The Prevalence of Neuropathic Pain in Multiple Sclerosis-A Systematic Review and Meta-Analysis Using the NeuPSIG...

Multiple sclerosis (MS) is a neurodegenerative disorder frequently leading to neuropathic pain. Due to the neurodegenerative nature, the diagnosis of neuropathic pain remains challenging. A grading system has been developed providing an overview of diagnostic certainty (i.e., possible, probable and definite). Since no previous review has accounted for this, differences in diagnostic certainty may have affected prevalence estimates. To elucidate this issue, the current meta-analysis aimed to estimate the prevalence of possible, probable and definite neuropathic pain separately, as well as the overall prevalence of neuropathic pain in MS.

A comprehensive systematic literature review was conducted (by 14-10-2025) using PubMed, Embase and Scopus databases, adhering to the PRISMA guidelines. For the meta-analysis, we applied the Generic Inverse Variance method, using a random-effects model for proportions to compute prevalence estimates for possible, probable and definite neuropathic pain, as well as for overall prevalence.

The literature search yielded 1638 records, of which 32 papers were considered eligible for inclusion. Disregarding diagnostic certainty, the overall prevalence of neuropathic pain in people with MS was estimated at 22.3% (95% CI: 17.3; 27.3). Following stratification by diagnostic certainty, the prevalence of possible neuropathic pain was 22.0% (95% CI: 16.0; 28.0), probable neuropathic pain was 23.7% (95% CI: 19.4; 28.0), and definite neuropathic pain was 23.4% (95% CI: 1.11; 35.8).

Neuropathic pain in MS was estimated at an overall prevalence of 22.3%. Moreover, estimates of neuropathic pain in MS across diagnostic certainty levels yielded numerically similar results. However, these findings may not provide evidence of comparability; rather, they reflect methodological heterogeneity among the included studies. As such, in line with international recommendations, a diagnosis of possible neuropathic pain appears appropriate for epidemiological purposes as well as for initial screening in pwMS. However, probable and/or definite diagnoses should be adopted in clinical practice and in future studies investigating pain-phenotype-based effects in pwMS.

This review estimates the prevalence of neuropathic pain in multiple sclerosis across NeuPSIG diagnostic certainty levels, providing novel and valuable methodological insights into the application of the grading framework. Findings support the use of possible neuropathic pain for epidemiological and screening purposes, while emphasizing the importance of probable or definite diagnoses for clinical practice and pain-phenotype-based research. The review also highlights limitations of the framework and operationalization thereof that can inform future applications and refinements, particularly for central neuropathic pain, where diagnostic classification remains inherently challenging.