title: Pneumogastric (Vagus) Nerve Activity Indexed by Heart Rate Variability in Chronic Pain Patients Compared to Healthy Controls: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  A large body of scientific literature derived from experimental studies emphasizes the vital role of vagal-nociceptive networks in acute pain processing. However, research on vagal activity, indexed by vagally-mediated heart rate variability (vmHRV) in chronic pain patients (CPPs), has not yet been summarized.
  
  
  OBJECTIVE
  To systematically investigate differences in vagus nerve activity indexed by time- and frequency-domain measures of vmHRV in CPPs compared to healthy controls (HCs).
  
  
  METHODS
  A systematic review and meta-analysis, including meta-regression on a variety of populations (i.e., clinical etiology) and study-level (i.e., length of HRV recording) covariates.
  
  
  METHODS
  Not applicable (variety of studies included in the meta-analysis).
  
  
  METHODS
  Eight computerized databases (PubMed via MEDLINE, PsycNET, PsycINFO, Embase, CINAHL, Web of Science, PSYNDEX, and the Cochrane Library) in addition to a hand search were systematically screened for eligible studies based on pre-defined inclusion criteria. A meta-analysis on all empirical investigations reporting short- and long-term recordings of continuous time- (root-mean-square of successive R-R-interval differences [RMSSD]) and frequency-domain measures (high-frequency [HF] HRV) of vmHRV in CPPs and HCs was performed. True effect estimates as adjusted standardized mean differences (SMD; Hedges g) combined with inverse variance weights using a random effects model were computed.
  
  
  RESULTS
  CPPs show lower vmHRV than HCs indexed by RMSSD (Z = 5.47, P < .0001; g = -0.24;95% CI [-0.33, -0.16]; k = 25) and HF (Z = 4.54, P < .0001; g = -0.30; 95% CI [-0.44, -0.17]; k = 61).Meta-regression on covariates revealed significant differences by clinical etiology, age, gender, and length of HRV recording.
  
  
  CONCLUSIONS
  We did not control for other potential covariates (i.e., duration of chronic pain, medication intake) which may carry potential risk of bias.
  
  
  CONCLUSIONS
  The present meta-analysis is the most extensive review of the current evidence on vagal activity indexed by vmHRV in CPPs. CPPs were shown to have lower vagal activity, indexed by vmHRV, compared to HCs. Several covariates in this relationship have been identified. Further research is needed to investigate vagal activity in CPPs, in particular prospective and longitudinal follow-up studies are encouraged.
authors.affiliation: Department of Psychology, Ohio State University, Columbus, OH.
authors.forename: Julian
authors.initials: J
authors.lastname: Koenig
authors.affiliation: School of Therapeutic Sciences, SRH University Heidelberg, Heidelberg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Falvay
authors.affiliation: Department of Clinical Psychology and Psychotherapy, University of Hamburg, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Clamor
authors.affiliation: Department of Psychology, University of Marburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Wagner
authors.affiliation: Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Marc N
authors.initials: MN
authors.lastname: Jarczok
authors.affiliation: School of Computing, National University of Singapore.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ellis
authors.affiliation: Medical Department, Division of Psychosomatic Medicine, Charite, Berlin, Germany.
authors.forename: Cora
authors.initials: C
authors.lastname: Weber
authors.affiliation: Department of Psychology, Ohio State University, Columbus, OH.
authors.forename: Julian F
authors.initials: JF
authors.lastname: Thayer
mesh_terms: D000328:Adult; D000368:Aged; D059350:Chronic Pain / Q000175:diagnosis* / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D014630:Vagus Nerve / Q000502:physiology* / Q000503:physiopathology*