A systematic literature review of 10 years of research on sex/gender and pain perception – Part 2: Do biopsychosocial factors alter pain sensitivity differently in women and men? Mélanie Racine a,b , Yannick Tousignant-Laflamme c , Lorie A. Kloda d , Dominique Dion e , Gilles Dupuis a,f , Manon Choinière b,g,⇑ a Department of Psychology, Université du Québec à Montréal, Montreal, Quebec, Canada b Centre de recherche, Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, Quebec, Canada c École de réadaptation, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada d Life Sciences Library, McGill University, Montreal, Quebec, Canada e Department of Family Medicine and Emergency, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada f Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada g Department of Anaesthesiology, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. article info Article history: Received 15 February 2011 Received in revised form 15 November 2011 Accepted 22 November 2011 Keywords: Sex Gender Pain sensitivity Biological factors Psychological factors Cognitive factors Social factors Past history Healthy subjects Experimental studies Systematic review abstract This systematic review summarizes the results of 10 years of laboratory research on pain and sex/gender. An electronic search strategy was designed by a medical librarian to access multiple databases. A total of 172 articles published between 1998 and 2008 were retrieved, analyzed, and synthesized. The second set of results presented in this review (129 articles) examined various biopsychosocial factors that may con- tribute to differences in pain sensitivity between healthy women and men. The results revealed that the involvement of hormonal and physiological factors is either inconsistent or absent. Some studies suggest that temporal summation, allodynia, and secondary hyperalgesia may be more pronounced in women than in men. The evidence to support less efficient endogenous pain inhibitory systems in women is mixed and does not necessarily apply to all pain modalities. With regard to psychological factors, depres- sion may not mediate sex differences in pain perception, while the role of anxiety is ambiguous. Cognitive and social factors appear to partly explain some sex-related differences. Finally, past individual history may be influential in female pain responses. However, these conclusions must be treated with much cir- cumspection for various methodological reasons. Furthermore, some factors/mechanisms remain under- studied in the field. There is also a need to assess and improve the ecological validity of findings from laboratory studies on healthy subjects, and perhaps a change of paradigm needs to be considered at this point in time to better understand the factors that influence the experience of women and men who suf- fer from acute or chronic pain. Ó 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. 1. Introduction Hundreds of laboratory studies on the role of sex in human pain perception have been published between 1998 and 2008, but it is difficult to draw a clear pattern of responses that distinguishes wo- men from men. As shown in our companion review published in this issue of Pain Ò [157], differences in pain sensitivity observed in healthy females (F) and males (M) are not always consistent across different experimental pain modalities or are absent. Clini- cally, however, it is well documented that women are more likely than men to report a variety of recurrent pains, in multiple body areas, which are often described as being more severe and frequent compared to men [17,60,132,194]. Therefore, numerous laboratory studies have been conducted to try to understand the mechanisms underlying these differences (see reviews by Fillingim [52], Fillin- gim et al. [60], Mogil [132], Myers et al. [134], Robinson et al. [164], Rollman et al. [168]). Until a few years ago, a large majority of studies used the terms ‘‘sex’’ and ‘‘gender’’ interchangeably. However, an important dis- tinction has been made between the 2 terms: ‘‘sex’’ refers to bio- logical differences between women and men according to their 0304-3959/$36.00 Ó 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.pain.2011.11.026 ⇑ Corresponding author at: Centre de recherche, Centre hospitalier de l’Université de Montréal (CRCHUM) À Hôtel-Dieu, Masson Pavilion, 3850 St. Urbain Street, Room 8-211, Montreal, QC, Canada H2W 1T7. Tel.: +1 514 890 8000x14082; fax: +1 514 412 7027. E-mail address: manon.choiniere@umontreal.ca (M. Choinière). PAIN Ò 153 (2012) 619–635 www.elsevier.com/locate/pain