Clinical Neurosciences (Pain Research), UCL Great Ormond Street Institute of Child Health, London, UK; Department of Anaesthesia and Pain Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Academic Neonatology, UCL EGA Institute for Women's Health, London, UK.
Br J Anaesth. 2018 Sep;121(3):636-646. doi: 10.1016/j.bja.2018.05.066. Epub 2018 Jul 6.
Conditioned pain modulation is a potential biomarker for risk of persistent pain. As early-life experience can alter subsequent somatosensory processing and pain response, we evaluated conditioned pain modulation after extremely preterm birth.
This observational study recruited extremely preterm (<26 weeks gestation; n=98) and term-born control (n=48) young adults (19-20 yr) from the longitudinal EPICure cohort. Pressure pain threshold (PPT; variable test stimulus lower leg) was measured before, during, and after a conditioning stimulus (contralateral hand immersion; 5°C water; 30 s). Questionnaires assessed current pain, medication use, anxiety, and pain catastrophising.
For participants tolerating conditioning, there were significant main effects of extremely preterm status, sex, and time on PPT during and after hand immersion. Inhibitory modulation was evoked in 64/98 extremely preterm (3, no change) and 38/48 term-born control (3, facilitation) subjects. The conditioned pain modulation effect (percentage change in PPT) did not differ between the extremely preterm and term-born control groups {53% [95% confidence interval (CI): 41-65] vs 57% [95% CI: 42-71]}. Reduced cold tolerance (<20 s) hampered conditioned pain modulation quantification in a higher proportion of extremely preterm participants [extremely preterm vs term-born control: 31/98 (32%) vs 7/48 (15%); P=0.03]. One-third of extremely preterm females withdrew the hand before parallel PPT (<15 s), and had lower baseline PPT than term-born control females [4.9 (95% CI: 4.8-5.1) vs 5.3 (95% CI: 5.1-5.5) ln kPa; P=0.02]. Higher anxiety, pain catastrophising, and medication use correlated with pain intensity, but not conditioned pain modulation effect.
Cold conditioning evoked inhibitory modulation in the majority of young adults and identified a subgroup of extremely preterm females with increased baseline sensitivity. Early-life experience and sex/gender should be considered when evaluating persistent pain risk with conditioned pain modulation.
条件性疼痛调制是持续性疼痛风险的潜在生物标志物。由于早期经历会改变后续的躯体感觉处理和疼痛反应，我们评估了极低出生体重早产儿出生后的条件性疼痛调制。
这项观察性研究招募了来自纵向 EPICure 队列的极低出生体重早产儿（<26 周妊娠；n=98）和足月出生对照组（n=48）的年轻成年人（19-20 岁）。在条件刺激（对侧手部浸入 5°C 水中 30 秒）之前、期间和之后测量压力疼痛阈值（PPT；变量测试刺激小腿）。问卷调查评估了当前疼痛、药物使用、焦虑和疼痛灾难化。
对于能够耐受条件刺激的参与者，在手部浸入时和之后，极低出生体重早产儿的状态、性别和时间对 PPT 有显著的主要影响。在 98 名极低出生体重早产儿中有 64 名（3 名，无变化）和 48 名足月出生对照组中有 38 名（3 名，促进）参与者出现了抑制性调制。极低出生体重早产儿和足月出生对照组之间的条件疼痛调制效应（PPT 百分比变化）没有差异{53% [95%置信区间（CI）：41-65] vs 57% [95% CI：42-71]}。极低出生体重组中，较低的冷耐受能力（<20 秒）使更多的参与者无法进行条件疼痛调制定量评估[极低出生体重组与足月出生对照组：31/98（32%）与 7/48（15%）；P=0.03]。三分之一的极低出生体重女性在平行 PPT 之前（<15 秒）撤回了手，并且比足月出生对照组女性的基线 PPT 低[4.9（95% CI：4.8-5.1）与 5.3（95% CI：5.1-5.5）ln kPa；P=0.02]。较高的焦虑、疼痛灾难化和药物使用与疼痛强度相关，但与条件疼痛调制效应无关。
低温条件刺激在大多数年轻成年人中诱发了抑制性调制，并确定了一组极低出生体重女性，其基线敏感性增加。在评估条件性疼痛调制的持续性疼痛风险时，应考虑早期生活经历和性别/性别。
