HPLC-MS/MS Study Examines Relationship of Low Vitamin D to Neuropathic Pain in Spinal Cord Injury

Hypothesizing that vitamin D deficiency is highly prevalent and is associated with a higher risk of neuropathic pain (NeP) in individuals with chronic spinal cord injury (SCI), a joint study conducted by researchers from Fujian Medical University (Fuzhou, China) and The Affiliated Hospital of Putian University (Putian, China) aimed to evaluate the prevalence of vitamin D deficiency and insufficiency among this population, as well as explore the association between vitamin D levels and the presence of NeP. The vitamin D status (serum 25-hydroxyvitamin D [25(OH)D]) for patients involved in the study was measured via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A paper based on this research was published in Frontiers in Nutrition (1).

Along with sensory and motor dysfunction, SCI often involves NeP, with a reported overall point prevalence of 53% (2). According to recent data, 30–50% of individuals with SCI develop NeP within their first year following the injury, which significantly exceeds the rates of the general population (7–10%) (3,4).

A fat-soluble vitamin primarily existing as cholecalciferol (D3) and ergocalciferol (D2), vitamin D is classically recognized for regulating calcium metabolism and bone homeostasis. Emerging evidence has begun to emphasize its important (yet underappreciated) role in nervous system function and pain modulation (5-8). Previous studies have revealed that deficiencies in vitamin D substantially impacts neuropathic pain in diabetic peripheral neuropathy, cardiovascular autonomic neuropathy, post-herpetic neuralgia, and rheumatoid arthritis (9-11).

The cross-sectional study enrolled 182 adults with chronic traumatic SCI (≥ 6 months post-injury) currently admitted to two Chinese rehabilitation centers. As noted previously, vitamin D status was measured via HPLC-MS/MS. NeP was diagnosed using the Douleur Neuropathique 4 (DN4) questionnaire (score ≥ 4/10) in combination with clinical assessment by a physician. Multivariate logistic regression, controlling for confounders (such as age, comorbidity, Charlson Comorbidity Index, CCI), injury severity (American Spinal Injury Association Impairment Scale, and AIS grade), assessed the association between vitamin D levels and NeP. Receiver operating characteristic (ROC) curve analysis was performed to identify a predictive cutoff (1).

Analysis determined that the prevalence of NeP was 52.7% (96/182). Vitamin D deficiency or insufficiency [25(OH)D < 30 ng/mL] affected 64.8% (118/182) of study participants. Lower vitamin D levels were strongly and independently associated with NeP risk. Individuals in the lowest vitamin D tertile (2.00-11.68 ng/mL) had significantly higher adjusted odds of NeP compared to those in the highest tertile (16.71-23.03 ng/mL) [adjusted odds ratio: 4.8, 95% CI: (3.4, 6.8), p < 0.001]. ROC analysis identified a serum 25(OH)D level <16.35 ng/mL as a predictive cutoff for NeP (area under the curve = 0.812, sensitivity 79.1%, specificity 71.9%) (1).

“Vitamin D deficiency is highly prevalent,” the authors of the paper wrote, “and a strong, independent predictor of neuropathic pain in individuals with chronic SCI. These cross-sectional findings suggest routine screening for vitamin D deficiency might be indicated; however, interventional trials are needed to confirm a potential therapeutic role of vitamin D supplementation in managing SCI-related NeP” (1).

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References

1. Shi, T.; He, Y.; Yu, Z.; Li, J. Vitamin D Deficiency and Neuropathic Pain in Chronic Spinal Cord Injury: A Cross-Sectional Study. Front. Nutr. 2025, 12, 1706735. DOI: 10.3389/fnut.2025.1706735
2. Burke, D.; Fullen, B. M.; Stokes, D. et al.Neuropathic Pain Prevalence Following Spinal Cord Injury: A Systematic Review and Meta-Analysis. Eur. J. Pain. 2017, 21 (1), 29-44. DOI: 10.1002/ejp.905
3. Bouhassira, D.; Lantéri-Minet, M.; Attal, N. et al. Prevalence of Chronic Pain with Neuropathic Characteristics in the General Population. Pain 2008, 136 (3), 380-387. DOI: 10.1016/j.pain.2007.08.013
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7. Cui, X.; Eyles, D. W. Vitamin D and the Central Nervous System: Causative and Preventative Mechanisms in Brain Disorders. Nutrients 2022, 14 (20), 4353. DOI: 10.3390/nu14204353
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9. Yesil, H.; Sungur, U.; Akdeniz, S. et al. Association Between Serum Vitamin D Levels and Neuropathic Pain in Rheumatoid Arthritis Patients: A Cross-Sectional Study. Int. J. Rheum. Dis. 2018, 21 (2), 431-439. DOI: 10.1111/1756-185X.13160
10. Putz, Z.; Tordai, D.; Hajdú, N. et al. Vitamin D in the Prevention and Treatment of Diabetic Neuropathy. Clin. Ther. 2022, 44 (5), 813-823. DOI: 10.1016/j.clinthera.2022.03.012
11. Chao, C. T.; Chiang, C. K.; Huang, J. W. et al. Vitamin D is Closely Linked to the Clinical Courses of Herpes Zoster: From Pathogenesis to Complications. Med.Hypotheses 2015, 85 (4), 452-457. DOI: 10.1016/j.mehy.2015.06.027