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.

Prior studies suggest manual therapy (MT) as effective in the treatment of musculoskeletal pain; however, the mechanisms through which MT exerts its effects are not established. In this paper we present a comprehensive model to direct future studies in MT. This model provides visualization of potential individual mechanisms of MT that the current literature suggests as pertinent and provides a framework for the consideration of the potential interaction between these individual mechanisms. Specifically, this model suggests that a mechanical force from MT initiates a cascade of neurophysiological responses from the peripheral and central nervous system which are then responsible for the clinical outcomes. This model provides clear direction so that future studies may provide appropriate methodology to account for multiple potential pertinent mechanisms.

Hypertonic saline preceded by a bronchodilator is an inexpensive, safe, and effective additional therapy for patients with cystic fibrosis. (ClinicalTrials.gov number, NCT00271310.)

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.