Newly Published
Pain Medicine  |   December 2017
Targeted Genotyping Identifies Susceptibility Locus in Brain-derived Neurotrophic Factor Gene for Chronic Postsurgical Pain
Author Notes
  • 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.).
  • Prince of Wales Hospital, Hong Kong Special Administrative Region.
  • Prince of Wales Hospital, Hong Kong Special Administrative Region.
  • Prince of Wales Hospital, Hong Kong Special Administrative Region.
  • Prince of Wales Hospital, Hong Kong Special Administrative Region.
  • Prince of Wales Hospital, Hong Kong Special Administrative Region.
  • Prince of Wales Hospital, Hong Kong Special Administrative Region.
  • Prince of Wales Hospital, Hong Kong Special Administrative Region.
  • Prince of Wales Hospital, Hong Kong Special Administrative Region.
  • Tuen Mun Hospital
  • Tuen Mun Hospital
  • The Chinese University of Hong Kong.
  • T.G., W.K.K.W., Z.C., and M.T.V.C. contributed equally to this article.
    T.G., W.K.K.W., Z.C., and M.T.V.C. contributed equally to this article.×
  • *Members of Persistent Pain after Surgery Study Group are listed in the appendix.
    Members of Persistent Pain after Surgery Study Group are listed in the appendix.×
  • Submitted for publication April 10, 2017. Accepted for publication October 11, 2017.
    Submitted for publication April 10, 2017. Accepted for publication October 11, 2017.×
  • Acknowledgments: This study was coordinated by the Department of Anesthesia and Intensive Care, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
    Acknowledgments: This study was coordinated by the Department of Anesthesia and Intensive Care, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.×
  • Research Support: Supported by project grant No. 464212 from the General Research Fund, Research Grant Council (Hong Kong Special Administrative Region, China); project grant No. 11121051 from the Health and Medical Research Fund (Hong Kong Special Administrative Region, China); and project grant No. LTP001/14 and academic enhancement grant No. AEG13/001 from the Anesthesia and Pain Medicine Foundation, Australian and New Zealand College of Anaesthetists (Melbourne, Victoria, Australia).
    Research Support: Supported by project grant No. 464212 from the General Research Fund, Research Grant Council (Hong Kong Special Administrative Region, China); project grant No. 11121051 from the Health and Medical Research Fund (Hong Kong Special Administrative Region, China); and project grant No. LTP001/14 and academic enhancement grant No. AEG13/001 from the Anesthesia and Pain Medicine Foundation, Australian and New Zealand College of Anaesthetists (Melbourne, Victoria, Australia).×
  • Competing Interests: The authors declare no competing interests.
    Competing Interests: The authors declare no competing interests.×
  • Correspondence: Address correspondence to Dr. Chan: Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China. mtvchan@cuhk.edu.hk. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Pain Medicine
Pain Medicine   |   December 2017
Targeted Genotyping Identifies Susceptibility Locus in Brain-derived Neurotrophic Factor Gene for Chronic Postsurgical Pain
Anesthesiology Newly Published on December 14, 2017. doi:10.1097/ALN.0000000000001977
Anesthesiology Newly Published on December 14, 2017. doi:10.1097/ALN.0000000000001977
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 BDNFMet/Met mice compared with BDNFVal/Val group after plantar incision.

Conclusions: This study demonstrated that genetic variation of BDNF is associated with an increased risk of chronic postsurgical pain.