A meta-analysis of pain intensity changes after placebo interventions in facial pain

Interpreting pain improvements after interventions in clinical settings is challenging because placebo effects can influence patient-reported outcomes. In clinical practice, pain intensity reductions of 30% or greater are commonly considered indicative of meaningful analgesic benefit. However, the likelihood of achieving such reductions after placebo interventions is not known. We conducted a comprehensive meta-analysis to quantify pain intensity changes reported after placebo interventions in clinical trials of facial pain (FP). We systematically searched for randomized controlled trials (RCTs) and uncontrolled case series of FP treatments that included placebo or sham arms. The primary outcome was percentage change in pain intensity. The primary analysis focused on RCTs, with pooled effect sizes estimated using random-effects meta-analysis. Data from 115 studies (n = 3,208) were analyzed, including 71 RCTs (n = 2,128) and 44 uncontrolled case series (n = 1,080). Sham interventions yielded an average pain reduction of 29.73% (95% CI 24.09%-35.36%), with a prediction interval (-14.51% to 73.96%) among RCTs. Placebo responses varied by diagnosis (P < 0.001), with larger effects in temporomandibular disorders and classical trigeminal neuralgia. Cumulative probability analyses showed that ≥50% pain relief occurred in ∼25% of placebo-treated patients, whereas ≥75% improvement was reported in ∼2.5%. In FP, placebo interventions often produce mild to moderate relief but rarely yield dramatic improvements of ≥75%. These results can guide the interpretation of reported pain relief in clinical settings and inform clinical trial design in chronic pain conditions, suggesting that ≥75% pain intensity reductions after analgesic interventions are unlikely to be primarily driven by placebo effects.