Mitochondrial Bioenergetic, Photobiomodulation and Trigeminal Branches Nerve Damage, What's the Connection? A Review

Abstract

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.

Figure 1

From a cellular point of view, photobiomodulation event is the results of cellular interaction sequences that from the primary target, represented by photoacceptor, move through second messengers and conclude with a modulation of the tissue’s homeostasis. The primary target can be identified in the cytochromes of the mitochondrial respiratory chain (a), the nitrosothiol compounds (b), the lipids (c) and the bounded water (d), which after the interaction with red and, particularly, infrared light, modify their energetic and vibrational state, supporting the release of ATP and ROS (a) and nitric oxide (b), as well as calcium, through the opening of voltage-dependent receptors and release from intra-organellar-sequestered reserves (c,d). Red arrows represent the laser light. Image created with BioRender.com.

Figure 2

Design of the irradiation, site of irradiation and parameters, performed by Diker et al., [36] on a rat affected by an inferior alveolar nerve crush injury. Image created with BioRender.com.

Figure 3

Design of the irradiation, site of irradiation and parameters, performed by Haghighat et al. [47], on patients affected by inferior alveolar nerve and infraorbital nerve damages after bilateral sagittal split osteotomy and Le Fort 1 osteotomy. Image created with BioRender.com.

Figure 4

Organization of the oxidative phosphorylation (OxPhos) machinery. The respiratory chain, located in the inner mitochondrial membrane, consists of five multimeric protein complexes: reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase–ubiquinone oxidoreductase (complex I) contains eight Fe-S clusters involved in the transfer of electrons from reduced flavin mononucleotide (FMNH2) to ubiquinone; succinate dehydrogenase–ubiquinone oxidoreductase (complex II) contains a heme b prosthetic group in its anchor domain, which is essential for the structural integrity and function of the complex; ubiquinone–cytochrome c oxidoreductase (complex III) contains a cytochrome b subunit with two heme moieties, a cytochrome c1 subunit with one heme and a Rieske protein subunit (UQCRFS1) with a [2Fe-2S] cluster, and finally, the cytochrome c oxidase (complex IV), which mediates the final step in the electron transport chain, by catalysing the reduction of oxygen to water. It contains two heme-a moieties and two Cu centres, all of which participate in the electron transfer process to the ATP synthase. Image created with BioRender.com.