Capsaicin for Orofacial Pain Management: Systematic Review and Meta-Analysis

Orofacial pain is a multifactorial condition that severely impacts basic functions and overall quality of life in patients, underscoring the need for non-opioid therapeutic strategies. Targeting the Transient Receptor Potential Vanilloid 1 (TRPV1) pathway has emerged as a biologically plausible approach, given its central role in nociceptive transduction and peripheral sensitization. Capsaicin, a selective TRPV1 agonist, induces receptor desensitization and has shown potential in chronic pain modulation; however, its efficacy in orofacial conditions remains unclear. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of capsaicin in managing orofacial pain, compared to placebo or other pharmacological interventions. Following PRISMA guidelines, a comprehensive search of five databases (PubMed, Scopus, Web of Science, CDSR, and LILACS) was conducted without language or date restrictions. Studies involving human participants with orofacial pain treated with capsaicin were included. The protocol was registered in PROSPERO (CRD420251004538). Risk of bias was assessed using the RoB2, RoB2 crossover trial and ROBINS-I checklist, and meta-analyses were performed using random-effects models. Nine studies enrolling a total of 164 participants met the eligibility criteria and encompassed temporomandibular disorders, burning mouth syndrome, oral mucositis, trigeminal neuralgia, and neuropathic facial pain. Although placebo-controlled comparisons showed a trend toward pain reduction that did not reach statistical significance (MD = -1.87; [95% CI: -3.94, 0.19]; p = 0.08; I² = 86%), and no significant difference was found between capsaicin concentrations (MD = 0.46; [95% CI: -2.67, 3.60]; p = 0.77, I² = 66%), pre-post analyses of uncontrolled (single-arm) studies demonstrated a significant and clinically meaningful reduction in pain following capsaicin treatment (MD = -6.39; [95% CI: -7.40, -5.38; p < 0.001, I² = 0%). Capsaicin also showed an acceptable safety profile: although adverse events were significantly more frequent than with control (OR = 19.84; [95% CI: 4.32-91.21]; p < 0.001, I² = 0%), these were mild, localized, and self-limited. Capsaicin may provide clinically meaningful pain relief in selected orofacial conditions, particularly burning mouth syndrome, where uncontrolled evidence was most consistent (I² = 0%); evidence for temporomandibular disorders was more heterogeneous and did not reach significance in pooled placebo-controlled analyses.