Mapping the neuropathic-sensory-affective pain axis in Sjögren's disease toward neuropsychological phenotyping

BACKGROUND: Pain is one of the most disabling manifestations of Sjögren's disease (SjD). Whether neuropathic descriptors, sensory abnormalities and depressive symptoms represent distinct or integrated dimensions of the SjD phenotype is unknown. OBJECTIVES: To characterize the prevalence, correlates and clinical relevance of neuropathic pain symptoms and bedside sensory abnormalities in SjD, and to explore how sensory dysfunction and affective burden jointly shape the clinical expression of pain. METHODS: In this cross-sectional study, 114 SjD patients underwent comprehensive assessment including the Neuropathic Pain Symptom Inventory (NPSI), LANSS-derived bedside sensory testing, Patient Health Questionnaire-9 (PHQ-9), Visual Analogue Scale (VAS) pain/fatigue, EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). A data-driven unsupervised Gaussian mixture modelling approach was used to define a NPSI transition cut-off. Predictors of NPSI≥15 were analysed using logistic regression. Unsupervised clustering was applied to identify latent pain-sensory-mood phenotypes. RESULTS: Neuropathic symptoms were common: 79.8% reported ≥1 NPSI descriptor across all five domains, and sensory abnormalities occurred in 80%. An unsupervised, distribution-based approach identified NPSI≥15 as a transition point. Patients with NPSI≥15 had higher pain, fatigue, sicca, and depressive symptoms despite similar ESSDAI. In multivariable penalised regression, PHQ-9 (OR 1.36, p < 0.001) and fatigue (OR 1.03, p = 0.013) were independently associated with high NPSI, whereas widespread pain was borderline (OR 3.35, p = 0.052) and female sex showed a protective trend. Unsupervised clustering identified latent pain-sensory-mood phenotypes, including a high-burden subgroup with elevated NPSI and prominent affective and fatigue features. CONCLUSION: Our findings highlight the relevance of a neuropathic pain-sensory-affective axis in SjD, suggesting the need of a neuropsychological reframing of the disease toward a precision phenotyping.