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

Natalia Drobinska; Egle Sukockiene; Marjolaine Uginet; Patrice H Lalive; Agustina M Lascano

doi:10.1016/j.msard.2026.107249

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

Mult Scler Relat Disord. 2026 Aug:112:107249. doi: 10.1016/j.msard.2026.107249. Epub 2026 May 13.

Authors

Natalia Drobinska¹, Egle Sukockiene¹, Marjolaine Uginet¹, Patrice H Lalive¹, Agustina M Lascano²

Affiliations

¹ Department of Clinical Neurosciences, Division of Neurology, Geneva University Hospitals and University of Geneva, Switzerland.
² Department of Clinical Neurosciences, Division of Neurology, Geneva University Hospitals and University of Geneva, Switzerland. Electronic address: Agustina.Lascano@hug.ch.

PMID: 42263353
DOI: 10.1016/j.msard.2026.107249

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Evoked potentials; Magnetic resonance imaging; Neuroinflammation; Neuropathic pain; Nociceptive pain.

MeSH terms

Adult
Evoked Potentials, Somatosensory* / physiology
Female
Humans
Laser-Evoked Potentials
Male
Middle Aged
Multiple Sclerosis* / complications
Multiple Sclerosis* / diagnosis
Multiple Sclerosis* / physiopathology
Neuralgia* / diagnosis
Neuralgia* / etiology
Neuralgia* / physiopathology
Pain Measurement*