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Few studies in healthy subjects have examined the neuroimmune responses associated with specific experimental pain stimuli, while none has measured multiple biomarkers simultaneously. The aim of the present study was to compare the neuro-immune responses following two common experimental pain stimuli: cold pressor test (CPT) and focal heat pain (FHP). Eight adults participated in two counterbalanced experimental sessions of FHP or CPT with continuous pain ratings and blood sampling before and 30 minutes after the sessions. Despite similar pain intensity ratings (FHP = 42.2 ± 15.3; CPT = 44.5 ± 34.1;  P  = 0.871), CPT and FHP induced different neuro-immune biomarker responses. CPT was accompanied by significant increases in cortisol ( P  = 0.046) and anti-inflammatory cytokine IL-10 ( P  = 0.043) with significant decreases in several pro-inflammatory mediators (IL-1  β   ( P  = 0.028), IL-12 ( P  = 0.012), TNF-  α   ( P  = 0.039), and MCP-1 ( P  = 0.038)). There were nonsignificant biomarker changes during the FHP session. There were close to significant differences between the sessions for IL-1  β   ( P  = 0.081), IFN-  γ   ( P  = 0.072), and IL-12 ( P  = 0.053) with biomarkers decreasing after CPT and increasing after FHP. There were stronger associations between catastrophizing and most biomarkers after CPT compared to FHP. Our results suggest that CPT is a stressful and painful stimulus, while FHP is mostly a painful stimulus. Thus, each experimental pain stimulus can activate different neuro-immune cascades, which are likely relevant for the interpretation of studies in chronic pain conditions.

Immune Biomarker Response Depends on Choice of Experimental Pain Stimulus in Healthy Adults: A Preliminary Study