In the realm of medical innovation, the application of photobiomodulation has emerged as a promising approach for treating nerve injuries in the oral district [17,18,19]. The quest to optimize this therapy hinges upon selecting the appropriate laser type and wavelengths. Researchers delve into the intricate interplay between laser characteristics and their compatibility with the unique anatomical and physiological aspects of the oral nerve network. An exploration of the optimal laser type, such as low-level laser therapy (PBMT), and the most effective wavelengths unfolds as a pivotal pursuit [18,19]. As the medical community strives to unravel the potential of photobiomodulation, questions abound regarding the outcomes that it yields in terms of the recovery of nervous function. Preliminary findings hint at the tantalizing prospect of accelerated nerve regeneration, potentially offering a new ray of hope for patients grappling with nerve injuries in the oral district [20,21,22]. By examining the documented results, insights emerge into the extent of neural recovery, improvements in sensory and motor functions, and the overall quality of life enhancements experienced by individuals subjected to this innovative treatment paradigm. As research continues to illuminate the intricate mechanisms underlying photobiomodulation, a clearer picture emerges of its transformative potential in revitalizing nerve function and ushering in a new era of oral nerve injury rehabilitation [20,21,22].

The potential of laser light to impact the peripheral nervous system has been explored in both the neuromuscular and somatosensory systems. This investigation dates to 1978 when it was discovered that laser radiation directed at exposed nerve tissue had a direct and beneficial effect as a preventive measure and a therapeutic intervention [23]. Currently, the preferred treatment for peripheral nerve injuries is advanced microsurgical repair or autologous nerve grafting. However, functional recovery is often unsatisfactory, and there is a need for new therapeutic approaches. Schwann cells in the peripheral nervous system play a crucial role in nerve repair. Various strategies, like pharmacological and cell-based therapies, have been used to enhance recovery, but none provide a universal cure and may have drawbacks and side effects [24]

Various treatment methods, including exercise, electrical stimulation (ES), magnetic stimulation, low-intensity ultrasound (LIU), and phototherapy, have been explored to enhance peripheral nerve regeneration. Exercise, especially aerobic activities like swimming and walking, promotes axonal growth and synaptic improvement, and when combined with ES, it shows better outcomes. Magnetic stimulation increases axon numbers and diameters, likely through stimulating NGF activity. A low-intensity ultrasound induces positive responses by promoting blood circulation and releasing neurotrophic factors. Phototherapy and photobiomodulation therapy (PBMT) also aid in axonal regeneration and functional recovery. PBMT, utilizing low-level infrared light, stimulates SC proliferation and axonal diameter expansion, yet standardized application parameters remain a challenge [25].

Subsequently, in 1992, Rochkind and Ouaknine [26] demonstrated that photobiomodulation therapy (PBMT) influenced the electrical activity and morphology of injured and intact peripheral nerves in rats. They observed that the action potential of intact nerves increased by up to 33% following a single transcutaneous laser treatment. Similarly, injured nerves subjected to corresponding therapy exhibited a significantly increased action potential amplitude compared to untreated injured nerves [26].

Hakimiha and colleagues [27] conducted an investigation using a rat model to assess the effectiveness of PBMT on nerve regeneration. Their findings revealed that in studies involving highly metabolically active cells like nerve tissue, unfavorable outcomes were more commonly attributed to excessive dosing rather than insufficient dosing. In the current research, a notably expedited nerve recovery was achieved using an energy density of 6 J/cm². This discovery lends support to the notion of a “biphase dose-response” phenomenon in PBMT, wherein positive biostimulation responses are triggered at doses below 10 J/cm², while inhibitory responses are prominent at doses surpassing 20 J/cm² [27]. Nevertheless, this concept of a “window effect” has been extensively examined in existing literature, and the findings from the study under consideration align well with the established data in this field.

The results obtained from the immunoblotting analysis conducted on the second day after the injury indicated elevated concentrations of the nerve growth factor (NGF) in rats that underwent PBMT treatment, in comparison to the control group that did not receive PBMT. This rise in NGF levels corresponded with a swifter restoration of neurosensory functionality [26]. Likewise, a multitude of other investigations, encompassing both controlled and uncontrolled trials, have highlighted favorable subjective enhancements attributed to PBMT across diverse clinical contexts, such as perioral lesions [26], recovery after musculoskeletal surgery [24], and the promotion of osteogenic differentiation [27]. To sum up, PBMT manifests positive influences on distinct nervous, musculoskeletal, and epithelial systems.

In the research carried out by Sharifi et al., the impact of photobiomodulation on the recuperation of the sensory function in the lip and chin following bilateral sagittal split osteotomy (BSSO) was examined [26]. The procedure involved the utilization of a GaAs diode laser emitting continuous waves at a wavelength of 980 nm, generating a power output of 100 mW, and delivering an energy density of 12 J/cm². Substantial enhancements were noted in the scores recorded on the visual analogue scales (VAS) for general sensitivity, discrimination of pain, recognition of direction, and discrimination of two points, both after a span of 30 days and once more after 60 days [26].

Gasperini et al. [28], Bashiri et al. [29], Salari et al. [30], Pinto et al. [32], Fuhrer-Valdivia et al. [33], and Ozen et al. [34] used the GaAlAs laser in their trials with wavelengths between 789 and 880 nm; according to their studies, their photobiomodulation protocol could significantly improve healing and sensibility could be regained after nerve injury, based on an improvement on pain scales and mechanical test results. Salari et al. [30], however, show that there is no statistical difference between the control group and the treatment group in regards to thermal sensitivity in all the periods examined, while all three authors agree that during the follow-up, the mechanical tests have better results [28,29,30,32,33,34,35,36,37].

The diode laser was used respectively by Miloro et al. [27], Qi et al. [31], Eshghpour et al. [38], De Oliveira et al. [39], Teixera-Santos et al. [36], and Mohajerani et al. [35].

Except for the trial conducted by Miloro et al., the diode laser could be considered as effective as the GaAlAs laser; in fact, in all of the studies, there is a significance in the improvement of pain relief, quality of life, and faster healing. Diode laser wavelengths were used between 632 and 880 nm, in a continuous mode and with the scanning method [27,31,35,36,38,39].

As far as photobiomodulation is concerned, the authors mostly used diode lasers or GaAs or GaAlAs lasers, and only in one case, a LED laser is used. The wavelengths used vary from a range from 632 to 910 nm for an application time of at least 10 sessions. Most of the treatments were administrated with a continuous wave. All of the authors report, because of the experimentation, an objective and subjective improvement of the symptoms without side effects, although in some cases, it was a matter of very long therapeutic plans in terms of time. In the cited studies, none of the authors report medium and long-term follow-ups of the effects of photobiomodulation on the patients examined. 

Photobiomodulation is a non-invasive therapeutic approach, as the literature confirms, that involves the use of light to stimulate cellular activity and promote tissue regeneration. It has shown promising results in the regeneration of peripheral nerves. Studies conducted on animal models, such as rats [41,42,43,44,45,46,47,48,49,50,51,52], have demonstrated that PBM can enhance nerve regeneration by promoting axonal growth, reducing inflammation, and increasing cellular metabolism. These experiments typically involve applying specific wavelengths of light to the injured nerve area, leading to improved nerve function and accelerated healing [53,54,55,56]. While more research is needed to fully understand the underlying mechanisms and optimize treatment protocols, the potential of photobiomodulation as a tool for peripheral nerve regeneration is an exciting avenue for future medical applications [57,58,59]. Indeed, for a targeted photobiomodulation treatment aimed at recovering sensitivity following peripheral nerve injury, specific wavelengths of light are typically used [57,58,59,60,61,62,63,64]. Wavelengths within the near-infrared range (600–1100 nm) are commonly employed for this purpose. These wavelengths have a greater ability to penetrate tissues and reach the nerve fibers, allowing for deeper stimulation and interaction with cellular components. Wavelengths around 800–850 nm are often favored due to their optimal tissue penetration and interaction with the mitochondrial enzyme cytochrome c oxidase [57,58,59,60,61,62,63,64]. This interaction triggers a cascade of cellular responses, including enhanced ATP production, reduced oxidative stress, and the modulation of signaling pathways involved in nerve repair and regeneration. Furthermore, wavelengths in the red-light range (around 630–670 nm) can also contribute to the stimulation of cellular activity and blood flow, aiding in tissue oxygenation and nutrient supply to support nerve healing. By utilizing these specific wavelengths, photobiomodulation can effectively promote nerve tissue repair, axonal growth, and sensory function recovery after peripheral nerve injury. However, it is important to note that treatment parameters, such as power density, duration, and frequency of exposure, need to be carefully optimized based on the severity of the injury and individual patient characteristics for optimal therapeutic outcomes [64,65,66,67,68,69,70,71].

A wide array of therapeutic approaches are employed to mitigate pain, showcasing the versatility of medical interventions in addressing this complex issue. These methods encompass the utilization of painkillers, which encompass both non-opioid analgesics and anti-inflammatory medications, offering rapid relief by targeting pain pathways and reducing inflammation [72,73,74,75,76,77]. Additionally, corticosteroids find application due to their potent anti-inflammatory properties, effectively alleviating pain associated with inflammatory conditions. Painkillers play a pivotal role in managing neuropathic pain, a complex condition characterized by aberrant nerve signaling. Drugs such as tricyclic antidepressants, anticonvulsants, and serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly prescribed. These medications target specific pathways involved in nerve transmission and modulation, helping to alleviate the distinctive burning, shooting, or tingling sensations associated with neuropathic pain [72,73,74,75,76,77]. While painkillers offer relief, their effectiveness varies among individuals, and a multidisciplinary approach may be needed for comprehensive neuropathic pain management. In cases where nerve-related pain is a concern, nerve denervation, or ablation, emerges as a potential solution. By interrupting the transmission of pain signals along the affected nerves, this technique can provide substantial relief. Similarly, muscle relaxants are employed to ease pain stemming from muscle tension or spasms, allowing for enhanced comfort and improved mobility. Nerve denervation or ablation is considered in cases of severe neuropathic pain that is unresponsive to conservative treatments [72,73,74,75,76,77]. This procedure involves deliberately disrupting the nerve pathways responsible for transmitting pain signals, often providing relief when other methods have failed. The decision to opt for nerve denervation is based on several criteria. Firstly, a thorough evaluation of the patient’s medical history, pain duration, and response to prior treatments is conducted [76]. Candidates for denervation typically exhibit localized neuropathic pain that is well-defined and refractory to conventional interventions. Moreover, imaging studies, such as MRI or nerve blocks, may be utilized to precisely identify the pain source and the nerves involved. A successful nerve denervation outcome hinges on accurate identification and targeting of the specific nerve responsible for the pain. Patient selection is critical, with consideration given to factors such as overall health status, potential risks of the procedure, and the patient’s willingness to undergo a more invasive treatment approach [72,73,74]. The outcomes of nerve denervation can vary, with some patients experiencing significant and sustained pain relief, while others may see only partial improvement. The procedure’s success often depends on the nerve’s regrowth capacity and the underlying cause of neuropathy. Post-denervation rehabilitation, including physical therapy, is crucial to optimize outcomes. The close collaboration between the patient, pain specialist, and interdisciplinary team is vital to making informed decisions regarding nerve denervation as a therapeutic option for refractory neuropathic pain [72,73,74,75,76,77]. Physical therapy is a cornerstone in pain management, focusing on rehabilitation, strengthening, and restoring functional capacity. This approach not only addresses the root causes of pain but also empowers patients with long-term coping mechanisms and an improved overall well-being. An intriguing avenue lies in the administration of parietal hyaluronic acid preparations or biological substances, such as stem cells [72,73,74,75,76,77]. These innovative therapies target tissue regeneration and repair, holding the potential for more sustainable pain relief by addressing underlying structural issues. Stem cells hold considerable promise as a potential therapeutic avenue for neuropathic pain management. These versatile cells have the capacity to differentiate into various cell types and secrete bioactive molecules that can modulate inflammation, tissue repair, and nerve regeneration. In the context of neuropathic pain, stem cell therapy aims to address underlying pathophysiological mechanisms by promoting nerve tissue regeneration and reducing neuroinflammation [72,73,74,75,76,77]. Preclinical studies involving animal models have demonstrated encouraging results, showing improved pain-related behaviors and enhanced nerve function after stem cell transplantation. However, translating these findings into clinical practice requires careful consideration of factors such as the stem cell source, delivery methods, and long-term safety and efficacy. While stem cell-based therapies offer a promising avenue for neuropathic pain treatment, further research and clinical trials are necessary to establish their definitive role and optimize their potential benefits. It is noteworthy, however, that while each of these interventions demonstrates efficacy to varying extents, their impact tends to be temporally constrained, usually offering relief for a limited duration, spanning from several weeks to a few months [72,73,74,75,76,77]. To further the discourse, I propose an expansion of the discussion section, guided by the following essential questions, thereby delving deeper into the long-term effectiveness, potential synergies, and avenues for enhancing the durability of pain management interventions [72,73,74,75,76,77].