Inflammatory reactivity is unrelated to childhood adversity or provoked modulation of nociception

Date

2025

Authors

Bedwell, G.J.
Mqadi, L.
Kamerman, P.
Hutchinson, M.R.
Parker, R.
Madden, V.J.

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Journal article

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Pain, 2025; 166(1):e590-e605

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Gillian J. Bedwell, Luyanduthando Mqadi, Peter Kamerman, Mark R. Hutchinson, Romy Parker, Victoria J. Madden

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Abstract

Adversity in childhood elevates the risk of persistent pain in adulthood. Neuroimmune interactions are a candidate mechanistic link between childhood adversity and persistent pain.We aimed to clarifywhether immune reactivity is associated with provoked differences in nociceptive processing in adults with a range of childhood adversity. Pain-free adults (n5 96; 61 female; median [range] age: 23 [18-65] years old) with a history of mild to severe childhood adversity underwent psychophysical assessments before and after in vivo neural provocation (high-frequency electrical stimulation) and, separately, before and after in vivo immune provocation (influenza vaccine administration). Psychophysical assessments included the surface area of secondary hyperalgesia after neural provocation and change in conditioned pain modulation (test stimulus: pressure pain threshold; conditioning stimulus: cold water immersion) after immune provocation. Immune reactivity was operationalised as interleukin-6 and tumour necrosis factor-a expression after in vitro lipopolysaccharide provocation of whole blood. We hypothesised associations between immune reactivity and (1) childhood adversity, (2) induced secondary hyperalgesia, and (3) vaccine-associated change in conditioned pain modulation. We found that provoked expression of proinflammatory cytokines was not statistically associated with childhood adversity, induced secondary hyperalgesia, or vaccine-associated change in conditioned painmodulation. The current findings from a heterogenous sample cast doubt on 2 prominent ideas: that childhood adversity primes the inflammatory system for hyper-responsiveness in adulthood and that nociceptive reactivity is linked to inflammatory reactivity. This calls for the broader inclusion of heterogeneous samples in fundamental research to investigate the psychoneuroimmunological mechanisms underlying vulnerability to persistent pain.

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Research Paper

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© 2025 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.

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