Pain Research, MSk Lab, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital of Schleswig-Holstein, Kiel, Germany.
Eur J Pain. 2022 Oct;26(9):1938-1949. doi: 10.1002/ejp.2014. Epub 2022 Aug 2.
Conditioned pain modulation (CPM) and offset analgesia quantify impairment of endogenous pain modulation, but magnitude and reliability vary broadly between studies, indicating influencing factors that are not currently controlled for. The aim of this study was to quantify magnitude and retest reliability of CPM and offset analgesia in healthy participants, while investigating the influence of sex and sex hormone levels.
Sixty-two participants (30 female) completed the study. We tested CPM (heat-cold paradigm) and offset analgesia on 6 days within two menstrual cycles (tests were performed in each phase of two subsequent menstrual cycles, with similar time points for men).
Median offset effect was -29.4% in female and - 22.5% in male participants (as change from initial stimulus). Median early CPM effects were - 16.7% for women versus -13.3% for men. Reliability (intra-class correlation coefficient [ICC]) was similar between the main measures, offset effect (female: 0.48, male: 0.47) and early CPM effect (female: 0.49, male: 0.43). There was significant variance between individual experimental parameters within protocols but not between sexes or menstrual phases. While oestradiol and progesterone did not correlate with the magnitude of effect within sexes, we found that testosterone levels explained an estimated 5%-10% of variance within individual responses in all sexes.
Our results show that the reliability of both CPM effect and offset analgesia was independent of sex and menstrual cycle phase. The magnitude of CPM and offset effects was weakly influenced by sex and testosterone levels, indicating an area for future research, rather than clinical significance.
This study investigated CPM and offset analgesia in parallel, across sexes and during two menstrual cycles while assessing the impact of sex hormones. Reliability seems to depend on experimental parameters rather than participant characteristics, while the magnitude of effect could be weakly linked to sex hormones and sex.
条件性疼痛调制（CPM）和偏移镇痛定量内源性疼痛调制的损伤，但幅度和可靠性在研究之间差异很大，表明目前未控制的影响因素。本研究的目的是量化健康参与者的 CPM 和偏移镇痛的幅度和复测可靠性，同时研究性别和性激素水平的影响。
62 名参与者（30 名女性）完成了这项研究。我们在两个月经周期内的 6 天内测试了 CPM（冷热范式）和偏移镇痛（在随后的两个月经周期的每个阶段进行测试，对于男性来说，时间点相似）。
女性的中位偏移效应为-29.4%，男性为-22.5%（作为初始刺激的变化）。女性的早期 CPM 效应中位数为-16.7%，男性为-13.3%。主要测量指标（女性：0.48，男性：0.47）和早期 CPM 效应（女性：0.49，男性：0.43）的可靠性（组内相关系数[ICC]）相似。尽管在方案内个别实验参数之间存在显著差异，但性别或月经周期阶段之间没有差异。虽然雌二醇和孕酮与性别内效应的幅度没有相关性，但我们发现，在所有性别中，睾丸激素水平解释了个体反应中约 5%-10%的方差。
我们的结果表明，CPM 效应和偏移镇痛的可靠性与性别和月经周期阶段无关。CPM 和偏移效应的幅度受性别和睾丸激素水平的微弱影响，表明这是未来研究的一个领域，而不是临床意义。
本研究平行研究了 CPM 和偏移镇痛，跨性别，并在两个月经周期期间，同时评估了性激素的影响。可靠性似乎取决于实验参数，而不是参与者特征，而效应幅度可能与性激素和性别有微弱联系。
