. Interestingly, there is increased pain sensitivity and a higher prevalence of chronic pain conditions in females than in males. To date, however, there has been little basic research examining these sex differences from a mechanistic standpoint, with researchers either doubting or simply ignoring the evidence. Nevertheless, numerous studies and a recent review of the literature provide convincing evidence that there are indeed sex differences relating to chronic and acute pain. Sex differences have been examined in many areas of biological research, particularly in the field of molecular neuroscience. Numerous studies have shown somatic and hormonal sex differences at a molecular level, and these molecular differences between sexes are often reflected by differences in the outcome and progression of disease. This can been seen in Alzheimer’s disease, depression, Huntington’s disease, and cerebral ischemia, as well as in models of cognitive ability. Despite the well-described sex differences in pain and in other disease models, basic pain research has been slow to adopt systematic study of these differences. Common barriers to the study of sex differences in the basic mechanisms of pain include doubt for the need to study sex differences (an impact by conflicting studies devaluing the importance of sex studies), possible complications from different hormonal influences on behaviour, and the complexity of trying to determine the interacting roles of sex, pain, and the secondary factors associated with pain (e.g., depression). Dr. Jeffery Mogil of McGill University addressed these concerns in a recent review of both clinical and basic studies examining sex differences. Dr. Mogil presents strong evidence that there is indeed a prevalence of bias in pain towards females. Although not all studies found a statistically significant difference between the sexes, when examining the overall trends present in the data, the results overwhelmingly indicate that females suffer more than men from chronic pain disorders (e.g., back pain, migraine, osteoarthritis, widespread pain, and musculoskeletal, oral, and neuropathic pain). Also, trends in basic pain sensitivity in healthy human subjects have shown that females experience increased sensitivity to electrical stimulation, ischemic pain, cold and heat pain, pressure pain, and muscle pain. These findings are in contrast with a review of 122 studies examining sex differences in laboratory pain sensitivity where the results showed no overall sex differences . Dr. Mogil points out, however, that, upon closer examination of the review, it can be argued that rather stringent inclusion criteria were used to indicate a K. A. Mifflin, BSc B. J. Kerr, PhD Centre for Neuroscience, University of Alberta, Edmonton, AB, Canada