Open Access
Open access
volume 20 issue 3 pages e0319586

The mechanisms of manual therapy: A living review of systematic, narrative, and scoping reviews

Damian L. Keter 1
Joel E. Bialosky 2
Kevin Brochetti 1
Carol A. Courtney 3
Martha Funabashi 4
Steve Karas 5
Kenneth Learman 6
Chad Cook 7
Publication typeJournal Article
Publication date2025-03-18
scimago Q1
wos Q2
SJR0.803
CiteScore5.4
Impact factor2.6
ISSN19326203
Abstract
Introduction

Treatment mechanisms are the underlying process or pathway through which a treatment influences the body. This includes molecular, cellular and physiological processes or pathways contributing to treatment effect. Manual therapy (MT) evokes complex mechanistic responses across body systems, interacting with the individual patient and context to promote a treatment response. Challenges arise as mechanistic studies are spread across multiple professions, settings and populations. The purpose of this review is to summarize treatment mechanisms that have been reported to occur with MT application.

Methods

Four electronic databases were searched (Medline, CINAHL, Cochrane Library, and PEDro) for reviews investigating mechanistic responses which occur during/post application of MT. This review was registered a priori with PROSPERO (CRD42023444839). Methodological quality (AMSTAR-2) and risk of bias (ROBIS) were assessed for systematic and scoping reviews. Data were synthesized by mechanistic domain.

Results

Sixty-two reviews were included. Systematic reviews (n = 35), narrative reviews (n = 24), and scoping reviews (n = 4) of asymptomatic (n = 37), symptomatic (n = 43), non-specified human subjects (n = 7) and animals (n = 7) were included. Reviews of moderate quality supported neurovascular, neurological, and neurotransmitter/neuropeptide changes. Reviews of low quality supported neuroimmunce, neuromuscular, and neuroendocrine changes. Reviews of critically low quality support biomechanical changes.

Conclusions

Findings support critically low to moderate quality evidence of complex multisystem mechanistic responses occurring with the application of MT. Results support peripheral, segmental spinal, and supraspinal mechanisms occurring with the application of MT, which can be measured directly or indirectly. The clinical value of these findings has not been well established. While MT has proven to be an effective intervention to treat conditions such as pain, the current body of literature leaves uncertainty as to ‘why’ MT interventions work, and future research should look to better define which mechanisms (or combinations of mechanisms) are mediators of clinical response.

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Keter D. L. et al. The mechanisms of manual therapy: A living review of systematic, narrative, and scoping reviews // PLoS ONE. 2025. Vol. 20. No. 3. p. e0319586.
GOST all authors (up to 50) Copy
Keter D. L., Bialosky J. E., Brochetti K., Courtney C. A., Funabashi M., Karas S., Learman K., Cook C. The mechanisms of manual therapy: A living review of systematic, narrative, and scoping reviews // PLoS ONE. 2025. Vol. 20. No. 3. p. e0319586.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1371/journal.pone.0319586
UR - https://dx.plos.org/10.1371/journal.pone.0319586
TI - The mechanisms of manual therapy: A living review of systematic, narrative, and scoping reviews
T2 - PLoS ONE
AU - Keter, Damian L.
AU - Bialosky, Joel E.
AU - Brochetti, Kevin
AU - Courtney, Carol A.
AU - Funabashi, Martha
AU - Karas, Steve
AU - Learman, Kenneth
AU - Cook, Chad
PY - 2025
DA - 2025/03/18
PB - Public Library of Science (PLoS)
SP - e0319586
IS - 3
VL - 20
SN - 1932-6203
ER -
BibTex |
Cite this
BibTex (up to 50 authors) Copy
@article{2025_Keter,
author = {Damian L. Keter and Joel E. Bialosky and Kevin Brochetti and Carol A. Courtney and Martha Funabashi and Steve Karas and Kenneth Learman and Chad Cook},
title = {The mechanisms of manual therapy: A living review of systematic, narrative, and scoping reviews},
journal = {PLoS ONE},
year = {2025},
volume = {20},
publisher = {Public Library of Science (PLoS)},
month = {mar},
url = {https://dx.plos.org/10.1371/journal.pone.0319586},
number = {3},
pages = {e0319586},
doi = {10.1371/journal.pone.0319586}
}
MLA
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MLA Copy
Keter, Damian L., et al. “The mechanisms of manual therapy: A living review of systematic, narrative, and scoping reviews.” PLoS ONE, vol. 20, no. 3, Mar. 2025, p. e0319586. https://dx.plos.org/10.1371/journal.pone.0319586.