title: The brain-derived neurotrophic factor pathway, life stress, and chronic multi-site musculoskeletal pain.
abstract: BACKGROUND
  Brain-derived neurotrophic factor (BDNF) disturbances and life stress, both independently and in interaction, have been hypothesized to induce chronic pain. We examined whether (a) the BDNF pathway (val(66)met genotype, gene expression, and serum levels), (b) early and recent life stress, and (c) their interaction are associated with the presence and severity of chronic multi-site musculoskeletal pain.
  
  
  METHODS
  Cross-sectional data are from 1646 subjects of the Netherlands Study of Depression and Anxiety. The presence and severity of chronic multi-site musculoskeletal pain were determined using the Chronic Pain Grade (CPG) questionnaire. The BDNF val(66)met polymorphism, BDNF gene expression, and BDNF serum levels were measured. Early life stress before the age of 16 was assessed by calculating a childhood trauma index using the Childhood Trauma Interview. Recent life stress was assessed as the number of recent adverse life events using the List of Threatening Events Questionnaire.
  
  
  RESULTS
  Compared to val(66)val, BDNF met carriers more often had chronic pain, whereas no differences were found for BDNF gene expression and serum levels. Higher levels of early and recent stress were both associated with the presence and severity of chronic pain (p < 0.001). No interaction effect was found for the BDNF pathway with life stress in the associations with chronic pain presence and severity.
  
  
  CONCLUSIONS
  This study suggests that the BDNF gene marks vulnerability for chronic pain. Although life stress did not alter the impact of BDNF on chronic pain, it seems an independent factor in the onset and persistence of chronic pain.
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands e.generaal@ggzingeest.nl.
authors.forename: Ellen
authors.initials: E
authors.lastname: Generaal
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Milaneschi
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: Jansen
authors.affiliation: Institute of Psychology, Leiden University, Leiden, The Netherlands Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
authors.forename: Bernet M
authors.initials: BM
authors.lastname: Elzinga
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands Department of Rehabilitation Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Dekker
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D059350:Chronic Pain / Q000378:metabolism* / Q000523:psychology*; D005260:Female; D006801:Humans; D008297:Male; D059352:Musculoskeletal Pain / Q000378:metabolism* / Q000523:psychology*; D012720:Severity of Illness Index; D015398:Signal Transduction; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: Chronic pain; child abuse; life change events; nerve growth factors