{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:10:34Z","timestamp":1768569034808,"version":"3.49.0"},"posted":{"date-parts":[[2024,12,16]]},"group-title":"Pain Medicine","reference-count":76,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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 clarify whether immune reactivity is associated with provoked differences in nociceptive processing in adults with a range of childhood adversity. 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\n                  <jats:italic>in vivo<\/jats:italic>\n                  neural provocation (high-frequency electrical stimulation) and, separately, before and after\n                  <jats:italic>in vivo<\/jats:italic>\n                  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 IL-6 and TNF-\u03b1 expression after\n                  <jats:italic>in vitro<\/jats:italic>\n                  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 investigate the psychoneuroimmunological mechanisms underlying vulnerability to persistent pain.\n                <\/jats:p>","DOI":"10.1101\/2024.12.16.24319079","type":"posted-content","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T16:30:12Z","timestamp":1734539412000},"source":"Crossref","is-referenced-by-count":1,"title":["Inflammatory reactivity is unrelated to childhood adversity or provoked modulation of nociception"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4522-5679","authenticated-orcid":false,"given":"Gillian J","family":"Bedwell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0542-2221","authenticated-orcid":false,"given":"Luyanduthando","family":"Mqadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3103-5295","authenticated-orcid":false,"given":"Peter","family":"Kamerman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2154-5950","authenticated-orcid":false,"given":"Mark R","family":"Hutchinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4823-2487","authenticated-orcid":false,"given":"Romy","family":"Parker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5357-4062","authenticated-orcid":false,"given":"Victoria J","family":"Madden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025040406350628000_2024.12.16.24319079v3.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msksp.2021.102400"},{"key":"2025040406350628000_2024.12.16.24319079v3.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chiabu.2023.106353"},{"key":"2025040406350628000_2024.12.16.24319079v3.3","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2015.67"},{"key":"2025040406350628000_2024.12.16.24319079v3.4","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.13512"},{"key":"2025040406350628000_2024.12.16.24319079v3.5","unstructured":"Bernstein, D.P. , L. 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