• Yuanyuan Tian, Xiaodong Liu, Mingzhong Jia, Hui Yu, Peter Lichtner, Yujian Shi, Zhaoyu Meng, Shanglong Kou, Ho Idy H T IHT, Bo Jia, Cheng Benny C P BCP, Lam Carmen K M CKM, Sharon Tsang, Sunny H Wong, Jun Yu, Cheng Christopher H K CHK, Tony Gin, Wu William K K WKK, Zheyu Chen, Chan Matthew T V MTV, and Persistent Pain after Surgery Study Investigators.
• From the Department of Anaesthesia and Intensive Care (Y.T., X.L., Z.M., S.K., I.H.T.H., B.J., S.T., T.G., W.K.K.W., M.T.V.C.), Li Ka Shing Institute of Health Sciences (Y.T., X.L., S.K., I.H.T.H., B.J., S.T., S.H.W., J.Y., W.K.K.W., M.T.V.C.), School of Biomedical Sciences (Y.S., C.H.K.C.), and Department of Medicine and Therapeutics (S.H.W., J.Y., W.K.K.W.), Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; the Shandong Provincial Key Laboratory of Mental Disorders, Department of Neurobiology, School of Medicine, Shandong University, Jinan, Shandong, China (M.J., H.Y., Z.C.); the Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (P.L); and the Department of Anaesthesia and Intensive Care, Tuen Mun Hospital, Hong Kong Special Administrative Region, China (B.C.P.C., C.K.M.L.).
• Anesthesiology. 2018 Mar 1; 128 (3): 587-597.

BackgroundThe purpose of this study was to evaluate the association between single-nucleotide polymorphisms and chronic postsurgical pain.MethodsUsing 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.ResultsAt 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 mice compared with BDNF group after plantar incision.ConclusionsThis study demonstrated that genetic variant of BDNF rs6265G>A is associated with decreased risk of chronic postsurgical pain.

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