Laser-Based Photobiomodulation for Orthodontic Pain: Mechanistic Evidence from Experimental Tooth-Movement Models

Orthodontic pain, a fundamental biological response to mechanically induced tooth movement, is primarily associated with sterile inflammation and neurogenic processes within the periodontal ligament (PDL). Although photobiomodulation therapy (PBMT) has been widely investigated as a nonpharmacological approach for pain attenuation, its mechanisms of action remain incompletely understood, and current interpretations are often limited to peripheral anti-inflammatory effects. This review re-examines the biological basis of orthodontic pain by integrating evidence derived predominantly from in vitro and in vivo experimental studies. Particular emphasis is placed on neurogenic inflammation, neuropeptide regulation, and neuron-glia interactions along the trigeminal nociceptive pathway. PBMT can reduce periodontal inflammatory/neuropeptide-related markers and pain-related behaviors in selected models; however, evidence for direct central neuron-glia modulation remains largely marker-based and parameter-dependent. Direct functional validation of trigeminal circuit modulation (e.g., electrophysiological recordings or calcium imaging) remains limited in orthodontic pain models; thus, the proposed neuroimmune mechanisms should be interpreted as testable hypotheses for future work. By synthesizing mechanistic insights across multiple biological levels, this review proposes a broader framework for understanding PBMT-mediated pain modulation extending beyond conventional peripheral models. These perspectives may help clarify inconsistencies in the reported outcomes and provide a rationale for future hypothesis-driven experimental and translational research.