A systematic literature review of 10 years of research on sex/gender and experimental pain perception – Part 1: Are there really differences between women and men?

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Abstract

The purpose of this systematic review was to summarize and critically appraise the results of 10 years of human laboratory research on pain and sex/gender. An electronic search strategy was designed by a medical librarian and conducted in multiple databases. A total of 172 articles published between 1998 and 2008 were retrieved, analyzed, and synthesized. The first set of results (122 articles), which is presented in this paper, examined sex difference in the perception of laboratory-induced thermal, pressure, ischemic, muscle, electrical, chemical, and visceral pain in healthy subjects. This review suggests that females (F) and males (M) have comparable thresholds for cold and ischemic pain, while pressure pain thresholds are lower in F than M. There is strong evidence that F tolerate less thermal (heat, cold) and pressure pain than M but it is not the case for tolerance to ischemic pain, which is comparable in both sexes. The majority of the studies that measured pain intensity and unpleasantness showed no sex difference in many pain modalities. In summary, 10 years of laboratory research have not been successful in producing a clear and consistent pattern of sex differences in human pain sensitivity, even with the use of deep, tonic, long-lasting stimuli, which are known to better mimic clinical pain. Whether laboratory studies in healthy subjects are the best paradigm to investigate sex differences in pain perception is open to question and should be discussed with a view to enhancing the clinical relevance of these experiments and developing new research avenues. Copyright Â© 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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Studying sex and gender differences in pain and analgesia: a consensus report.

Joel D Greenspan, Rebecca Craft, Linda LeResche … (2007)

In September 2006, members of the Sex, Gender and Pain Special Interest Group of the International Association for the Study of Pain met to discuss the following: (1) what is known about sex and gender differences in pain and analgesia; (2) what are the "best practice" guidelines for pain research with respect to sex and gender; and (3) what are the crucial questions to address in the near future? The resulting consensus presented herein includes input from basic science, clinical and psychosocial pain researchers, as well as from recognized experts in sexual differentiation and reproductive endocrinology. We intend this document to serve as a utilitarian and thought-provoking guide for future research on sex and gender differences in pain and analgesia, both for those currently working in this field as well as those still wondering, "Do I really need to study females?"

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Sex differences in the perception of noxious experimental stimuli: a meta-analysis.

Lawrence Myers, Kasandra J-L Riley, J. E. M. Robinson … (1998)

Fillingim and Maixner (Fillingim, R.B. and Maixner, W., Pain Forum, 4(4) (1995) 209-221) recently reviewed the body of literature examining possible sex differences in responses to experimentally induced noxious stimulation. Using a 'box score' methodology, they concluded the literature supports sex differences in response to noxious stimuli, with females displaying greater sensitivity. However, Berkley (Berkley, K.J., Pain Forum, 4(4) (1995) 225-227) suggested the failure of a number of studies to reach statistical significance suggests the effect may be small and of little practical significance. This study used meta-analytic methodology to provide quantitative evidence to address the question of the magnitude of these sex differences in response to experimentally induced pain. We found the effect size to range from large to moderate, depending on whether threshold or tolerance were measured and which method of stimulus administration was used. The values for pressure pain and electrical stimulation, for both threshold and tolerance measures, were the largest. For studies employing a threshold measure, the effect for thermal pain was smaller and more variable. The failures to reject the null hypothesis in a number of these studies appear to have been a function of lack of power from an insufficient number of subjects. Given the estimated effect size of 0.55 threshold or 0.57 for tolerance, 41 subjects per group are necessary to provide adequate power (0.70) to test for this difference. Of the 34 studies reviewed by Fillingim and Maixner, only seven were conducted with groups of this magnitude. The results of this study compels to caution authors to obtain adequate sample sizes and hope that this meta-analytic review can aid in the determination of sample size for future studies.

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Sex differences in pain.

Karen Berkley (1997)

Are there sex differences in pain? For experimentally delivered somatic stimuli, females have lower thresholds, greater ability to discriminate, higher pain ratings, and less tolerance of noxious stimuli than males. These differences, however, are small, exist only for certain forms of stimulation and are affected by many situational variables such as presence of disease, experimental setting, and even nutritive status. For endogenous pains, women report more multiple pains in more body regions than men. With no obvious underlying rationale, some painful diseases are more prevalent among females, others among males and, for many diseases, symptoms differ between females and males. Sex differences in attitudes exist that affect not only reporting, coping, and responses to treatment, but also measurement and treatment. So many variables are operative, however, that the most striking feature of sex differences in reported pain experience is the apparent overall lack of them. On the other hand, deduction from known biological sex differences suggests that these are powerful sex differences in the operation of pain mechanisms. First, the vaginal canal provides an additional route in women for internal trauma and invasion by pathological agents that puts them at greater risk for developing hyperalgesia in multiple body regions. Second, sex differences in temporal patterns are likely to give rise to sex differences in how pain is "learned" and stimuli are interpreted, a situation that could lead to a greater variability and wider range of pains without obvious peripheral pathology among females. Third, sex differences in the actions of sex hormones suggest pain-relevant differences in the operation of many neuroactive agents, opiate and nonopiate systems, nerve growth factor, and the sympathetic system. Thus, while inductive analysis of existing data demonstrate more similarities than differences in pain experience between females and males, deductive analysis suggests important operational sex differences in its production.