The association of pain with protein inflammatory biomarkers: a review of the literature.

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.

Objectives: 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.

Discussion: 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.