Effect of low-level laser therapy on nerve regeneration in median nerve-injured rats
Main Article Content
Abstract
Background
Median nerve injury can result in persistent sensory and motor deficits despite surgical repair. Low-level laser therapy (LLLT) promotes neuroregeneration through photobiomodulation; however, evidence in median nerve injury models remains limited. This study evaluated the effect of LLLT on functional and molecular recovery following median nerve injury in Wistar rats.
Methods
A randomized controlled study was conducted using twelve Wistar rats assigned to control (n=6) and LLLT (n=6) groups. A standardized median nerve crush injury was induced under anaesthesia. LLLT was initiated on day 1 post-injury and administered six days per week for three weeks, while the control group recovered without treatment. Functional recovery was assessed using grooming, rotarod, von Frey, and hot plate tests. Gene expression was analyzed using RT-PCR. Independent T-test and Two-way repeated-measures ANOVA was applied for rotarod, von Frey and hot plate outcomes, while grooming scores were analyzed using Mann–Whitney U tests.
Results
Between-group comparisons of grooming scores using the Mann–Whitney U test showed no statistically significant differences after Bonferroni correction. Independent-samples t-tests demonstrated significantly greater improvement in the low-level laser therapy group than the control group at Day 14 and post-intervention for the von Frey, rotarod, and hot plate tests (p<0.05). Two-way repeated-measures ANOVA demonstrated significant time, treatment, and time × treatment interaction effects for all three outcome measures (p<0.05).
Conclusion
Low-level laser therapy enhanced functional and molecular recovery after median nerve injury, supporting its potential as a non-invasive adjunct for peripheral nerve regeneration.
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References
1. Robinson LR. Traumatic injury to peripheral nerves. Muscle Nerve 2022;66:661-70. doi: 10.1002/mus.27706.
2. Tan RES, Jeyaratnam S, Lim AY. Updates in peripheral nerve surgery of the upper extremity: diagnosis and treatment options. Ann Transl Med 2023;11:391. doi: 10.21037/atm-23-1500.
3. Khan H, Perera N. Peripheral nerve injury: an update. Orthop Trauma 2020;34:168-73. doi: 10.1016/j.mporth.2020.03.011.
4. Zhai X, Wang Y. Physical modulation and peripheral nerve regeneration: a literature review. Cell Regen 2024;13:32. doi: 10.1186/s13619-024-00215-9.
5. Tapp M, Wenzinger E, Tarabishy S, Ricci J, Herrera FA. The epidemiology of upper extremity nerve injuries and associated cost in the US emergency departments. Ann Plast Surg 2019;83:676-80. doi: 10.1097/SAP.0000000000002083.
6. Padovano WM, Dengler J, Patterson MM. Incidence of nerve injury after extremity trauma in the United States. Hand 2022;17:615-23. doi: 10.1177/1558944720963895.
7. Murphy KA, Ryan N, Fakoya AO. Anatomy, shoulder and upper limb, median nerve. StatPearls: Treasure Island;2025.
8. Theofilopoulou S, Katouni K, Papadopoulos V, et al. Variations of the median nerve and carpal tunnel syndrome: a systematic review of the literature. Maedica (Bucur) 2023;18:699-704. doi: 10.26574/maedica.2023.18.4.699.
9. Prabakaran L, Vedakumari SW, Pravin YR. Natural polymeric biomaterials for managing peripheral nerve injuries: a novel approach for tissue repair and reconstruction. Neurosurg Rev 2024;47:805. doi: 10.1007/s10143-024-03025-4.
10. Maghimaa M, Bharath S, Kandasamy S. Carbon-based nanoparticles for neural regeneration. In: Nanoparticles in modern neurological treatment. Sivamaruthi BS, Sisubalan N, Kesika P, Varaprasad K, editors. Springer Cham Switzerland; 2025. pp. 263-82. doi: 10.1007/978-3-031-80185-3_10.
11. Kaluskar P, Bharadwaj D, Iyer KS, Dy C, Zheng M, Brogan DM. A systematic review to compare electrical, magnetic, and optogenetic stimulation for peripheral nerve repair. J Hand Surg Glob Online 2024;6:722-39. doi: 10.1016/j.jhsg.2024.03.005.
12. Tuffaha S, Lee EB. Growth factors to enhance nerve regeneration: approaching clinical translation. Hand Clinics 2024;40:399-408. doi: 10.1016/j.hcl.2024.04.002.
13. Li A, Pereira C, Hill EE, Vukcevich O, Wang A. In vitro, in vivo and ex vivo models for peripheral nerve injury and regeneration. Current Neuropharmacol 2022;20:344-61. doi: 10.2174/1570159X19666210407155543.
14. Gordon T. Electrical stimulation to enhance axon regeneration after peripheral nerve injuries in animal models and humans. Neurotherapeutics 2016;13:295-310. doi: 10.1007/s13311-015-0415-1.
15. Wang CZ, Chen YJ, Wang YH, Yeh ML, Huang MH, Ho ML. Low-level laser irradiation improves functional recovery and nerve regeneration in sciatic nerve crush rat injury model. PLoS One 2014;9:e103348. doi:10.1371/journal.pone.0103348.
16. Alharbi G, Rao JK, Alnaim T, Alzamil N. Efficacy of low-level laser therapy and microsurgery on neurosensory recovery following inferior alveolar and lingual nerve injuries: a systematic review. J Oral Biol Craniofac Res 2024;14:631-7. doi: 10.1016/j.jobcr.2024.08.006.
17. Rosso MP, Buchaim DV, Kawano N, Furlanette G, Pomini KT, Buchaim RL. Photobiomodulation therapy (PBMT) in peripheral nerve regeneration: a systematic review. Bioengineering 2018;5:44. doi: 10.3390/bioengineering5020044.
18. Ma Y, Yang M, Chen X, Qu W, Qu X, He P. The effectiveness of photobiomodulation therapy on inferior alveolar nerve injury: a systematic review and meta-analysis. PLoS One 2023;18:e0287833. doi: 10.1371/journal.pone.0287833.
19. Buzza AS, Cousins H, Tapas KE, et al. Direct photobiomodulation therapy on the sciatic nerve significantly attenuates acute nociceptive sensitivity without affecting motor output. Neuromodulation 2024;27:1338-46. doi: 10.1016/j.neurom.2024.04.011.
20. Kongsui R, Surapinit S, Promsrisuk T, Thongrong S. Pinostrobin from Boesenbergia rotunda attenuates oxidative stress and promotes functional recovery in rat model of sciatic nerve crush injury. Braz J Med Biol Res 2023;56:e12578. doi: 10.1590/1414-431X2023e12578.
21. Percie du Sert N, Hurst V, Ahluwalia A, et al. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. J Cereb Blood Flow Metab 2020;40:1769-77. doi: 10.1177/0271678X20943823.
22. Ashok V, Ganesh MK, Maiti S, Nallaswamy D, Heboyan A. Evaluation of 3D-printed polylactic acid as a bone substitute: an animal study in a rat model. Clin Exp Dent Res 2025;11:e70201. doi: 10.1002/cre2.70201.
23. Fellin CR, Steiner RC, Buchen JT, Anders JJ, Jariwala SH. Photobiomodulation and vascularization in conduit-based peripheral nerve repair: a narrative review. Photobiomodul Photomed Laser Surg 2024;42:1-10. doi: 10.1089/photob.2023.0103.
24. Underwood W, Anthony R. AVMA guidelines for the euthanasia of animals. American Veterinary Medical Association : Schaumburg, IL ; 2020.
25. Deuis JR, Dvorakova LS, Vetter I. Methods used to evaluate pain behaviors in rodents. Front Mol Neurosci 2017;10:284. doi: 10.3389/fnmol.2017.00284.
26. Shan HM, Maurer MA, Schwab ME. Four-parameter analysis in modified Rotarod test for detecting minor motor deficits in mice. BMC Biol 2023;21:177. doi: 10.1186/s12915-023-01679-y.
27. Teixeira RK, Calvo FC, Santos DR, et al. Criteria for assessing peripheral nerve injury. Behavioral and functional assessment in non-operated Wistar rats. Acta Cir Bras 2020;35:e202000702. doi: 10.1590/s0102-865020200070000002.
28. Ling R, Wang Y, Zheng W, et al. Effects of different types of neonatal pain on somatosensory and cognitive development in male juvenile rats. Brain Behav 2023;13:e3309. doi: 10.1002/brb3.3309.
29. Chen Z, Halford NG, Liu C. Real-time quantitative PCR: primer design, reference gene selection, calculations and statistics. Metabolites 2023;13:806. doi: 10.3390/metabo13070806.
30. Chacur M, Rocha IR, Harland ME, et al. Prevention and reversal of neuropathic pain by near-infrared photobiomodulation therapy in male and female rats. Physiol Behav 2024;286:114680. doi: 10.1016/j.physbeh.2024.114680.
31. Uta D, Ishibashi N, Konno T, et al. Near-infrared photobiomodulation of the peripheral nerve inhibits the neuronal firing in a rat spinal dorsal horn evoked by mechanical stimulation. Int J Mol Sci 2023;24:2352. doi: 10.3390/ijms24032352.
32. Andreo L, Ribeiro BG, Alves AN, et al. Effects of photobiomodulation with low‐level laser therapy on muscle repair following a peripheral nerve injury in Wistar rats. Photochem Photobiol 2020;96:1124-32. doi: 10.1111/php.13255.
33. Bayburt KA, Diker N, Aydin MS, Dolanmaz D. The effect of high-intensity versus photobiomodulation therapy (PBM) on the regeneration of the sciatic nerve following crush injury: an animal study. Lasers Med Sci 2025; 40:81. doi: 10.1007/s10103-025-04334-w.
34. Forootan KS, Forghani SF, Madani SP, Estahbanati HK, Forootan NS. Laser therapy after repair of the distal half of the median nerve: a comparative study. Trauma Mon 2015;20:e23816. doi: 10.5812/traumamon.20(2)2015.23816.
35. Alcantara CC, Gigo-Benato D, Salvini TF. Effect of low-level laser therapy (LLLT) on acute neural recovery and inflammation-related gene expression after crush injury in rat sciatic nerve. Lasers Surg Med 2013;45:246-52. doi: 10.1002/lsm.22129.
36. Shen CC, Yang YC, Huang TB, Chan SC, Liu BS. Low-level laser-accelerated peripheral nerve regeneration within a reinforced nerve conduit across a large gap of the transected sciatic nerve in rats. Evid Based Complement Alternat Med 2013;2013:175629. doi: 10.1155/2013/175629.
37. Siva S, Ramana K, Suganthirababu P, et al. Effectiveness of low level laser therapy and low intensity pulsed ultrasound on neurotrophic factors in experimentally induced peripheral nerve injury Wistar rat: a systematic review. Indian J Physiother Occup Ther 2024;18:164-9. doi:10.37506/yry6ya09.