Advanced, pharmacological and complementary interventions for chronic or recurrent orofacial pain conditions: a systematic evidence map with selective meta-analyses
J Headache Pain. 2026 Feb 28. doi: 10.1186/s10194-026-02300-7. Online ahead of print.
ABSTRACT
BACKGROUND: Advanced technologies and complementary or adjunctive interventions are increasingly used for chronic or recurrent orofacial pain (OP), but comparative evidence remains fragmented across diagnoses, modalities, and outcomes.
MAIN BODY: We conducted a systematic evidence map with selective meta-analyses (PROSPERO CRD420251270501) following PRISMA 2020. Six databases were searched from inception to 31 December 2025 for randomized and non-randomized intervention studies in adults with temporomandibular disorders (TMD), burning mouth syndrome (BMS), trigeminal neuralgia (TN), and other chronic or recurrent orofacial pain phenotypes. Two reviewers independently screened records, extracted data, assessed risk of bias using validated tools, and rated certainty with GRADE. Random-effects meta-analyses of randomized comparisons used standardized mean differences within prespecified follow-up windows and reported prediction intervals. Pain intensity was prioritized, and disability, jaw function, quality of life, global improvement, medication outcomes, and adverse events were extracted when available. We included 130 studies (n = 6879 participants). Non-randomized intervention studies were retained to widen the evidence map and to capture feasibility, durability, and safety signals that are often underrepresented in early randomized trials. These studies were synthesized narratively and did not contribute to pooled comparative estimates or to certainty upgrading. Low risk of bias was uncommon, and reporting of function, quality of life, and harms was inconsistent, which limited pooling. Safety outcomes were not reported in 37 of 130 included studies, and denominators were often unclear, which limits risk-benefit interpretation. In BMS, photobiomodulation or low-level laser therapy (PBM/LLLT) versus inactive control reduced short-term pain (k = 6, N = 200, standardized mean difference - 0.81, 95% CI - 1.35 to - 0.27). The 95% prediction interval crossed the null (- 1.80 to 0.17), while certainty was moderate. Most pharmacologic and supplement interventions for BMS showed uncertain or inconsistent effects. For TMD, effects varied by modality and comparator and were generally low or very low certainty. Evidence for TN and digital therapeutics was sparse, and adverse-event reporting was inconsistent.
SHORT CONCLUSION: PBM/LLLT shows the clearest short-term analgesic signal for BMS versus inactive control, but transportability remains uncertain given null-crossing prediction intervals and limited long-term data. Future trials should standardize outcomes, extend follow-up, and report harms transparently to support diagnosis-stratified care.
PMID:41761060 | DOI:10.1186/s10194-026-02300-7