S. Farrell1,2, R. de Zoete1,3, P. Cabot4, M. Sterling1
1The University of Queensland, Recover Injury Research Centre, Brisbane, Australia, 2Griffith University, Menzies Health Institute Queensland, Gold Coast, Australia, 3The University of Adelaide, School of Allied Health Science and Practice, Adelaide, Australia, 4The University of Queensland, School of Pharmacy, Brisbane, Australia
Background: Pathophysiology underpinning pain and disability in non-specific neck pain (NSNP) and whiplash-associated disorder (WAD) is not well understood. There are emerging observations of systemic inflammation in musculoskeletal spinal pain which could have clinical significance.
Purpose: This systematic review investigated whether: i) blood inflammatory markers are raised in neck pain; and ii) blood inflammatory markers are associated with clinical outcomes such as pain, disability, or psychological variables.
Methods: Databases (EMBASE, MEDLINE, Cochrane, CINAHL, Web of Science) were searched for studies reporting blood inflammatory markers in adults with NSNP or WAD. Two independent reviewers screened studies for inclusion and extracted data on demographics, clinical outcomes and inflammatory marker concentrations. When sufficient data were available to be pooled, random-effects meta-analysis was undertaken to determine standard mean differences (SMDs). Best evidence synthesis was used when meta-analysis was not possible. The Newcastle Ottawa Scale was used to assess risk of bias of individual studies, while overall quality of evidence from meta-analysis was determined by the Grades of Recommendation, Assessment, Development, and Evaluation approach.
Results: After screening (2,403 records as titles and abstracts, 38 records as full-texts), ten studies comprising 706 participants were included in the review. Three studies provided data on acute WAD, two on chronic WAD, four on chronic NSNP, and one on chronic mixed WAD and NSNP. In acute WAD, meta-analysis indicated no difference in tumour necrosis factor (TNF)-α compared with controls (SMD: 0.45 [95%CI -0.05, 0.95], p = 0.08, I2 = 24%). Meta-analysis revealed that chronic neck pain (mixed WAD and NSNP) was associated with raised TNF-α (SMD: 0.59 [95% CI 0.09, 1.09], p = 0.02, I2 = 45%) and interleukin-1β (SMD: 0.84 [95% CI 0.24, 1.44], p = 0.01, I2 = 59%), but there were no group differences for monocyte chemoattractant protein-1 (SMD: 0.10 [95% CI -0.78, 0.98], p = 0.82, I2 = 77%). Meta-analysis quality of evidence was typically low due to high heterogeneity and small sample sizes. Best evidence synthesis indicated limited evidence of increased C-reactive protein (CRP) in acute WAD, whereas there was moderate evidence of an association between chronic neck pain and raised CRP. In individual studies in acute and chronic WAD, raised CRP was associated with hyperalgesia to pressure and thermal stimuli, and TNF-α was positively correlated with pain catastrophising. In chronic NSNP, increased CRP and macrophage inflammatory protein-1β were associated with higher pain intensity.
Conclusion(s): Results suggest that raised blood inflammatory markers are associated with neck pain and this may reflect a systemic inflammatory process. In acute WAD, this could represent an immune response to trauma. In long-term neck pain, prolonged low-grade inflammation may be secondary to an unresolved tissue injury (chronic WAD) or ongoing tissue stress (chronic NSNP).
Implications: Systemic inflammation could plausibly account for some clinical features associated with neck pain. For example, immune-mediated sensitisation of peripheral nociceptors may contribute to widespread hyperalgesia in WAD. Future research should explore possible clinical applications of inflammatory blood markers in management of neck pain, such as utility as a prognostic marker or assisting with treatment selection.
Funding, acknowledgements: Nil specific funding received for this study
Keywords: Neck pain, Whiplash Injuries, Inflammation
Topic: Musculoskeletal: spine
Did this work require ethics approval? No
Institution: N/A
Committee: N/A
Reason: Systematic Review
All authors, affiliations and abstracts have been published as submitted.
