title: The association of pain with protein inflammatory biomarkers: a review of the literature.
abstract: BACKGROUND
  Pain is a key diagnostic criterion in many medical conditions. In the absence of self-reported pain, measurement of a proxy for pain, such as an inflammatory biomarker, could aid in diagnosis and disease management.
  
  
  OBJECTIVE
  The aim was to determine if there is an association between inflammatory biomarkers and self-reported pain in individuals with medical conditions associated with the symptom of pain and to clarify whether inflammatory biomarkers might aid in the diagnostic process.
  
  
  METHODS
  An integrative literature review was conducted. PubMed, CINAHL, and Cochrane databases were searched for articles published between January 2000 and September 2012. Inclusion criteria were original research testing a relationship between inflammatory biomarkers and pain, pain measurement, laboratory measure of inflammatory biomarkers, and a prospective single-group experimental design or comparative nonrandomized or randomized design. Excluded were studies describing an association between inflammatory biomarkers and treatment, risk, and generation; pathophysiology; or genetic polymorphisms/transcripts. Ten studies meeting inclusion criteria were reviewed.
  
  
  RESULTS
  In most of the studies, baseline elevations in both proinflammatory and anti-inflammatory cytokines were reported in painful conditions compared with healthy controls. In half of the studies, higher levels of proinflammatory markers (C-reactive protein, tumor necrosis factor-alpha, interleukin-2 [IL-2], IL-6, IL-8, IL-10, and CD40 ligand) were associated with greater pain. Proinflammatory cytokines decreased after treatment for pain in only two studies.
  
  
  CONCLUSIONS
  The association between inflammatory markers varied in the direction and magnitude of expression, which may be explained by differences in designs and assays, disease condition and duration, variations in symptom severity, and timing of measurement. Elevation in anti-inflammatory cytokines in the presence of pain represents a homeostatic immune response. Further study is required to determine the value of cytokines as biomarkers of pain.
authors: Holli A. DeVon, PhD, RN, is Associate Professor; and Mariann R. Piano, PhD, RN, is Professor, College of Nursing, University of Illinois at Chicago. Anne G. Rosenfeld, PhD, RN, FAAN, FAHA, is Professor and Associate Dean, College of Nursing, University of Arizona, Tucson. Debra A. Hoppensteadt, PhD, MT (ASCP), is Professor, School of Medicine, Loyola University Chicago, Illinois.
authors: Holli A
authors: HA
authors: DeVon
authors: Mariann R
authors: MR
authors: Piano
authors: Anne G
authors: AG
authors: Rosenfeld
authors: Debra A
authors: DA
authors: Hoppensteadt
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000175:diagnosis* / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods*; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D016207:Cytokines