The effect of high-intensity versus photobiomodulation therapy (PBM) on the regeneration of the sciatic nerve following crush injury: an animal study

Laser therapy is a non-invasive method that supports tissue regeneration and has a wide range of applications [25]. Photobiomodulation therapy (PBMT) is particularly effective in musculoskeletal disorders and nerve injuries. Studies in the literature have demonstrated that the biostimulatory effects of PBMT increase myelin sheath thickness, promote Schwann cell proliferation, and exert positive effects on neurotrophic growth factors [9,10,11].

High-intensity laser therapy (HILT) has emerged as an alternative method to PBMT by delivering stronger energy applications. The advantages of HILT include deeper tissue penetration, shorter treatment duration, and higher energy doses. These features facilitate tissue regeneration, improve local blood circulation, and enhance thermal and mechanical effects [15, 26].

Moreover, HILT induces electromagnetic fields, photoelectric changes, and electrochemical reactions in target tissues, contributing to pain and edema reduction [20, 21]. This study aims to investigate the effects of HILT on sciatic nerve regeneration following crush injury and to fill this critical gap in the literature.

Literature reviews indicate successful outcomes in studies involving low-level lasers. Khullar et al. [27] demonstrated the effects of low-level laser therapy (GaAlAs 830 nm, 6 J) on nerve regeneration following axonotmesis, with daily applications over 28 days. The PBMT group exhibited improved functional recovery of the nerve. Similarly, Gomes et al. [28] used a low-intensity laser with a wavelength of 660 nm and a dose of 3.84 J/cm², applied for 5 min daily over 21 days. Histomorphometric evaluations revealed that tissue regeneration in the laser-treated group was both qualitatively and quantitatively superior to the placebo group.

The aim of our experimental study was to evaluate the effects of HILT (High-Intensity Laser Therapy) on sciatic nerve regeneration in rats following crush injury and to compare its efficacy with PBMT (Photobiomodulation Therapy).

On postoperative days 14 and 21, the Sciatic Functional Index (SFI) demonstrated better recovery in the HILT group compared to the PBMT group (Table 2 ; Fig. 2). Electromyography (EMG) was analyzed to confirm the reinnervation of distal motor units. The data revealed no statistically significant differences in amplitude values among the HILT, PBMT, and control groups. However, latency and duration parameters were significantly higher in the PBMT group compared to the control and HILT groups (Table 2 ; Fig. 3) .

In the HILT group, the percentage of nerve fibers within the optimal g-ratio range (0.55–0.69) was higher, while the percentage in the suboptimal range (0–0.49) was lower compared to the other groups, indicating better myelination. The PBMT group exhibited a relatively higher number of Schwann cells, which was statistically different from the other groups. This suggests that the excessive number of Schwann cells in the PBMT group reflects ongoing degeneration, while the lower axon count within the optimal g-ratio range indicates delayed regeneration. In contrast, the HILT group demonstrated a lower number of Schwann cells and a higher axon count within the optimal g-ratio range, suggesting an accelerated regeneration process (Fig. 5). Consistent with findings from the Sciatic Functional Index, electromyography, and histopathological examinations, it can be hypothesized that HILT treatment may enhance nerve regeneration by delivering a high amount of energy to deep tissues in a short period through stronger laser beams.

The effects of high-intensity laser therapy (HILT) may stem from its ability to regulate the cytoskeletal network, contributing to tissue regeneration and repair. This therapy positively influences endothelial cell functions by increasing extracellular matrix and fibronectin production by connective tissue cells [21]. The limited number of studies using HILT has resulted in a restricted understanding of the treatment. Some preliminary research has shown that HILT is more effective than LLLT due to its higher intensity and the ability of the laser to penetrate deeper. The findings from our study on nerve regeneration support previous studies conducted in other fields.

The literature contains numerous studies examining the wavelength, dosage, application duration, and session intervals in laser treatments. However, in studies focusing solely on laser parameters, it remains unclear whether the primary influencing factor is wavelength or energy. The effectiveness of the treatment also depends on other factors, such as power, dosage, and laser type. Additionally, the expected regeneration time varies based on the type of injury, the nerve being studied, and the species examined [29], making it challenging to compare treatment protocols across studies.

The regenerative effects of different wavelengths in low-intensity laser therapy have been investigated in several studies. Barbosa et al. [30] compared the effects of low-power GaAlAs lasers (660 nm and 830 nm) on sciatic nerve regeneration following crush injuries, applied for 21 consecutive days. On the 14th postoperative day, the 660 nm group showed significant differences compared to the sham and 880 nm groups. They concluded that the 660 nm GaAlAs laser promoted early functional nerve recovery compared to the other groups. In contrast, Diker et al. [24] examined the therapeutic effects of 660 nm and 880 nm GaAlAs lasers (2.7 J/session) on inferior alveolar nerve (IAN) regeneration following crush injury. Laser therapy was initiated immediately after surgery and applied every 3 days for 30 days. Their findings indicated that the 880 nm wavelength, with its higher tissue penetration capacity, was more effective for biostimulation of the IAN after injury. These studies highlight contradictory findings regarding the optimal wavelength for nerve regeneration. The variations in results are attributed to differences in laser energy, techniques, and application durations.

Additionally, studies have investigated the tissue penetration capabilities of lasers with different wavelengths. Takhtfooladi and Sharifi examined the effects of 680 nm PBMT, 650 nm red LED, and 450 nm blue LED treatments on nerve regeneration after end-to-end suturing of the severed sciatic nerve over 14 days. They reported a higher number of total neurons, myelinated axons, and Schwann cells in the low-intensity laser group compared to the other groups [31]. The study concluded that a high-intensity laser with a wavelength of 1064 nm was more effective than a low-level laser with a wavelength of 650 nm. This finding suggests that lasers with longer wavelengths, offering higher tissue penetration capacity, may be more advantageous for biostimulation following nerve injury.

In the literature, it has been reported that the amount of energy applied in laser biostimulation treatments may influence healing effectiveness. Marcolino et al. [32] compared the regenerative effects of 10 J/cm², 40 J/cm², and 80 J/cm² of AsGaAl laser (830 nm) over 21 consecutive days following a sciatic nerve crush injury. They observed enhanced functional recovery on the 7th postoperative day in the 40 J/cm² laser irradiation group compared to the sham group. Additionally, on the 14th postoperative day, both the 40 J/cm² and 80 J/cm² laser irradiation groups demonstrated better outcomes compared to the sham group, while no differences were noted among the sham, 10 J/cm², 40 J/cm², and 80 J/cm² groups on the 21st postoperative day. The study concluded that PBMT at fluencies of 40 J/cm² and 80 J/cm² had a positive effect on accelerating functional nerve healing. In the present study, HILT was administered with a radiant energy of 120 J per session, while PBMT was administered with a radiant energy of 2.4 J per session. However, our results showed that HILT was more effective than PBMT.

There are numerous studies on the application of laser treatments. However, there is no established protocol. One study reported that 20 sessions over a total period of 3 months would be sufficient for treating IAN injury in humans [33]. In many nerve regeneration studies on rats following axonotmesis injury, it has been noted that functional recovery occurs between 4 and 8 weeks [34]. Therefore, in this study, to observe the bioconcentration and regenerative effects on crush-type injury in the sciatic nerve, irradiation with HILT and PBMT was administered 3 days a week for a total of 10 sessions.

In the literature comparing HILT and LLLT, Alayat et al. [35] investigated and compared the effects of high-intensity laser therapy (HILT) and low-level laser therapy (LLLT) in the treatment of patients with Bell’s palsy. The results indicated that both HILT and LLLT are effective physical therapy modalities for the recovery of Bell’s palsy patients, with HILT showing a slightly greater improvement than LLLT. Similarly, Kheshi et al. [36] compared the effects of LLLT and HILT on pain relief and functional improvement in patients with knee osteoarthritis. Their findings revealed that HILT combined with exercises was more effective than LLLT combined with exercises, and both treatments were superior to exercise alone for managing knee osteoarthritis.

A limitation of this study is the lack of evaluation of the heat induced during PBMT (Photobiomodulation Therapy) application. Accurately modeling temperature changes in in vivo studies is challenging. In the literature, Capon et al. [37] have reported that lasers transmit energy to surrounding tissues in the form of heat, creating a temperature gradient of 45–50 °C in adjacent tissues, regardless of the type of laser used. During the wound healing process, this temperature increase is suggested to result from the response of viable cells and to induce a heat shock response (HSR) by causing temporary changes in cellular metabolism due to the supra-physiological heat. This phenomenon is associated with the production of proteins known as HSPs (Heat Shock Proteins). However, the study by Wang et al. [38] demonstrated that the heat generated by laser-tissue interaction does not lead to significant changes in hemodynamic and metabolic effects. Additionally, the generalizability of the crush injury model used in this study is limited. Further controlled clinical studies are needed to investigate the effects of different types of nerve injuries, the underlying mechanisms of regeneration, and the impact of laser parameters. Finally, many previous studies have not adequately defined critical parameters of laser irradiation, such as dose, power, irradiation duration, and application method. This lack of standardization complicates comparisons between studies and contributes to inconsistent findings.

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