Pierre Blanc1, Emmanuelle Génin, Béline Jesson, Claude Dubray, Christian Dualé. 1. From the AP-HP, Génétique médicale, Hôpital Necker-Enfants Malades (PB), INSERM, UMR1163, Paris (PB), INSERM, UMR1078 (EG), CHU Brest, EFS (EG), Université de Brest, Brest (EG), HELIXIO, Groupe Hybrigenics, Saint-Beauzire (BJ), CHU Clermont-Ferrand, Centre de Pharmacologie Clinique (C. Dubray, C. Dualé), INSERM, CIC1405 & UMR1107 (C. Dubray, C. Dualé), Université Clermont Auvergne, Clermont-Ferrand, France (C. Dubray).
Abstract
BACKGROUND: Neuropathic pain following surgery could be a useful model for the study of the genetic mechanisms of peripheral neuropathic pain. OBJECTIVE: The aim of this study was to identify genetic predictors of persistent postsurgical neuropathic pain. DESIGN: An ancillary study from a prospective cohort. SETTING: Eighteen French university hospitals. PATIENTS: Five hundred and sixty-one patients at risk of persistent postoperative pain who underwent scheduled surgery were classified as 159 cases and 402 controls. INTERVENTION: Pre-operative blood sampling for DNA analysis and questionnaires sent at the third and sixth month after surgery. MAIN OUTCOME MEASURES: The phenotype was the report of pain at the site of surgery with a positive response in the DN4 questionnaire within 6 months after surgery. Out of a list of 126 candidate genes involved in the initial processes of peripheral neuropathic pain, a set of 4599 single nucleotide polymorphisms was tested on an Illumina chip. We carried out the association tests, based on an additive model, on 4422 single nucleotide polymorphisms. RESULTS: After correcting for type-I error inflation, only one suggestive association was reached for one single nucleotide polymorphism, the rs2286614, which we had selected to tag KCNK4. This gene encodes for TRAAK, a two-pore domain background K channel involved in the modulation of the primary thermoreceptors of the transient receptor potential channels family. CONCLUSION: This is the first genetic association study specifically investigating the occurrence of persistent postsurgical neuropathic pain. Its results help target future research to better understand the mechanisms of peripheral neuropathic pain. TRIAL REGISTRATION: ClinicalTrials.gov (ref. NCT00812734).
BACKGROUND:Neuropathic pain following surgery could be a useful model for the study of the genetic mechanisms of peripheral neuropathic pain. OBJECTIVE: The aim of this study was to identify genetic predictors of persistent postsurgical neuropathic pain. DESIGN: An ancillary study from a prospective cohort. SETTING: Eighteen French university hospitals. PATIENTS: Five hundred and sixty-one patients at risk of persistent postoperative pain who underwent scheduled surgery were classified as 159 cases and 402 controls. INTERVENTION: Pre-operative blood sampling for DNA analysis and questionnaires sent at the third and sixth month after surgery. MAIN OUTCOME MEASURES: The phenotype was the report of pain at the site of surgery with a positive response in the DN4 questionnaire within 6 months after surgery. Out of a list of 126 candidate genes involved in the initial processes of peripheral neuropathic pain, a set of 4599 single nucleotide polymorphisms was tested on an Illumina chip. We carried out the association tests, based on an additive model, on 4422 single nucleotide polymorphisms. RESULTS: After correcting for type-I error inflation, only one suggestive association was reached for one single nucleotide polymorphism, the rs2286614, which we had selected to tag KCNK4. This gene encodes for TRAAK, a two-pore domain background K channel involved in the modulation of the primary thermoreceptors of the transient receptor potential channels family. CONCLUSION: This is the first genetic association study specifically investigating the occurrence of persistent postsurgical neuropathic pain. Its results help target future research to better understand the mechanisms of peripheral neuropathic pain. TRIAL REGISTRATION: ClinicalTrials.gov (ref. NCT00812734).
Authors: Adam J Dourson; Adam Willits; Namrata G R Raut; Leena Kader; Erin Young; Michael P Jankowski; Vidya Chidambaran Journal: Can J Pain Date: 2022-05-10
Authors: David McCoull; Emma Ococks; Jonathan M Large; David C Tickle; Alistair Mathie; Jeffrey Jerman; Paul D Wright Journal: SLAS Discov Date: 2020-12-29 Impact factor: 3.341