Adi Shani, Michal Granot, Eilam Palzur, Mariana Agostinho, Roi Treister, Nimrod Rahamimov
Chronic pain is accompanied by widespread physiological dysregulation, yet the mucosal immune system has received little attention. Salivary secretory-immunoglobulin-A (S-IgA) is a non-invasive biomarker of mucosal immunity modulated by sustained stress and autonomic activity. This cross-sectional secondary analysis examined whether pain intensity in chronic back pain is associated with salivary S-IgA in 57 adults enrolled in a parent interventional study (NCT05994118). Pain was assessed on a computerized visual analogue scale (CoVAS, 0-100) at the laboratory visit (current pain and 24-hour average) and via a twice-daily electronic CoVAS diary (1-week, 2-week, and 14-day averages). Two saliva samples collected ∼90 minutes apart were assayed by ELISA, and baseline heart rate variability (HRV) was recorded. Spearman correlations were computed with and without partial adjustment for age, sex, and BMI; Benjamini-Hochberg correction was applied to the ten primary pain × S-IgA tests. Average 24-hour pain was negatively correlated with both S-IgA samples (ρ ≈ -.45 for both, p < .001); the 1-week (ρ ≈ -.34 to -.35, p ≤ .009) and 14-day averages (ρ ≈ -.38 for both, p = .004) showed similar associations. All average-pain associations survived FDR correction and partial adjustment. Current pain was not significantly associated with S-IgA. Baseline high-frequency HRV power was positively associated with S-IgA1 (ρ = .29, p = .033) but not S-IgA2. Sustained pain experience, rather than current pain, appears to track salivary mucosal immune function in chronic back pain. However, these hypothesis-generating findings may reflect unmeasured stress- or mood-related confounding, not a pain-specific effect.