Average pain over time, but not current pain, is associated with salivary secretory immunoglobulin a in chronic back pain: A cross-sectional study
Mol Pain. 2026 Jan-Dec;22:17448069261483479. doi: 10.1177/17448069261483479. Epub 2026 Aug 24.
ABSTRACT
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.
PMID:42635010 | DOI:10.1177/17448069261483479