Targeted Genotyping Identifies Susceptibility Locus in Brain-derived Neurotrophic Factor Gene for Chronic Postsurgical Pain. (March 2018)

• Record Type: Journal Article
• Authors: Tian, Yuanyuan; Liu, Xiaodong; Jia, Mingzhong; Yu, Hui; Lichtner, Peter; Shi, Yujian; Meng, Zhaoyu; Kou, Shanglong; Ho, Idy H. T.; Jia, Bo; Cheng, Benny C. P.; Lam, Carmen K. M.; Tsang, Sharon; Wong, Sunny H.; Yu, Jun; Cheng, Christopher H. K.; Gin, Tony; Wu, William K. K.; Chen, Zheyu; Chan, Matthew T. V.
• Is Part Of: Anesthesiology. Volume 128:Number 3(2018)
• Publication Date: 2018-03
• Subjects: Anesthesiology -- Periodicals; Anesthetics -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1097/ALN.0000000000001977
• Languages: English
• ISSNs: 0003-3022

Abstract

Abstract : Background: The purpose of this study was to evaluate the association between single-nucleotide polymorphisms and chronic postsurgical pain. Methods: Using GoldenGate genotyping assays, we genotyped 638 polymorphisms within 54 pain-related genes in 1, 152 surgical patients who were enrolled in our Persistent Pain after Surgery Study. Patients were contacted by phone to determine whether they had chronic postsurgical pain at 12 months. Polymorphisms identified were validated in a matched cohort of 103 patients with chronic postsurgical pain and 103 patients who were pain free. The functions of targeted polymorphisms were tested in an experimental plantar incisional nociception model using knock-in mice. Results: At 12 months after surgery, 246 (21.4%) patients reported chronic postsurgical pain. Forty-two polymorphisms were found to be associated with chronic postsurgical pain, 19 decreased the risk of pain, and 23 increased the risk of pain. Patients carrying allele A of rs6265 polymorphism in brain-derived neurotrophic factor (BDNF) had a lower risk of chronic postsurgical pain in the discovery and validation cohorts, with an adjusted odds ratio (95% CI) of 0.62 (0.43 to 0.90) and 0.57 (0.39 to 0.85), respectively. Age less than 65 yr, male sex, and prior history of pain syndrome were associated with an increased risk of pain. Genetic polymorphisms had higher population attributable risk (7.36 to 11.7%) compared with clinical risk factors (2.90 to 5.93%). Importantly, rs6265 is a substitution of valine by methionine at amino acid residue 66 (Val66Met) and was associated with less mechanical allodynia in BDNF Met/Met mice compared with BDNF Val/Val group after plantar incision. Conclusions: This study demonstrated that genetic variant of BDNF rs6265G>A is associated with decreased risk of chronic postsurgical pain. Abstract : Among more than 1, 000 surgical patients, 21% reported chronic postsurgical pain 12 months after surgery. Patients were genotyped for 638 single nucleotide polymorphisms in 54 pain-related genes, with 23 and 19 polymorphisms associated with increased and decreased pain, respectively, including a polymorphism in brain-derived neurotrophic factor associated with lower risk. Mice with the brain-derived neurotrophic factor polymorphism had less nociceptive response to a surgical incision compared with wild-type animals.Supplemental Digital Content is available in the text.