Background: The clinical therapeutic benefits of Photobiomodulation (PBM) therapy have been well established in many clinical scenarios. However, we are far from having developed a complete understanding of the underlying mechanisms of photon-biological tissue interactions. Concurrent to ongoing PBM studies, there are several parallel fields with evidences from cell and tissue physiology such as evolutionary biology, photobiology, and microbiology among others. Objective: This review is focused on extrapolating evidences from an expanded range of studies that may contribute to a better understanding of PBM mechanisms especially focusing on analgesia. Further, the choice of a PBM device source and relevant dosimetry with regards to specific mechanisms are discussed to enable broader clinical use of PBM therapies. Materials and methods: This discussion article is referenced from an expanded range of peer reviewed publications, including literature associated with evolutionary biology, microbiology, oncology, and photo-optical imaging technology, amongst others. Results and discussion: Materials drawn from many disparate disciplines is described. By inference from the current evidence base, a novel theory is offered to partially explain the cellular basis of PBM-induced analgesia. It is proposed that this may involve the activity of a class of transmembrane proteins known as uncoupling proteins. Furthermore, it is proposed that this may activate the heat stress protein response and that intracellur microthermal inclines may be of significance in PBM analgesia. It is suggested that the PBM dose response as a simple binary model of PBM effects as represented by the Arndt-Schulz law is clinically less useful than a multiphasic biological response. Finally, comments are made concerning the nature of photon to tissue interaction that can have significance in regard to the effective choice and delivery of dose to clinical target. Conclusions: It is suggested that a re-evaluation of phototransduction pathways may lead to an improvement in outcome in phototheraphy. An enhanced knowledge of safe parameters and a better knowledge of the mechanics of action at target level will permit more reliable and predictable clinical gain and assist the acceptance of PBM therapy within the wider medical community.
Keywords: analgesia; electron transport chain; mitochondria; photobiomodulation; uncoupled protein responses.