Placebo in Orofacial Pain: a Systematic Review of Experimental Studies

Objectives: In clinical treatment studies, nonactive agents or treatments are used to distinguish the specific treatment effect (e.g. pharmacological activity) from non-specific (placebo) effects. In experimental studies, the placebo effect is conceivably also present and may confound the results. This systematic review aimed to evaluate and summarize the placebo effect in experimental orofacial pain trials.
Methods: The review was registered in Prospero (CRD42021223649) and conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A literature search in MEDLINE via PubMed, Scopus and Cochrane from inception until November 2020 was combined with a hand search to identify eligible studies. Risk-of-bias analysis according to Cochrane RoB 2.0 is ongoing by two independent reviewers and will be followed by an updated search to retrieve the most recent publications.
Results: The electronic search identified 2575 publications, of which 1477 remained after removal of duplicates. Irrelevant publications were removed after screening of abstracts (n=909), and clinical treatment studies were also excluded (n=510). Full text assessment of the 58 remaining publications resulted in 35 included placebo-controlled experimental studies. Of these 35 trials, 28 reported no effect related to placebo in the experiments, and 7 trials reported minimal pain reduction using placebo.
Conclusions: The majority of the included experimental trials reported no clear placebo effect in the treatment of experimental orofacial pain. With few exceptions, active agents had a greater treatment effect than placebo. To verify the validity of this conclusion, a quality assessment of the included studies is necessary.