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Observational Study
. 2026 Feb 1;167(2):455-468.
doi: 10.1097/j.pain.0000000000003822. Epub 2025 Nov 14.

Prevalence and characterization of pediatric-onset spinal cord injury pain as reported by youth: an observational and case control association study with TRPA1 gene single nucleotide polymorphisms

Marta Ríos-León  1   2   3 , Beatriz Huidobro-Labarga  4 , Inmaculada Castillo-Aguilar  5 , Antonio Segura  1   2 , Elisa López-Dolado  6 , Julian Taylor  1   2   3   7
Affiliations
Observational Study

Prevalence and characterization of pediatric-onset spinal cord injury pain as reported by youth: an observational and case control association study with TRPA1 gene single nucleotide polymorphisms

Marta Ríos-León et al. Pain. .

Abstract

Pain in pediatric-onset spinal cord injury (SCI) has an unknown prevalence and genetic basis. Cold hyperesthesia is also a key sensory sign in adults with SCI pain. This hypothesis-driven observational and genetic-phenotype study assessed transient receptor potential ankyrin 1 (TRPA1) gene single-nucleotide polymorphism (SNP) clusters rs920829, rs11988795, and rs13255063 as factors associated with pediatric-onset SCI pain. Sixty-six individuals (12.5 ± 0.1 years; 51.5% women) with pediatric-onset SCI (5.2 ± 0.1 years) were evaluated with the International SCI Pain Data Set, Child Pain Anxiety Symptoms Scale, Pain-Catastrophizing Questionnaire, dynamic quantitative sensory testing, and the home-based cold pressor test. Single-nucleotide polymorphisms were identified by melting analysis of DNA amplification with real-time fluorescence polymerase chain reaction. Spinal cord injury pain prevalence, as a cohort percentage, was 50.0% (n = 33), with both nociceptive (n = 25, 37.9%) and probable neuropathic pain (NP, n = 13, 19.7%) present. Case-control analysis revealed that the rs11988795 AG genotype was associated with increased likelihood of any pain (odds ratio [OR] 2.83, 1.02-7.91, P = 0.047), nociceptive pain (OR 3.39, 1.13-10.19, P = 0.029), and NP (OR 5.33, 1.09-25.98, P = 0.038). Both decreased (OR 0.24, 0.08-0.79, P = 0.018) and increased likelihood (OR 3.85, 1.23-12.10, P = 0.021) of musculoskeletal pain were associated with the rs11988795 GG/AG genotype, respectively. Candidate TRPA1 SNPs are also associated with cold hyperesthesia, cold pain, catastrophizing, and anxiety. Both nociceptive and NP pain were present in the cohort, with the TRPA1 rs11988795 and rs13255063 SNPs significantly associated with the likelihood of SCI pain. Further validation of TRPA1 SNPs in a larger pediatric-onset SCI cohort may advance our understanding of the underlying pathophysiology, improve prognosis, and reveal potential targets for future therapeutic exploration.

Keywords: Cold hyperesthesia; Home cold pressor test; Pain catastrophizing; Pediatric spinal cord injury; TRPA1 single-nucleotide polymorphisms.

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References

    1. Achenbach J, Rhein M, Gombert S, Meyer-Bockenkamp F, Buhck M, Eberhardt M, Leffler A, Frieling H, Karst M. Childhood traumatization is associated with differences in TRPA1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom. Clin Epigenetics 2019;11:126.
    1. Akerlund M, Baskozos G, Li W, Themistocleous AC, Pascal MMV, Rayner NW, Attal N, Baron R, Baudic S, Bennedsgaard K, Bouhassira D, Comini M, Crombez G, Faber CG, Finnerup NB, Gierthmuhlen J, Granovsky Y, Gylfadottir SS, Hebert HL, Jensen TS, John J, Kemp HI, Lauria G, Laycock H, Meng W, Nilsen KB, Palmer C, Rice ASC, Serra J, Smith BH, Tesfaye S, Topaz LS, Veluchamy A, Vollert J, Yarnitsky D, van Zuydam N, Zwart JA, McCarthy MI, Lyssenko V, Bennett DL. Genetic associations of neuropathic pain and sensory profile in a deeply phenotyped neuropathy cohort. PAIN 2024;166:1354–68.
    1. Andersen HH, Lo Vecchio S, Gazerani P, Arendt-Nielsen L. Dose-response study of topical allyl isothiocyanate (mustard oil) as a human surrogate model of pain, hyperalgesia, and neurogenic inflammation. PAIN 2017;158:1723–32.
    1. Baskozos G, Hebert HL, Pascal MM, Themistocleous AC, Macfarlane GJ, Wynick D, Bennett DL, Smith BH. Epidemiology of neuropathic pain: an analysis of prevalence and associated factors in UK Biobank. PAIN Rep 2023;8:e1066.
    1. Biering-Sorensen F, DeVivo MJ, Charlifue S, Chen Y, New PW, Noonan V, Post MWM, Vogel L. International Spinal Cord Injury Core Data Set (version 2.0)-including standardization of reporting. Spinal Cord 2017;55:759–64.

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