Efficacy of low-level laser therapy and microsurgery on neurosensory recovery following inferior alveolar and lingual nerve injuries: A systematic review

Abstract

Purpose

This systematic review evaluates the relative effectiveness of low-level laser therapy (LLLT) and microsurgery for neurosensory recovery following sustained iatrogenic injuries to the inferior alveolar nerve (IAN) and lingual nerve (LN) more than 6 months in Oral and Maxillofacial surgery procedures.

Methods

Six articles were included. The mean age of microsurgery studies was 41.5 years and that of LLLT studies was 31.5 with female predominance in all studies. The majority of the included studies have been based on both subjective and objective assessments for neurosensory, two investigating microsurgery and four investigating LLLT following a Six-month post-IAN and LN injury.

Results

Each modality demonstrated positive outcomes in both subjective and objective assessments of neurosensory function. Notably, LLLT exhibited efficacy even when employed beyond a six-month interval following the initial injury. Early intervention is generally recommended, particularly for microsurgical approaches.

Conclusion

LLLT shows exciting promise as a minimally invasive approach for neurosensory rehabilitation even after six months of injury, while microsurgery studies revealed an improvement and the recommendation for early intervention post-nerve injury, the potential of LLLT and optimize its use for neurosensory rehabilitation, additional randomized controlled trials with larger sample sizes, longer follow-up periods, and blinding protocols are necessary.

1. Introduction

Due to their intimate interaction with the anatomical components of the mandible, injuries to the peripheral branches of the trigeminal nerve during surgery pose a serious risk in the field of Oral and Maxillofacial Surgery.¹ Thus, particular injury to the inferior alveolar nerve (IAN) and lingual nerve (LN) occurs during common Oral and Maxillofacial surgeries including local anaesthesia delivery, impacted third molar removal, Bilateral sagittal split osteotomy (BSSO), and dental implant placement.^{2, 3, 4}

Although many of these nerve injuries are very transient, patients might still experience serious concerns due to post-operative paresthesia and dysesthesia brought on by nerve damage.¹ While nerve regeneration typically takes several weeks to six months regardless of compression or less severe crush injuries, residual IAN damage has been documented after one year.⁵ These manifestations may have a significant impact on the patient's daily activities, such as consuming food and drink, and they can additionally result in traumatic biting of soft tissues while masticating, such as the lips or cheeks.^6,7

Even though it is known that the majority of accidental nerve damages recover on their own and the regeneration period of damaged nerve has been documented to occur from several weeks to 6 months spontaneously in the postoperative period,⁸ certain damage is unlikely to heal after 6 months elapsed since the injury, thereby rendering the surgeon with only a few therapeutic options, including medication therapy and micro neurosurgery, each of which is associated with various levels of efficacy and morbidity.^{9, 10, 11} There is a critical medical need for low-morbidity, high-success therapeutic techniques for the management of unintentional nerve injury to minimize the potential comorbidity of surgical therapy as well as the adverse responses of pharmaceutical medications.^{9, 10, 11} Microneurosurgery has been used as an effective therapeutic modality that has demonstrated favourable results.⁸ Low-level laser therapy (LLLT) has also been introduced as an effective non-invasive therapeutic modality with promising results of neurosensory recovery.¹² In this systematic review, we aimed to investigate the efficacy of low-level laser therapy and Microsurgery on neurosensory recovery following inferior alveolar and lingual nerve injuries.

2. Materials and methods

This systematic review was conducted based on the Preferred Reporting Items of Systematic Review and Meta-Analysis (PRISMA) and was registered on PROSPERO with the following ID: (CRD 42023393593).

Our PICO question is as follows: How do low-level laser therapy and microsurgery affect the neurosensory recovery of inferior alveolar and lingual nerve injury?

3. Population

• ●ASA Grade 1 and 2 human adult patients aged above 18 years.
• ●Patients who have undergone maxillofacial surgery procedures and undergone treatment in the form of Low-Level Laser therapy or Microsurgery for neurosensory recovery of inferior alveolar and lingual nerve injuries.
• ●Inferior alveolar nerve and lingual nerve neuropathies resulting from maxillofacial surgery procedures.
• ●Injury that lasts more than 6 months.

4. Intervention

• ●The use of Low-level laser therapy (LLLT) or Microsurgery therapy on injured Lingual nerve or inferior alveolar nerve following maxillofacial surgery procedures.

5. Comparison

• ●Placebo or the unaffected side as a control group.

6. Outcome

• •Subjective and objective assessment parameters like Visual analog scale or two-point discrimination, thermal stimuli, light touch, or pinprick tests.

The following inclusion criteria were applied:

Randomized clinical trials, prospective studies, retrospective studies, or case series.

The exclusion criteria were set as follows:

• -case reports, reviews, abstracts, language, incomplete outcome.
• -Lack of reporting on the evaluation method of IAN neuropathy.
• -No report on the laser irradiation conditions such as radiation wavelength and site of laser radiation.
• -Studies that performed the interventions in conjunction with any other treatment modalities or medications.
• -Inaccessible articles with full text.
• -Animal studies are excluded.

7. Search strategy

PubMed, The Cochrane Library, and EBSCO were independently searched. Gray literature was also searched for relevant information. Cross-referencing and citation searches were also conducted to find relevant articles. The search was limited to articles published in the English language only with no restriction in the year of publication.

The following search strategies have been used for the literature search: (Low level laser therapy) OR (LLLT)) OR (Superpulsed low level laser therapy)) OR (Laser Phototherapy)) OR (Biostimulation)) OR (Biostimulation laser)) OR (Laser Irradiation)) OR (Low-Level Light therapy)) OR (Photobiomodulation therapy)) OR (((Micro neurosurgery) OR (microsurgery repair)) OR (Microsurgical approach))) AND ((((((Nerve injury) OR (inferior alveolar nerve damage)) OR (lingual nerve damage)) OR (paresthesia)) OR (Neurosensory disturbance)) OR (Partial Nerve amputation))) AND ((((Neurosensory recovery) OR (Neurosensory deficit improvement)) OR (Neurosensory improvement)) OR (Sensory regeneration)).

8. Article selection process

Firstly, titles and abstracts of all papers retrieved based on the search strategy were checked = "checked" value = "1" for relevance. All those that were irrelevant were excluded. Those with unclear relevance were downloaded for eligibility assessment based on the pre-defined inclusion and exclusion criteria. Any disagreement between two individuals was resolved by the third reviewer who is much experienced in this clinical and research work. Rayyan software was used for article management. All data were recorded in an Excel spreadsheet.

9. Risk of bias assessment

The assessment of the risk of bias was done by two reviewers (TA) and (GA), to analyze the methodological quality of the articles included. The Cochrane Risk of Bias Tool for Randomized Controlled Trials was used. The tool assesses the random sequence generation, allocation concealment, selective reporting of data, other bias, blinding of participants and personnel, blinding of outcome assessment, and incomplete outcome data. The Newcastle-Ottawa scale was used for other studies (Cohort). A study with more than 6 stars and less than 6 stars on the Newcastle-Ottawa scale was a “low risk of bias” and “high risk of bias” study respectively.

10. Data extraction

The data collection process was done by two independent reviewers (GA) and (TA). The following data were extracted: study design; number of patients; patient age (mean or range); gender; medical and dental history; side of the mandible that caused the neurosensory deficit, nerve involved, time-lapse from the nerve injury to the date of the intervention, laser wavelength, radiation dosimetry and protocol, radiation area, results of the subjective and objective neurosensory tests.

11. Results

A total of 4233 articles were identified from the following databases Pubmed, EBSCO, and Cochrane. Then, duplicates were removed n = 14. After that, n = 4219 were screened with titles and abstracts. N = 4184 were excluded. A total of n = 35 was sought for retrieval. Out of these four articles could not be retrieved. N = 31 articles were assessed for eligibility. Out of this, 25 articles were excluded and the reason for exclusion is shown in Fig. 1. Finally, a total of n = 6 articles were included in this systematic review (As shown in Fig. 1).

Fig. 1.

PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only.

A total of six articles were included, two articles have investigated the microsurgery outcomes after nerve injury. Both articles were prospective studies of its design. While the other four articles have investigated the outcome of low-level laser therapy after nerve injury. With three studies being randomized clinical trials and one study cohort of its design.

The mean age of microsurgery studies was 41.5 and that of LLLT studies was 31.5 with female predominance in all studies. The type of surgery varied from third molar extraction,^{13, 14, 15, 16, 17,} cystectomy,¹⁴ mandibular sagittal split osteotomy^15,16 root canal treatment,^13,17 tongue overgrowth,¹⁷ and implants.¹⁴ Bilateral sides were mentioned by all the authors except the Pol et al. study.¹⁴ Most of the reported injured nerve was inferior alveolar nerve^{11,13, 14, 15, 16} with the lingual nerve being reported in only one study.¹⁷ The time elapsed since nerve injury was more than 6 months in all the studies (As shown in Table 1).

Table 1.

General characteristics of included studies.

Author and year	Study design	Number of patients	Age	Gender	Type of Surgery in which nerve injury occurred	Side	Injured nerve	Time elapsed from injury to intervention
Renato Pol,2016	RCT	19	Mean age 37	4 male, 15 females	Third molar, Implant, Cystectomy	No report	Inferior alveolar nerve	>6 months
Tuncer Ozen, 2006	case series	4	21–24	4 female	Third molar	Right, left	Inferior alveolar nerve	>1 year
SHELLEY M. KHULLAR,1996	RCT	13	35	4 men, 9women	Mandibular sagittal split osteotomy, surgical removal of impacted wisdom teeth and mandibular fracture	Bilateral and unilateral	Inferior alveolar nerve	>6 months
SHELLEY M. KHULLAR,1996	RCT	13	range of 20–55 years (mean, 35.7 years)	(4 men and 9 women)	Mandibular sagittal split osteotomy	Bilateral and unilateral	Inferior alveolar nerve	>2 years
PETER G,1984	Case series	3	Mean 42	2 women, 1 man	Third molar, root canal treatment, tongue overgrowth	Variation	Lingual nerve	Variation
Hillerup S,2008	Cohort	48	Median 41	40 females, 12 males	Third molar, root canal treatment, implant	Left side, bilateral	Inferior alveolar nerve	>6 months

In LLLT studies, the minimum and maximum duration of sessions was 20 and 69 days respectively. Most of the reported studies have used laser wavelengths of 820.^11,15,16 However, a wavelength of 904–910 was reported by one study.¹⁴ Majority of the studies have used GaAIAs laser protocol^11,15,16 while another study has used GaAs diode laser.¹⁴ (As shown in Table 2). The minimum follow-up period of the cases was two months^14,16 with the majority of the cases being followed up for 12 months and more.^13,15,17 (As shown in Table 2),

Table 2.

Details of treatment and outcome parameter.

Author and year	treatment modality	laser wavelength	duration	dosimetry &protocol	follow up	Result	Conclusion
Renato Pol, 2016	LLLT	904–910	10 sessions	GaAs diode laser	Up to 10 weeks	A statistical significant difference (P = 0.0340) in VAS postoperatively. A recovery was observed in patients with permanent paresthesia (>6 months) (P < 0.05).	Positive neurosensory improvement in patient with inferior alveolar nerve paresthesia
Tuncer Ozen, 2006	LLLT	820-to-830	39 days	Plus GaAlAs diode	Mean 13.5	A significant improvement in the assessment of the degree of neurosensory deficit (p = 0,02). A statistical significant improvement in the brush stroke directional discrimination test for fine touch and direction sense (p = 0.01).	Positive subjective and objective improvement in long standing neurosensory deficit.
SHELLEY M. KHULLAR, 1996	LLLT	820	36–69 days.	GaAIAs laser	Up to 63 days	A significant improvement in mechanoreceptor sensory testing subsequent to laser treatment (P = 0.01).	Positive improvement of mechanoreceptor perception in long-standing neurosensory deficit of IAN
SHELLEY M. KHULLAR, 1996	LLLT	820	20–63 days	GaAIAs	2 years	A positive significant improvement in the subjective assessment lip (p = 0.01) and chin (p = 0.02). Furthermore, a significant decrease in the area of mechanoperception neurosensory deficit (p = 0.01)	Positive subjective and objective improvement of neurosensory deficit
PETER G. MOZSARY, 1984	Microsurgeery	NA	NA	NA	Up to one year	sensation recovery was observed at 5 months postoperatively while full sensation recovery was observed at 9 months.	Nerve repair can be carried out successfully after more than a year.
Hillerup S.2008	Microsurgery	NA	NA	NA	12 months	A positive significant improvement in two-point discrimination thresholds was observed (p < 0.001.)	Favourable neurosensory recovery after microsurgery repair

The parameters used for nerve deficit assessment have included both subjective and objective assessment. The objective assessment has varied among the studies with pin brick, fine touch discrimination, directional discrimination, and thermal test being the predominant among the included studies.

LLLT has shown a statistically significant difference (p = 0.0340) in the visual analog scale postoperatively.¹⁴ A recovery was observed in patients with permanent paresthesia (>6 months) (p < 0.05).¹⁴ Furthermore, a significant improvement was reported in the assessment of the degree of neurosensory deficit (p = 0.02).¹¹ A statistically significant improvement in the brush stroke directional discrimination test for fine touch and direction sense was observed (p = 0.01).¹¹ A significant improvement in mechanoreceptor sensory testing after laser treatment was found (p = 0.01).¹⁵ A positive significant improvement was seen in the subjective assessment of lip (p = 0.01) and chin (p = 0.02).¹⁶ Additionally, a significant decrease in the area of mechanoperception neurosensory deficit was identified (p = 0.01).¹⁶

The findings of LLLT studies revealed an improvement in subjective and mechanoreceptor neurosensory function with no improvement in thermoception reported.^{14, 15, 16} (As shown in Table 2).

The findings of microsurgery studies have shown A positive significant improvement in two-point discrimination thresholds was observed (p < 0.001.).¹³ In addition a recommendation for early intervention has been emphasized. Nevertheless, repair can be performed even after one year of injury with improvement.^13,17(As shown in Table 2).

For risk of bias assessment, the Cochrane risk of bias tool and Newcastle Ottawa scale were used for clinical trials and observational studies respectively.

Firstly, for randomized controlled trials risk of bias was assessed based on the ROB 2.0 tool.

The following categories were used for the risk of bias in the included studies:

• 1.Low risk (plausible bias unlikely to seriously alter the results) if all criteria were met;
• 2.Moderate risk (plausible bias that raises some doubt about the results) if one or more criteria were partly met; or
• 3.High risk (plausible bias that seriously weakens confidence in the results) if one or more criteria were not met.

Most of the included studies were addressed as 'low risk of bias', except in the category of random sequence generation (selection bias) and Allocation concealment (selection bias) which was to a certain extent based on the inadequate reporting of the criteria that are a prerequisite in the evaluation of methodological rigour in terms of trial design and conduct (As shown in Fig. 2).

Fig. 2.

Shows ROB assessment scale.

Secondly, among three observational studies, one study by Hillerup et al.,¹³ scored 6 on the Newcastle Ottawa scale thus showing a low risk of bias whereas the other two studies scored less than 6 showing a high risk of bias. (As shown in Table 3).

Table 3.

Newcastle ottawa quality assessment scale.

Study	Representativeness of exposed	Selection of non exposed	Ascertainment of exposure	Outcome of interests not present at time of exposure	Comparability	Assessment of outcome	Follow up long enough for outcome to happen	Adequacy of f/u	Total
S. Hillerup, 2008		*	*	*		*	*	*	6
PETER G., 1984			*	*		*	*	*	5
Tuncer Ozen, 2006			*	*		*		*	4

12. Discussion

This systematic review was set out with the aim of investigating the neurosensory recovery of inferior alveolar and lingual nerve injuries following LLLT and microsurgery interventions. Various nerve injuries might occur during routine oral and maxillofacial surgeries such as stretching, crushing, compression, and partial or complete nerve section.¹⁴

Thus, such injuries might result in neurosensory impairment that could be of temporary period or sustained injuries that require interventions.^1,18,19 Although no consensus statement in the literature about the uniform way of neurosensory testing, the majority of the included studies have been based on both subjective and objective assessments for neurosensory testing.^{14, 15, 16, 17}

The studies revealed neurosensory improvement in subjective assessment based on the visual analogue scale.^14,15 In addition, studies reported a significant mechanoreceptor improvement with no significant difference in thermoreceptor testing.^14,15

Nerve injury management during the first three months is not usually recommended due to the high potential for spontaneous nerve recovery during this time.²⁰ Furthermore, the focus on alleviating symptoms and enhancing recovery time by pharmacological approach including anti-inflammatory and vitamin B complex has been recommended.¹² On the other hand, sustained injury of more than 6 months usually requires various interventions for neurorehabilitation.²⁰

LLLT has been documented as a non-invasive approach to neurorehabilitation.¹² The main function of LLLT is to reduce inflammation, reduce pain, and enhance nerve tissue repair.²¹ The hypothesis behind nerve tissue repair in LLLT is light absorption by the injured nerve. Thus, altering its metabolism by producing growth-associated proteins, myelinization, and inflammatory cytokines modulators. In addition, it might aid in the reinnervation of non-injured nerves.^14,22

Two of the reported studies have sustained an injury of more than 6 months at the intervention application.^14,16 While one study has reported a sustained injury of more than a year and another of more than 2 years.^14, The results of these studies have revealed an improvement at this time.^14,15 However, this is in contrast with other studies that have emphasized early intervention.²³ Those studies have reported 90–100 % neurosensory improvement when intervention was applied within two days postoperatively but the limitation was reported to have a lack of accuracy of this improvement as the spontaneous nerve repair occurs during this period.^14,23,24

One of the included studies has revealed an insignificant difference between injuries of less than 6 months and injuries of more than 6 months regarding objective measurement.¹⁴ In addition, they found that recovery in patient sensitivity with sustained injuries more than 6 months is similar to those injuries less than 6 months.¹⁴ The nerve injury and wound healing varies based on several factors.^15,25

Furthermore, Ozen et al., have reported a positive mechanoreceptor improvement in neurosensory function after LLLT application in patients who sustained nerve injury for more than one year.¹¹ This is consistent with the findings of Khullar et al., in two of their studies which also reported a subjective improvement.^15,16 Mirzaei et al., have reported a similar finding concerning positive subjective and objective improvement after sagittal split osteotomy.²⁵ In another Cochrane review by Coulthard et al., he reported a mean change of neurosensory deficit of 8.40 cm at the chin area and 21.79 cm at the lip area.²⁶ The laser wavelength has been documented to play a crucial role in the successful treatment of LLLT as a proper dose of light penetration to the tissue has a positive effect on nerve regeneration.²⁷

Most of the studies included in this systematic review have used GaAIAs laser with a wavelength of 820 nm.^15,16 On the other hand, one randomized clinical trial has used 904–910 nm wavelength.¹⁴ This is in line with evidence supporting that 800–980 nm wavelength has the potential of greater efficiency than those with red spectral region.^{28, 29, 30} Mohajerani et al., have investigated the neurosensory recovery after sagittal split osteotomy and they reported that a combination of 810 nm and 632 nm has produced a positive effect on neurosensory recovery.²⁹

Similarly, Pol et al., have reported an improvement in neurosensory recovery in combined super pulse 904 nm and continuous 650 nm.¹⁴ Lima et al., have mentioned the addition of infrared red light to enhance the deep penetration of tissues.³¹ Although no consensus statement regarding the proper dose of LLLT, most of the unfavourable outcomes are due to less dosimetry rather than more dosimetry. Owing to the fact of achieving a high number of mitochondria which is located deeply in the tissues, a proper dose is recommended to overcome the attenuation by superficial tissues.³¹

Furthermore, several studies have applied extra-oral and intra-oral laser radiation approaches to achieve proper attenuation to the deep tissues.³¹

Although no consensus statement in the literature about the uniform way of neurosensory testing, the majority of the included studies have been based on both subjective and objective assessments for neurosensory testing.^{14, 15, 16} For subjective assessment, the visual analog scale has been considered the gold standard.³² For the objective assessment, several tests have been documented in the literature such as the pinprick test which utilizes a dental probe to pinch the skin, the light touch utilizes cotton swabs to touch the skin, and the thermal test utilizes a Thermostat device.³² The studies revealed neurosensory improvement in subjective assessment based on the visual analogue scale.^{14, 15, 16} In addition, studies reported a significant mechanoreceptor improvement with no significant difference in thermoreceptor testing.^{14, 15, 16}

Microsurgery has been used for the treatment of nerve injury by the following options 1) decompression (scar excision) of the nerve, 2) nerve anastomosis, or 3) grafting.¹⁷ Neurosensory recovery has been documented to vary among different microsurgery procedures, nerve decompression has neurosensory recovery within weeks postoperatively and is documented to be completed within two to three months.¹⁷ while, in neurorrhaphy cases, recovery initiated within three to four months and got completed within six to 12 months.¹⁷ It has been documented that more favourable results have been associated with early treatment timing when it is within six months after the trauma.¹⁷ While, a delayed or partial recovery in cases with longer time since the injury has been observed.¹³

Early intervention for nerve repair has been recommended if dense scarring is evident or nerve continuity is interrupted. However, a repair can be accomplished, after more than a year.¹⁷ Also in another study one patient underwent a microsurgical nerve suture and recovered favourably and two of three patients responded favourably to nerve decompression.¹³

The limitation of the present systematic review could be the limited number of well-conducted randomized control trials and the heterogeneity of the data that limits the quantification of the study to draw a statistical conclusion. Further randomized control trials investigating the non-invasive approach for neurosensory rehabilitation including Low level laser therapy and Microsurgery are warranted.

13. Conclusions

Inferior alveolar and lingual nerve injuries are not uncommon in routine oral and maxillofacial surgery procedures. Different interventions are utilized to enhance nerve recovery that has been sustained for more than 6 months. The evidence from this study supports the use of Low Level Laser Therapy as a non-invasive procedure and it can be considered as a first choice of treatment for all nerve injuries. Microsurgical repair should be kept as the final option for those cases which are not resolved completely by Low Level Laser Therapy. However, caution should be taken for any certain conclusion as a limited number of studies were included due to strict inclusion criteria. Good quality clinical trials to assess the effectiveness of Low Level Laser Therapy and microsurgery are highly recommended.

Source of funding

None.

Ethical clearance statement

This is a systematic review –which was started in the year 2023. No funding has been taken from the institution. And hence no ethical clearance was done as there is no involvement of any clinical work here.

Patient/guardian consent

This is a review article. No patients are contacted for any reason. So no consent form is required.

Source of funding statement

This study has been funded by Deanship of Graduate studies and scientific research of Qassim University.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.