Recovery of inferior alveolar nerve by photobiomodulation therapy using two laser wavelengths: A behavioral and immunological study in rat.

Postoperative sensory disturbances of inferior alveolar nerve (IAN) are major challenges in dental procedures. We aimed to investigate the effect of photobiomodulation therapy (PBMT) with 810 nm and 980 nm diode lasers on behavioral and immunological factors in a rat IAN crush model. Seventy-two rats were randomly assigned to the four groups of 810 nm laser (crush injury+810 nm laser; 6 J/cm2, 15 sessions, every 48 h), 980 nm laser (crush injury+980 nm laser; same protocol), control (crush injury without irradiation), and sham surgery (no crush injury and no irradiation). The neurosensory response of IAN was evaluated by Von Frey behavioral test before (baseline) and post-surgery in a period of one month. Changes of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), nuclear factor-kappa B (NF-κB), TNF-α, and IL-1ß, were assessed on days 2 and 30 post injury. Data were analyzed for significant differences by repeated measures and one-way ANOVA (p < .05). One day after surgery, all rats subjected to nerve injury showed significant increase in the withdrawal threshold of von Frey test compared to the baseline (p = .02 for control and p = .03 for laser groups). The threshold gradually returned to the baseline scores in 810 nm, 980 nm, and control groups from days 11, 17, and 29, respectively. There was a significant lower withdrawal threshold in 810 nm and 980 nm laser groups compared to the control group in days 11 to 19 and 9 to 23, respectively. At both time points, the levels of NGF and BDNF were significantly higher in 810 nm laser group compared to the control group. There was a significant difference between laser and control groups regarding NF-κB expression (all p values<.001). TNF-α and IL-1ß were significantly lower in laser groups compared to the control group (all p values < .001). PBMT with 810 and 980 nm diode laser protocol used in this study, promoted the neurosensory recovery of IAN after crush injury in rats. In addition, application of 810 nm diode laser was associated with more improvement in immunological responses compared to that of 980 nm laser.

Inferior alveolar nerve transection disturbs innate immune responses and bone healing after tooth extraction.

Coordination between the nervous and innate immune systems to maintain bone homeostasis is largely uncharacterized. The present study investigated the sensory-immune interaction in resting alveolar bone and healing socket by surgical sensory denervation. Bone histomorphometry and immunohistochemistry showed that sensory denervation resulted in moderate suppression of bone remodeling, with a proinflammatory milieu manifested by increased neutrophil recruitment and possible alternations in macrophage phenotypes along the resting bone surface. This denervation effect intensified when bone remodeling was triggered by tooth extraction, as revealed by disrupted temporospatial variations in macrophage subpopulations and neutrophil infiltration, which were closely associated with a dramatic decline in socket bone filling and residual ridge height. Antagonism of calcitonin gene-related peptide (CGRP) brought about similar antianabolic and proinflammatory effects as sensory denervation, suggesting that sensory nerves may monitor the bony milieu by CGRP. Depletion of macrophages, rather than neutrophils, ruled out CGRP effects, illustrating that macrophages were the primary immune mechanism that linked sensory innervation, innate immunity, and bone. The data support that sensory innervation is required for control of innate immune responses and maintenance of bone homeostasis. Sensory neuropeptides, such as CGRP, are a possible target for the development of proanabolic treatments in bone disease by modulating innate immune responses.

Effect of inferior alveolar nerve axotomy on immune cells and nerve fibres in young rat molars.

Denervation has been a useful approach to the investigation of interactions between nerve fibres and the pulp-dentine complex. Information on the immunological implications of axotomy is still lacking. The effect of axotomy on CD43+, CD4+, CD11b+ and I-A antigen-expressing cells in both the distal segment of the cut inferior alveolar nerve and in the first molar pulp of young rats was evaluated. Nerve fibres immunoreactive to protein gene product (PGP) 9.5, the neuropeptides substance P and calcitonin gene-related peptide (CGRP), and neuropeptide Y were visualized also by use of the avidin-biotin peroxidase complex method. Recruitment of macrophages was found in the distal segment of the sectioned inferior alveolar nerve 2 days after axotomy, with a further increase in number during the 6-day observation period. However, in the dental pulp, the number of CD43+, CD4+, CD11b+ and I-A antigen-expressing cells was almost unaffected. An almost complete sensory denervation of the first mandibular molar pulp was obtained 2 days after axotomy. After 6 days, the mesial part of the coronal pulp still remained denervated, while regenerated nerve fibres had reached both the root pulp and the distal part of the coronal pulp. Nerve fibres immunoreactive to neuropeptide Y were slightly reduced in density 2 days after axotomy, and after 6 days the localization of neuropeptide Y-immunoreactive fibres was changed compared to the control, with fibres also distributed in the odontoblast layer close to dentine. Hence, following axotomy in young rats, an almost complete sensory denervation is achieved in the first molar, whereas nerve fibres immunoreactive to neuropeptide Y change their distribution pattern, with fibres located close to the dentine after 6 days. Due to the almost unchanged number and distribution of immunocompetent cells in the pulp after axotomy, the young rat molar pulp may represent a suitable and useful experimental model to study neuro-immune interactions.

[The effect of the transsection of the inferior alveolar nerve on neurogenic inflammation of the mouth mucosa. II. Immunohistochemical studies]. / A nervus alveolaris inferior átmetszésének hatása a szájnyálkahártya neurogén gyulladása. II. Immunhisztokémiai vizsgálatok.

The distribution of nerve fibers displaying calcitonin gene-related peptide (CGRP) immunoreactivity in the mandibular mucosa was studied in control rats, in rats after unilateral transection of the inferior alveolar nerve (IAN), and in animals following cervical sympathetic denervation. According to the results, the transection of the peripheral branch of the IAN has no effect on the distribution of the CGRP immunoreactive nerves.