The effects of mobilization and manipulation on mortality and structure, function and inflammatory markers in cervical blood vessels: a systematic review and meta-analysis of studies in healthy animals and animals with pre-existing vascular pathology

Background The safety of cervical spinal manipulative therapy (cSMT) remains debated. Although generally considered safe, cSMT has been linked to rare vascular complications such as cervical arterial dissection and cerebrovascular events. One hypothesis is that pre-existing vascular conditions may increase susceptibility to mechanical forces induced by cSMT, but supporting evidence is limited. Considering ethical and practical constraints in human research, these potential adverse events can only be studied in animal models. Aim To evaluate the effects of cSMT on structure, function and inflammatory markers of cervical arteries and mortality in healthy animals and animals with vascular pathology. Methods A systematic search of PubMed, Embase.com and EBSCO/CINAHL was conducted on March 19, 2025 to identify controlled experimental studies on the effects of cSMT in animals with and without vascular pathology. Two independent reviewers conducted study selection, risk of bias assessment and data extraction. Random-effects meta-analyses were performed for stenosis rate, cross-sectional area, mechanical properties (load, stress, strain), blood flow parameters (velocity, volume), and inflammatory markers (high sensitivity C-Reactive Protein and macrophages). Hedges g was used to report effect sizes. Results Six studies met the selection criteria. Most showed unclear risk of bias. In healthy animals, cSMT had no significant effect on stress, strain or blood flow volume ( n = 2). In animals with vascular pathology, cSMT significantly increased macrophage infiltration ( n = 2), but had no effect on stenosis rate ( n = 3), cross-sectional area ( n = 2), stress ( n = 2), strain ( n = 2) or peak systolic velocity ( n = 2). In animals with vascular pathology compared to healthy animals receiving cSMT, mechanical strain decreased significantly ( n = 2), while no difference was found for mechanical stress ( n = 2). No study reported mortality as an outcome. Conclusion In animals with vascular pathology, cSMT increases inflammatory responses and atherosclerosis reduces tensile strain of cervical arteries. These findings warrant cautious interpretation and may not translate to humans. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD42023471983 , PROSPERO CRD42023471983.