Conditioned pain modulation identifies altered sensitivity in extremely preterm young adult males and females

• Published in: British journal of anaesthesia : BJA Vol. 121; no. 3; pp. 636 - 646
• Main Authors: Walker, S.M., O'Reilly, H., Beckmann, J., Marlow, N.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2018; Elsevier
• Subjects: Analgesics - administration & dosage; conditioned pain modulation; Conditioning, Psychological - physiology; Drug Utilization - statistics & numerical data; extremely premature; Female; Humans; infant; Infant, Extremely Premature - psychology; Infant, Newborn; Ireland - epidemiology; Longitudinal Studies; Male; Pain; Pain - epidemiology; Pain - psychology; Pain Measurement - methods; Pain Perception - physiology; Pain Threshold - physiology; United Kingdom - epidemiology; Young Adult; United Kingdom; Ireland; pain; infant; conditioned pain modulation; extremely premature
• ISSN: 0007-0912; 1471-6771; 1471-6771
• DOI: 10.1016/j.bja.2018.05.066

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.