Pain
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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. ⋯ 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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A computer and a hand search of the literature recovered 33 papers from which 25 trials suitable for meta-analysis were identified. We compared the effectiveness of cognitive-behavioural treatments with the waiting list control and alternative treatment control conditions. There was a great diversity of measurements which we grouped into domains representing major facets of pain. ⋯ Differences on the following domains were not significant; mood/affect (depression and other, non-depression, measures), cognitive coping and appraisal (negative, e.g. catastrophization), and social role functioning. We conclude that active psychological treatments based on the principle of cognitive behavioural therapy are effective. We discuss the results with reference to the complexity and quality of the trials.
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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. ⋯ 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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Meta Analysis
Systematic review of factors affecting the ratios of morphine and its major metabolites.
In a systematic review of 57 studies with information on 1232 patients we examined the effect of age, renal impairment, route of administration, and method of analysis on the ratios of morphine-3-glucuronide:morphine (M3G:M) and morphine-6-glucuronide:morphine (M6G:M) and the relative concentrations of M3G and M6G. Across all studies the range of the ratios of metabolites to morphine was wide (0.001-504 for M3G:M, and 0-97 for M6G:M). Neonates produced morphine glucuronides at a lower rate than older children or adults. ⋯ There was no evidence of differences between methods of assay. There was a high correlation between the two glucuronide metabolites in spite of the different situations studied, supporting a single glucuronidating enzyme. Morphine was present in CSF at a fourfold higher concentration than the glucuronide metabolites.
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The analgesic effectiveness and safety of oral tramadol were compared with standard analgesics using a meta-analysis of individual patient data from randomised controlled trials in patients with moderate or severe pain after surgery or dental extraction. Calculation of %maxTOTPAR from individual patient data, and the use of > 50%maxTOTPAR defined clinically acceptable pain relief. Number-needed-to-treat (NNT) for one patient to have > 50%maxTOTPAR compared with placebo was used to examine the effectiveness of different single oral doses of tramadol and comparator drugs. ⋯ There was a dose response with tramadol, tending towards higher incidences at higher doses. Single-patient meta-analysis using more than half pain relief provides a sensitive description of the analgesic properties of a drug, and NNT calculations allow comparisons to be made with standard analgesics. Absolute ranking of analgesic performance should be done separately for postsurgical and dental pain.