Peripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy.
Milena ŚlęczkowskaRowida AlmomaniMargherita MarchiMirna AndelicBianca T A de GreefMaurice SopacuaJanneke G J HoeijmakersPatrick LindseyStephen G WaxmanGiuseppe LauriaCatharina G FaberHubert J M SmeetsMonique M GerritsPublished in: International journal of molecular sciences (2022)
Neuropathic pain is a characteristic feature of small fiber neuropathy (SFN), which in 18% of the cases is caused by genetic variants in voltage-gated sodium ion channels. In this study, we assessed the role of fifteen other ion channels in neuropathic pain. Patients with SFN (n = 414) were analyzed for ANO1 , ANO3 , HCN1 , KCNA2 , KCNA4 , KCNK18 , KCNN1 , KCNQ3 , KCNQ5 , KCNS1 , TRPA1 , TRPM8 , TRPV1 , TRPV3 and TRPV4 variants by single-molecule molecular inversion probes-next-generation sequencing. These patients did not have genetic variants in SCN3A , SCN7A-SCN11A and SCN1B-SCN4B . In twenty patients (20/414, 4.8%), a potentially pathogenic heterozygous variant was identified in an ion-channel gene (ICG). Variants were present in seven genes, for two patients (0.5%) in ANO3 , one (0.2%) in KCNK18 , two (0.5%) in KCNQ3 , seven (1.7%) in TRPA1 , three (0.7%) in TRPM8 , three (0.7%) in TRPV1 and two (0.5%) in TRPV3 . Variants in the TRP genes were the most frequent (n = 15, 3.6%), partly in patients with high mean maximal pain scores VAS = 9.65 ± 0.7 (n = 4). Patients with ICG variants reported more severe pain compared to patients without such variants (VAS = 9.36 ± 0.72 vs. VAS = 7.47 ± 2.37). This cohort study identified ICG variants in neuropathic pain in SFN, complementing previous findings of ICG variants in diabetic neuropathy. These data show that ICG variants are central in neuropathic pain of different etiologies and provides promising gene candidates for future research.
Keyphrases
- neuropathic pain
- spinal cord
- copy number
- spinal cord injury
- end stage renal disease
- ejection fraction
- newly diagnosed
- chronic kidney disease
- single molecule
- peritoneal dialysis
- genome wide
- prognostic factors
- type diabetes
- machine learning
- magnetic resonance
- gene expression
- dna methylation
- early onset
- transcription factor
- small molecule
- deep learning
- heart rate
- blood pressure
- genome wide identification
- postoperative pain
- electronic health record
- wound healing
- resistance training
- cell free