Gender differences in pain modulation by diffuse noxious inhibitory controls: a systematic review

Over the last decade, extensive research has demonstrated sex differences in pain perception and modulation. Several factors have been proposed to account for the differences observed between men and women, including pain modulation through diffuse noxious inhibitory controls (DNIC). Studies investigating sex differences in DNIC have shown mixed results, with some reporting decreased DNIC effect in women compared with men, while others found no difference in DNIC between the sexes. Additional studies have investigated DNIC in both sexes without focusing on sex differences. This systematic review aimed to answer the following question: "In humans of reproductive age without chronic pain, are women more likely than men to have decreased Diffuse Noxious Inhibitory Controls?" Relevant studies were identified by computerized searches of Pubmed/Medline, Embase, Biosis, Web of Science, PsycInfo and Cochrane (from January 1980 through February 2009). The search was limited to human studies with no language restriction. The initial search identified 718 titles and abstracts. Seventeen studies were included in the final stage and data regarding age and gender of participants, methodology and outcome measurements were extracted and analyzed. The majority of studies using pain report as the outcome found significantly more efficient DNIC in males than females (mean female/male ratio=0.54). Studies evaluating pain thresholds and nociceptive flexion reflex indicated the opposite when simply averaged across studies; however, weighted analyses of threshold found more efficient DNIC in males. Gender differences in DNIC effect depend on both the experimental methodology and the modes of measurement of the effect.