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.

The purpose of this article is to review the sixteen published studies that examine associations between the perception of experimentally induced pain across menstrual cycle phases of healthy females. We also performed a meta-analysis to quantitatively analyze the data and attempt to draw conclusions. The results suggest that there are relatively consistent patterns in the sensitivity to painful stimulation. These patterns are similar across stimulus modality with the exception of electrical stimulation. The magnitude of the effect was approximately 0.40 across all stimulation. For pressure stimulation, cold pressor pain, thermal heat stimulation, and ischemic muscle pain, a clear pattern emerges with the follicular phase demonstrating higher thresholds than later phases. When the effect size was pooled across studies (excluding electrical) comparisons involving the follicular phase were small to moderate (periovulatory phase, d(thr) = 0.34; luteal phase, d(thr) = 0.37; premenstrual phase, d(thr) = 0.48). The pattern of effects was similar for tolerance measures. Electrical stimulation was different than the other stimulus modalities, showing the highest thresholds for the luteal phase. When the effect size was pooled across studies for electrical stimulation, effect sizes were small to moderate (menstrual (d(thr) = -0.37), follicular d(thr) = -0.30) periovulatory d(thr) = -0.61), and premenstrual d(thr) = 0.35) phases. This paper raises several important questions, which are yet to be answered. How much and in what way does this menstrual cycle effect bias studies of female subjects participating in clinical trials? Furthermore, how should studies of clinical pain samples control for menstrual related differences in pain ratings and do they exist in clinical pain syndromes? What this paper does suggest is that the menstrual cycle effect on human pain perception is too large to ignore.

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The primary purpose of this study was to investigate the influence of an individual's Gender Role Expectations of Pain (GREP) on experimental pain report. One hundred and forty-eight subjects (87 females and 61 males) subjects underwent thermal testing and were asked to report pain threshold, pain tolerance, VAS ratings of pain intensity and unpleasantness, and a computerized visual analogue scales (VAS) rating of pain intensity during the procedure. Subjects completed the GREP questionnaire to assess sex-related stereotypic attributions of pain sensitivity, pain endurance, and willingness to report pain. Consistent with previous research, significant sex differences emerged for measures of pain threshold, pain tolerance, and pain unpleasantness. After statistically controlling for age, GREP scores were significant predictors of threshold, tolerance, and pain unpleasantness, accounting for an additional 7, 11, and 21% of the variance, respectively. Sex remained a significant predictor of pain tolerance in hierarchical regression analyses after controlling for GREP scores. Results provide support for two competing but not mutually exclusive hypotheses related to the sex differences in experimental pain. Both psychosocial factors and first-order, biological sex differences remain as viable explanations for differences in experimental pain report between the sexes. It appears that GREP do play a part in determining an individual's pain report and may be contributing to the sex differences in the laboratory setting.

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