The present study has evaluated the therapeutic modalities available for late paresthesia caused by dental procedures or accidents. Currently, studies have mostly focused on preemptive treatments of nerve damage or the treatments adjunctive to dental procedures. Thus, finding a suitable treatment for late paresthesia has been overlooked, and a gold standard treatment has not been agreed upon yet. Moreover, it is worth noting that acute inflammatory mediators, tissue remodeling, and increased hydrostatic pressure of the manipulated tissue may disturb nerve function in the first week following a dental procedure, leading to oral paresthesia. If this condition remains over a week and does not heal spontaneously, it is called late paresthesia.

On the other hand, it was not possible to perform a comprehensive meta-analysis for such a topic, considering the limited number of related studies and their extensive methodologic heterogeneity. For example, the two-point discrimination test was conducted using a caliper [1], two-pronged dry compass [14], or Mackinnon-Dellon Disk-Criminator [16] in the included studies. Moreover, the initial distance between the tips, their sharpness, and even the pressure applied to the skin were not the same in different studies. Such heterogeneity could affect the obtained results.

The treatments proposed for sensation recovery can act through different mechanisms. For example, vitamin B12 (hydroxocobalamin) is one of the treatments recommended for improving nerve damage, considering its role in cellular proliferation and growth, synthesis of nucleoproteins and myelin, repairing peripheral nerves, and improving neural impulse conduction and myelination [25,26,27]. Moreover, one of the evaluated studies in the present systematic review compared the effects of PBM and a combination of vit. B12 and pyrimidine ribonucleotides, including cytidine monophosphate and uridine triphosphate trisodium, which were administered every 8 h for 30 days, on late paresthesia, reporting the beneficial effect of vit B12 on sensation improvement [14]. In a 4-week follow-up, PBM was shown to be significantly more beneficial compared to vitamin B12. However, the group receiving vitamin B12 showed better results compared to the PBM group in a limited number of outcomes such as pain perception. Despite these findings, medical therapy may be preferred by the patients because it is more cost-effective than PBM and eliminates the need for an operator and several visits to a healthcare facility.

As the other group of medications used in the related studies, corticosteroids are commonly prescribed following craniomaxillofacial surgeries for alleviating postoperative pain and edema. However, the studies evaluating their therapeutic effects on paresthesia have reported controversial results [28]. A controlled study by Seo et al. evaluated the effect of prednisolone administration (the related protocol is presented in Table 1), and the time of treatment starts on alleviating late paresthesia, reporting that prednisolone administration 3–6-week post-operation might accelerate the sensation recovery. Moreover, other corticosteroids were used during oral surgeries but showed no significant benefit [29]. Thus, there is a need for further studies with larger sample sizes and robust designs to evaluate the effect of corticosteroids on late paresthesia. However, the adverse effects of long-term corticosteroid use, including adrenal insufficiency, osteoporosis, and gastrointestinal, hepatic, and ophthalmologic impacts, should not be neglected [30].

Among the four studies evaluating the therapeutic effect of PBM, four studies showed its significant benefit compared to the control group even in the case of neurotmesis [1]. These findings are compatible with a meta-analysis by Firoozi et al. [31] that investigated the effect of preemptive PBM used during sagittal split ramus osteotomy on the recovery of postoperative NSDs. The meta-analysis included studies using PBM for 6–14 sessions and reported that 8–10 PBM sessions could accelerate the NSD recovery. However, the present systematic review found that more sessions of PBM, about 12–30 sessions, are needed for sensation improvement in late paresthesia.

Compared to surgical and medical therapies, PBM is a noninvasive therapeutic modality with no side effects. However, its application needs an operator. Moreover, the related treatment course is too time-consuming and needs several sessions. According to studies, PBM can alter the electrical activity and morphology of healthy and injured neurons in rats [16]. Also, it has shown beneficial effects in muscle and nerve repair and wound healing by accelerating cellular proliferation, improving local microcirculation, and reducing the inflammatory mediator release in the arachidonic acid pathway, which helps in stabilizing the neuronal membrane and reducing the transmission of pain sensation [1, 32].

Preemptive medical therapy to reduce the occurrence of postoperative paresthesia does not seem to be reasonable for several reasons. Firstly, the prescription of high-dose corticosteroids can result in adverse side effects. Additionally, multiple therapeutic sessions and the associated costs of PBM do not justify its use as a preemptive therapeutic approach. Therefore, it is advisable to wait at least 1 week following surgery to allow for the reduction of postoperative inflammation, confirm the presence of paresthesia, and then commence medical interventions [12, 33]. Furthermore, relying on close observation for spontaneous healing, a common practice, may not be ideal. Each month that passes without intervention reduces the likelihood of recovery by 5.8% [34]. Thus, it is recommended to initiate the aforementioned nonaggressive treatments, either alone or in combination, following the confirmed diagnosis of paresthesia 1-week post-surgery. This approach should take into account the patient’s underlying conditions, the affordability of the treatment, and the time the patient can dedicate to such therapies.

There is limited evidence evaluating surgical treatments for nerve injuries involving both the IAN and lingual nerves. The aggressiveness of these interventions correlates with the severity of the nerve damage. In cases of nerve damage suspected to be due to compression, decompression through internal and external neurolysis is performed by removing or releasing the surrounding tissues to alleviate the pressure. When the two ends of the nerve can reach each other without tension, direct neurorrhaphy is employed; otherwise, the sleeves technique is used. In instances of severely disrupted nerves, an autologous nerve graft, harvested from the greater auricular or medial antebrachial nerves, is utilized. This method is considered the gold standard despite its disadvantages, such as the requirement for a second surgical site [35, 36]. Surgical intervention is generally recommended if sensory recovery has not occurred within 3 to 9 months despite the application of the aforementioned noninvasive modalities [37]. More robust RCTs are needed in the field of surgical nerve damage treatment. These studies should consider the development of next-generation conduits enriched with stem cells, Schwann cells, and extracellular matrix proteins, which enable the controlled delivery of neurotrophic factors for guided nerve regrowth [36].

Finally, the included studies had a considerable amount of bias in several fields, including randomization, allocation concealment, blinding, and data analysis in case of study withdrawal by some patients (Fig. 2). Most studies only mentioned that they used randomization without giving further information on their way of randomization. However, based on the checklists of risk of bias assessment and Good Clinical Practice (GCP) guidelines, such information is not enough [38], and the randomization type (e.g., simple, block, stratified, and others) and related method or tool should be discussed in details. The method of allocation concealment (e.g., using opaque envelopes) should be explained in detail as well. Moreover, most studies only mentioned that they blinded the participants, researchers, or data analysis level, lacked a robust blinding setup, and did not give any further information on the method of maintaining the blinding chain during the study, its potential compromise, and related reasons. Also, the last field with the highest bias was the method of data analysis in case of study withdrawal by some patients. Ultimately, it is recommended to perform future studies addressing the mentioned shortcomings while following the GCP guidelines to achieve valid and reliable results.