Abstract summary 

Adversity in childhood is robustly associated with persistent pain in adulthood. Neuro-immune interactions are a candidate mechanistic link between childhood adversity and persistent pain, given that both childhood adversity and persistent pain are associated with neural and immune upregulation in adulthood. As such, we aimed to clarify whether immune reactivity is associated with provoked differences in nociceptive processing in humans. Pain-free adults (n=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 neural provocation (high-frequency electrical stimulation) and then, separately, 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 assessed as IL-6 and TNF-α expression after 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 pro-inflammatory cytokines was not statistically associated with childhood adversity, induced secondary hyperalgesia, or vaccine-associated change in conditioned pain modulation. The current findings from a heterogenous sample cast doubt on two 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 unpack the psychoneuroimmunological mechanisms underlying vulnerability to persistent pain.

Authors & Co-authors:  Bedwell Gillian J GJ Mqadi Luyanduthando L Kamerman Peter P Hutchinson Mark R MR Parker Romy R Madden Victoria J VJ

Study Outcome 

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