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Cited by 2Multiple Sclerosis Research StudiesPain Mechanisms and TreatmentsPeripheral Neuropathies and Disorders

Neuropathic pain in multiple sclerosis: serum biomarkers and MRI lesion localization

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Ismail, Mohamed Hamdy, ELmotayam, Amal SE, Saadawy, Sara F., Elfwakhry, Rabab M., Fawzy, Hebatallah M., Sarhan, Noha T.·2025·The Egyptian Journal of Neurology, Psychiatry and Neurosurgery
DOI 10.1186/s41983-025-00955-8
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Abstract

Background: Multiple sclerosis (MS) is a chronic disease characterized by loss of central myelin, leading to various neurological impairments and frequently affecting the quality of life. A significant factor influencing the quality of life is pain, which is a personal experience and lacks a precise mathematical or manual method of quantification. Several varying factors, such as the patient's current psychological state, cognitive abilities, and environment can affect these measurements. This study aims at evaluating potential serological biomarkers of neuropathic pain in multiple sclerosis patients and correlating neuropathic pain with localization of lesions and burden of disease attributed to this symptom. This research builds upon preliminary findings presented as a poster at the 9th MENACTRIMS congress in 2024 by Sarhan et al. (Mult Scler Relat Disord 92:106003, 2024). Results: This cross-sectional study was conducted on 64 clinically definite Relapsing Remitting MS patients based on MacDonald’s criteria selected from the Zagazig University MS Outpatient Clinic. Among these patients, 40.6% reported experiencing pain as measured by The Leeds Assessment of Neuropathic Symptoms and Signs scale, while the visual analog scale indicated that 23.4 and 18.8% experienced moderate and severe pain, respectively. Interleukin-6 (IL6), Interleukin-10 (IL10), and tumor necrosis factor (TNF) levels were evaluated in our patients, revealing that these serological markers were significantly elevated in those suffering from severe and moderate pain (p < 0.001) across all applied pain assessment tools. The incidence of pain was notably higher in patients who had thalamic, brainstem, and spinal cord lesions as observed through magnetic resonance imaging (MRI). Conclusion: Neuropathic pain was highly prevalent in multiple sclerosis, Serum IL-6, IL-10 and TNF were associated with pain severity, also MRI lesion localization appeared to have association with neuropathic pain in MS, further research is warranted for more understanding of the pathophysiology of pain in multiple sclerosis and identifying the underlying biomarkers which may aid as a therapeutic target and help improving quality of life.

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  • Increased lesion load is correlated with disease duration, Expanded Disability Status Scale, and multiple sclerosis phenotypes, and is therefore expectedly positively associated with increased prevalence of neuropathic pain.

    “It has been shown that increased lesion load is correlated with disease duration, Expanded Disability Status Scale (EDSS) and MS phenotypes, and is therefore expectedly (positively) associated with increased prevalence of neuropathic pain (Ismail et al. 2025; Solaro et al. 2018; Srotova et al. 2021; Svendsen et al. 2011).”

    From The Prevalence of Neuropathic Pain in Multiple Sclerosis—A Systematic Review and Meta‐Analysis Using the <scp>NeuPSIG</scp> Algorithm (2026) · cites this paper as Ismail et al. 2025

    The Results and Table 7 (page not available in our copy) report a positive correlation between MRI lesion count and pain severity. The Introduction also links neuropathic-pain risk to longer disease duration and greater disability, but the paper does not establish that lesion load correlates with duration, EDSS, or MS phenotypes, or directly report a lesion-load correlation with pain prevalence. Its study included only relapsing-remitting MS patients. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Determining whether lesions are neuroanatomically plausible for explaining pain in multiple sclerosis is complex, as the correlation between lesion location and pain is at best moderate-to-good.

    “However, determining whether lesions are neuroanatomically plausible for explaining pain in MS is complex, as the correlation between lesion location and pain is at best moderate‐to‐good (Ismail et al. 2025; Ouyang et al. 2024; Seixas et al. 2014; Svendsen et al. 2011).”

    From The Prevalence of Neuropathic Pain in Multiple Sclerosis—A Systematic Review and Meta‐Analysis Using the <scp>NeuPSIG</scp> Algorithm (2026) · cites this paper as Ismail et al. 2025

    The Introduction and Discussion say that pain mechanisms in MS remain incompletely understood, supporting the claim that linking a lesion to pain is complex. The Results report significant associations between lesions in the thalamus, brainstem and spinal cord and pain, but do not characterize the strength of the lesion-location correlation as “at best moderate-to-good.” (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Sensitivity analysis removing lower clinical extremes for low disability, duration, and progression did not affect the conclusions, yielding 20.5% (95% CI 15.4-25.6), indicating no clear impact.

    “After removing lower clinical extremes (Aliş et al. 2025; Ismail et al. 2025; Jallouli, Ghroubi, Ben Dhia, et al. 2025), the overall sensitivity analysis for low disability, duration, and progression similarly did not affect the conclusions (20.5% [95% CI: 15.4; 25.6]), indicating no clear impact.”

    From The Prevalence of Neuropathic Pain in Multiple Sclerosis—A Systematic Review and Meta‐Analysis Using the <scp>NeuPSIG</scp> Algorithm (2026) · cites this paper as Ismail et al. 2025

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Cited by

Sorted by citations

Authors
Ismail, M. H., ELmotayam, A. S., Saadawy, S. F., Elfwakhry, R. M., Fawzy, H. M., & Sarhan, N. T.
Affiliations
Zagazig University (EG)
Corresponding author
Sarhan, Noha T.
ORCID
Venue
The Egyptian Journal of Neurology, Psychiatry and Neurosurgery
Publisher
Springer Science and Business Media LLC
Published
2025-04-10
Volume
61
Issue
1
ISSN
  • 1110-1083 (ISSN-L)
  • 1687-8329
DOI
10.1186/s41983-025-00955-8
OpenAlex
W4409332529
Cited by
2
References
4
Citations by year
2026: 2
FWCI
1.34
Type
journal article
Language
en
Open access
Licence
Locations
  • The Egyptian Journal of Neurology Psychiatry and Neurosurgery (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
Keywords
multiple sclerosis, neuropathic pain, serum biomarkers, interleukin-6, IL-10, TNF-α, MRI lesion localization, thalamic lesions, brainstem lesions, spinal cord lesions, pain intensity, relapsing-remitting multiple sclerosis, quality of life

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