Neuropathic pain in multiple sclerosis: discrepancies between DN4 screening and neurophysiological measures

Pain is a common and disabling symptom in multiple sclerosis (MS), yet its pathophysiological mechanisms remain poorly understood. Clinical assessment of neuropathic pain relies largely on subjective screening tools such as the DN4 questionnaire. This study aimed to characterize pain phenotype in MS using the DN4 score and to determine its relationship with objective neurophysiological markers of nociceptive and non-nociceptive pathway function assessed by laser-evoked (LEPs) and somatosensory evoked potentials (SEPs).

Fifty MS patients reporting pain underwent standardized clinical evaluation, including DN4, pain intensity (VAS), fatigue (FSMC), anxiety and depression (HADS), and disability (EDSS). LEPs were recorded after laser stimulation of the hand and foot dorsum, and SEPs following median and tibial nerve stimulation. Neurophysiological parameters were compared between patients with DN4 <4 and ≥4. Logistic regression, non-parametric group comparisons, and correlation analyses were performed.

Neuropathic pain phenotype (DN4 ≥4) was identified in 56% of patients. DN4 showed moderate correlation with pain intensity and fatigue, and weakly with anxiety, but showed no significant association with LEPs or SEPs. Logistic regression confirmed that no neurophysiological measure independently predicted DN4 ≥4 status. LEP and SEP abnormalities were not significantly correlated, suggesting dissociated involvement of nociceptive and large-fiber pathways.

In MS, DN4-defined pain phenotype reflects subjective symptom burden rather than objective sensory pathway dysfunction. Its limited correlation with neurophysiological measures highlights pain's multidimensional nature in MS. LEPs and SEPs provide complementary mechanistic insights, supporting a multimodal, mechanism-oriented approach to pain assessment and management.