Mitochondrial Bioenergetic, Photobiomodulation and Trigeminal Branches Nerve Damage, What's the Connection? A Review Author: Silvia Ravera1, Esteban Colombo2, Claudio Pasquale2, Stefano Benedicenti2, Luca Solimei2, Antonio Signore2,3, Andrea Amaroli2,4 Affiliation: <sup>1</sup> Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy. <sup>2</sup> Department of Surgical and Diagnostic Sciences, University of Genoa, 16132 Genoa, Italy. <sup>3</sup> Department of Therapeutic Dentistry, Faculty of Dentistry, First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia. <sup>4</sup> Department of Orthopaedic Dentistry, Faculty of Dentistry, First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia. Conference/Journal: Int J Mol Sci Date published: 2021 Apr 21 Other: Volume ID: 22 , Issue ID: 9 , Pages: 4347 , Special Notes: doi: 10.3390/ijms22094347. , Word Count: 292 Background: Injury of the trigeminal nerve in oral and maxillofacial surgery can occur. Schwann cell mitochondria are regulators in the development, maintenance and regeneration of peripheral nerve axons. Evidence shows that after the nerve injury, mitochondrial bioenergetic dysfunction occurs and is associated with pain, neuropathy and nerve regeneration deficit. A challenge for research is to individuate new therapies able to normalise mitochondrial and energetic metabolism to aid nerve recovery after damage. Photobiomodulation therapy can be an interesting candidate, because it is a technique involving cell manipulation through the photonic energy of a non-ionising light source (visible and NIR light), which produces a nonthermal therapeutic effect on the stressed tissue. Methods: The review was based on the following questions: (1) Can photo-biomodulation by red and NIR light affect mitochondrial bioenergetics? (2) Can photobiomodulation support damage to the trigeminal nerve branches? (preclinical and clinical studies), and, if yes, (3) What is the best photobiomodulatory therapy for the recovery of the trigeminal nerve branches? The papers were searched using the PubMed, Scopus and Cochrane databases. This review followed the ARRIVE-2.0, PRISMA and Cochrane RoB-2 guidelines. Results and conclusions: The reliability of photobiomodulatory event strongly bases on biological and physical-chemical evidence. Its principal player is the mitochondrion, whether its cytochromes are directly involved as a photoacceptor or indirectly through a vibrational and energetic variation of bound water: water as the photoacceptor. The 808-nm and 100 J/cm2 (0.07 W; 2.5 W/cm2; pulsed 50 Hz; 27 J per point; 80 s) on rats and 800-nm and 0.2 W/cm2 (0.2 W; 12 J/cm2; 12 J per point; 60 s, CW) on humans resulted as trustworthy therapies, which could be supported by extensive studies. Keywords: bioenergetic metabolism; inferior alveolar nerve; lingual nerve; low-level laser therapy; mental nerve; nerve injury; nerve regeneration; neuropathic pain; phototherapy; trigeminus. PMID: 33919443 PMCID: PMC8122620 DOI: 10.3390/ijms22094347