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

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.