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

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.

Comparison of Ozone and Photo-Biomodulation Therapies on Mental Nerve Injury in Rats.

PURPOSE: This study compared photo-biomodulation (PBM) and ozone therapy (OT) for mental nerve injury by counting Schwann cells (SCs) and fasciculated nerve branches and measuring fascicular nerve areas. MATERIALS AND METHODS: The effects of OT and PBM on mental nerve injury were evaluated. Mental nerves of 27 rats were partly sutured and allocated into 3 groups. Group 1 received no treatment, group 2 received OT, and group 3 received PBM. The number of fascicules beyond nerve branches and the number of SCs before and after nerve injury were evaluated histologically. RESULTS: A better healing pattern was observed in the treatment groups. The number of SCs was markedly larger in the OT and PBM groups than in the control group. CONCLUSIONS: Oral and maxillofacial surgeons should be familiar with the differential diagnosis, prevention, and management of neurosensory disturbances. This study provides insights into the management of neurosensory disturbances related to mental nerve injury using OT and PBM. This study clearly suggests that OT and PBM are promising novel methods for the treatment of mental nerve injury.

Effect of Low-Level Laser and Light-Emitting Diode on Inferior Alveolar Nerve Recovery After Sagittal Split Osteotomy of the Mandible: A Randomized Clinical Trial Study.

PURPOSE: The major concern of sagittal split osteotomy (SSO) is the neurosensory disturbance. The authors investigated the effect of low-level laser therapy and light-emitting diode on the inferior alveolar nerve recovery after SSO. METHODS: In this double-blinded randomized clinical trial, 20 subjects with inferior alveolar nerve injury after SSO of the mandible were studied. Neurosensory recovery was assessed by 6 tests: visual analog scale (VAS), brush stroke, 2-point discrimination, contact detect detection, pinprick nociception, and thermal discrimination, and each one was performed before and after the surgery on days 1, 3, 7, 14, 60, and 180. RESULTS: After 1 week, the VAS score in the laser group significantly improved in comparison with the control group. Visual analog scale score improvement was 25% (P = 0.015) at 2 weeks, 21% (P = 0.001) at 2 months, and 24% (P = 0.001) at 6 months. After 2 weeks, the brush stroke score improvement was significant in the laser group. The improvement values were 21.5% (P = 0.002) at 2 months and 15.1% (P = 0.004) at 6 months. CONCLUSION: Low-level laser therapy and light-emitting diode may improve VAS scores, 2-point discrimination, and brush stroke test results without any effect on the pinprick or contact detection test results.

Effect of Low-intensity Pulsed Ultrasound on the Mandibular Remodeling Following Inferior Alveolar Nerve Transection.

Objective To investigate the effects of low-intensity pulsed ultrasound (LIPUS) on the mandibular remodeling following inferior alveolar nerve transection (IANX) and to optimize the parameters of LIPUS in the treatment of nerve injury. Methods IANX was performed in male Sprague-Dawley rats. Four weeks after IANX,the effect of daily LIPUS (from day 1) on the transected inferior alveolar nerve was examined in terms of sensitivity to mechanical stimulation. Moreover,histopathologic changes of mandibles were analyzed by micro-CT,HE staining,Masson trichrome staining,and immunohistochemical staining. Results LIPUS promoted the recovery of inferior alveolar nerve injury after transection. HE staining displayed the improvement of trabecular thickness and continuity. LIPUS with higher duty ratios had more obvious effect on bone remodeling. Conclusion LIPUS promotes the mandibular remodeling following IANX.

Effect of Laser Photobiomodulation with Gradual or Constant Doses in the Regeneration of Rats' Mental Nerve After Lesion by Compression.

OBJECTIVE: Assess morphologically the efficacy of constant dose (CD) or gradual dose (GD) in photobiomodulation therapy (PBMT) during the regeneration process of rats' mental nerve after compression lesion. MATERIALS AND METHODS: Forty-eight male Wistar rats were used and divided into four groups (n = 12): negative control (NC): lesion by compression; positive control (PC): no lesion; GD: lesion by compression and PBMT with GD; and CD: lesion by compression and PBMT with CD. One day after the surgery, the groups GD and CD underwent PBMT daily in three equidistant points around the incision area. The parameters were wavelength of 808 nm, 100 mW, CD received treatment with 120 J/cm2, while GD underwent the protocol of application: 1st and 4th sessions: 80 J/cm2; 5th to 8th sessions: 90 J/cm2; 9th to 12th sessions: 100 J/cm2; 13th to 16th sessions: 110 J/cm2; and 17th to 20th sessions: 120 J/cm2. Euthanasias were performed at 3, 7, 14, and 21 days. Qualitative and quantitative analysis of the mental nerves were performed with ANOVA (analysis of variance) and Tukey tests (p ≤ 0.05). RESULTS: It was observed that PBMT was able to accelerate the process of nerve regeneration presenting an increase in the number of myelinated fibers starting at 14 days of treatment for groups CD and GD, and at 21 days they were similar to PC. It was observed a better lamellar organization of myelin sheath at 7 days for GD and at 14 days for CD, similar to PC. Both GD and CD presented significant differences compared to NC and PC for thickness of the myelin sheath, outer perimeter, internal area, and number of myelin fibers. CONCLUSIONS: PBMT presented positive effect on the regeneration of nerve starting at 14 days, and after 21 days there was no difference between GD and CD.

Effects of Superpulsed, Low-Level Laser Therapy on Neurosensory Recovery of the Inferior Alveolar Nerve.

OBJECTIVE: The purpose of this investigation was to evaluate the therapeutic efficacy of superpulsed, low-level laser therapy (SLLLT) on neurosensory recovery of the inferior alveolar nerve (IAN) after oral surgical injury. BACKGROUND DATA: A survey of the literature reveals the uncertainty of outcomes for the surgical management of IAN injury and the efficacy of low-level laser therapy in the treatment of IAN injury. METHODS: In this study, the authors report the results for SLLLT in 57 patients affected by paresthesia of the lip, chin, gingival, and buccal regions. Each patient was subjected to 10 laser treatments, once a week, with a GaAs diode laser. Clinical neurosensory tests (soft touch, 2-point discrimination, pin prick, thermal test) and the visual analogue scale were used before every treatment to evaluate the extent of neurosensory recovery. RESULTS: The authors' results demonstrate that 83.3% of the patients had a significant neurosensory recovery, as evident in the objective and subjective tests. CONCLUSION: The results reported in this study indicate that SLLLT has the potential to improve neurosensory recovery in patients with IAN paresthesia.

Trials needed to identify best management of iatrogenic inferior alveolar and lingual nerve injuries.

DATA SOURCES: The Cochrane Oral Health Group's Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase databases were searched with no language or date restrictions. STUDY SELECTION: Three reviewers independently selected studies. Randomised controlled trials (RCTs) involving interventions to treat patients with neurosensory defect of the inferior alveolar or lingual nerve or both as a sequela of iatrogenic injury were considered. DATA EXTRACTION AND SYNTHESIS: Standard Cochrane methodological procedures were followed. RESULTS: Two studies considered at high risk of bias, reporting data from 26 analysed patients were included. Both studies investigated the effectiveness of low-level laser treatment compared to placebo laser therapy on inferior alveolar sensory deficit as a result of iatrogenic injury. Two studies assessed as at high risk of bias, reporting data from 26 analysed participants were included in this review. The age range of participants was from 17 to 55 years. Both trials investigated the effectiveness of low-level laser treatment compared to placebo laser therapy on inferior alveolar sensory deficit as a result of iatrogenic injury.Patient-reported altered sensation was partially reported in one study and fully reported in another. Following treatment with laser therapy, there was some evidence of an improvement in the subjective assessment of neurosensory deficit in the lip and chin areas compared to placebo, though the estimates were imprecise: a difference in mean change in neurosensory deficit of the chin of 8.40 cm (95% confidence interval (CI) 3.67 to 13.13) and a difference in mean change in neurosensory deficit of the lip of 21.79 cm (95% CI 5.29 to 38.29). The overall quality of the evidence for this outcome was very low. No studies reported on the effects of the intervention on the remaining primary outcomes of pain, difficulty eating, speaking or taste. No studies reported on quality of life or adverse events. CONCLUSIONS: There is clearly a need for randomised controlled clinical trials to investigate the effectiveness of surgical, medical and psychological interventions for iatrogenic inferior alveolar and lingual nerve injuries. Primary outcomes of this research should include: patient-focused morbidity measures including altered sensation and pain, pain, quantitative sensory testing and the effects of delayed treatment.

Interventions for iatrogenic inferior alveolar and lingual nerve injury.

BACKGROUND: Iatrogenic injury of the inferior alveolar or lingual nerve or both is a known complication of oral and maxillofacial surgery procedures. Injury to these two branches of the mandibular division of the trigeminal nerve may result in altered sensation associated with the ipsilateral lower lip or tongue or both and may include anaesthesia, paraesthesia, dysaesthesia, hyperalgesia, allodynia, hypoaesthesia and hyperaesthesia. Injury to the lingual nerve may also affect taste perception on the affected side of the tongue. The vast majority (approximately 90%) of these injuries are temporary in nature and resolve within eight weeks. However, if the injury persists beyond six months it is deemed to be permanent. Surgical, medical and psychological techniques have been used as a treatment for such injuries, though at present there is no consensus on the preferred intervention, or the timing of the intervention. OBJECTIVES: To evaluate the effects of different interventions and timings of interventions to treat iatrogenic injury of the inferior alveolar or lingual nerves. SEARCH METHODS: We searched the following electronic databases: the Cochrane Oral Health Group's Trial Register (to 9 October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE via OVID (1946 to 9 October 2013) and EMBASE via OVID (1980 to 9 October 2013). No language restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving interventions to treat patients with neurosensory defect of the inferior alveolar or lingual nerve or both as a sequela of iatrogenic injury. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. We performed data extraction and assessment of the risk of bias independently and in duplicate. We contacted authors to clarify the inclusion criteria of the studies. MAIN RESULTS: Two studies assessed as at high risk of bias, reporting data from 26 analysed participants were included in this review. The age range of participants was from 17 to 55 years. Both trials investigated the effectiveness of low-level laser treatment compared to placebo laser therapy on inferior alveolar sensory deficit as a result of iatrogenic injury.Patient-reported altered sensation was partially reported in one study and fully reported in another. Following treatment with laser therapy, there was some evidence of an improvement in the subjective assessment of neurosensory deficit in the lip and chin areas compared to placebo, though the estimates were imprecise: a difference in mean change in neurosensory deficit of the chin of 8.40 cm (95% confidence interval (CI) 3.67 to 13.13) and a difference in mean change in neurosensory deficit of the lip of 21.79 cm (95% CI 5.29 to 38.29). The overall quality of the evidence for this outcome was very low; the outcome data were fully reported in one small study of 13 patients, with differential drop-out in the control group, and patients suffered only partial loss of sensation. No studies reported on the effects of the intervention on the remaining primary outcomes of pain, difficulty eating or speaking or taste. No studies reported on quality of life or adverse events.The overall quality of the evidence was very low as a result of limitations in the conduct and reporting of the studies, indirectness of the evidence and the imprecision of the results. AUTHORS' CONCLUSIONS: There is clearly a need for randomised controlled clinical trials to investigate the effectiveness of surgical, medical and psychological interventions for iatrogenic inferior alveolar and lingual nerve injuries. Primary outcomes of this research should include: patient-focused morbidity measures including altered sensation and pain, pain, quantitative sensory testing and the effects of delayed treatment.