Table 3.
Characteristics of the included studies outcomes, light source parameters and combination treatment, in experimental studies
| Author | Disease category | Disorder | Species | Sex/Age | Combination therapy | Laser | Treatment duration | Key outcomes |
|---|---|---|---|---|---|---|---|---|
| Salehpour et al., 2019 [96] | Neuropsychiatric | Depression | BALB/c mice | M / Adult | CoQ10 | 810 nm, 33.3 J/cm2, 6.66 W/cm2 | 5 days |
Antidepressant-like effects; Decreased lipid peroxidation, corticosterone, TNF-α, and IL-6; Enhanced total TAC, GSH levels, GPx and SOD activities in HIP and PFC; The inflammatory response in the HIP and PFC was suppressed, as indicated by decreased NF-kB, p38, and JNK levels; Down-regulated intrinsic apoptosis biomarkers, BAX, Bcl-2, cytochrome c release, and caspase-3 and -9 |
| Meynaghizadeh-Zargar et al., 2020 [97] | Neuropsychiatric | Chronic mild stress | BALB/c mice | M / 8 weeks | Methylene blue | 810 nm, 8 J/cm2, 4.75 W/cm2 |
4 weeks (3/week) |
Anxiolytic effects; Therapeutic effects on mitochondrial dysfunction, learning and memory impairments; Decreased serum cortisol levels, NO production, ROS production, SOD; Increased TAC, GPx |
| Farazi et al., 2022 [98] | Neuropsychiatric | Depression | BALB/c mice | M / Adult | Environmental enrichment | 810 nm, 8 J/cm2, 4.75 W/cm2 | 14 days | Antidepressant-like effects; Up-regulated hippocampal BDNF/TrkB/CREB signaling pathway |
| Moges et al., 2009 [99] | Neurodegenerative | Amyotrophic lateral sclerosis | G93A SOD1 Transgenic mice | NM / 51 days | Riboflavin | 810 nm, 12 J/cm2 | (3/week) | The lack of significant improvement in survival and motor performance indicates interventions were ineffective in altering disease progression |
| Lapchak et al., 2008 [100] | Ischemia | Embolic stroke model | New Zealand white rabbits | M / NM | Tissue plasminogen activator | 808 nm, 10 mW/cm2 | NM | Near-infrared laser therapy may be administered safely either alone or in combination with tPA because neither treatment affected hemorrhage incidence or volume |
| Li et al., 2014 [101] | Ischemia | Hypoxic-ischemic brain damage | Sprague–Dawley rats | M, F / 3 months | Mesenchymal stem cell | 660 nm, 60 mW/cm2 | 7 days | Diode irradiation promotes migration of the transplanted bone marrow mesenchymal stem cells |
| Salehpour et al., 2019 [102] | Ischemia | Ischemia | BALB/c mice | M / Adult | CoQ10 | 810 nm, 33.3 J/cm2, 6.66 W/cm2 | 14 days | Improved spatial and episodic memory; Lowered ROS levels; Increased ATP and general mitochondrial activity as well as biomarkers of mitochondrial biogenesis including SIRT1, PGC-1α, NRF1, and TFAM; Decreased inflammatory responsiveness, iNOS, TNF-α and IL-1β levels |
| Menovsky et al., 2003 [103] | Nerve injury | Sciatic nerve crush | Wistar rats | M | Solder and suture materials | CO2 laser | NM | Leads to optimal early histological results and least foreign-body reaction at the repair site |
| Duke et al., 2012 [104] | Nerve injury | Sciatic nerve crush | Sprague–Dawley rats | M | Electrical stimulation | 1875 nm | NM | Reduces the laser power requirements and mitigates the risk of thermal damage while maintaining spatial selectivity |
| Dias et al., 2013 [105] | Nerve injury | Sciatic nerve crush | Wistar rats | M | Natural latex protein | 780 nm, 15 J/cm2, 0.75 W/cm2 | 6 sessions (Alternate days) | Improved the myelin density and morphological characteristics; The capillary density and ultrastructural characteristics were similar to the control group |
| Yang et al., 2016 [106] | Nerve injury | Sciatic nerve crush | Sprague–Dawley rats | M / Adult | Mesenchymal stem cells | 660 nm, 9 J/cm2 | 7 days | Provided greater functional recovery; Potentiated recovery in SFI, VA and AA; Increased electrophysiological function and expression of S100 immunoreactivity; Reduced the inflammatory cells |
| Dias et al., 2015 [107] | Nerve injury | Sciatic nerve crush | Wistar rats | M | Latex protein | 780 nm, 15 J/cm2, 0.75 W/cm2 | 6 sessions (Alternate days) | Improvement of the nerve characteristics including the morphometric and ultrastructural characteristics of nerve fibers |
| Muniz et al., 2015 [108] | Nerve injury | Sciatic nerve crush | Wistar rats | M | Natural latex protein | 780 nm, 15 J/cm2, 0.75 W/cm2 |
12 days (6/48 h) |
Improved muscle fiber atrophy; Increased light fiber area and reduced dark fiber area |
| de Souza et al., 2018 [109] | Nerve injury | Sciatic nerve crush | Swiss mice | M / Adult | Dexamethasone | 660 nm, 10 J/cm2 | 28 days | Improved nerve regeneration through the SSI and SFI assessments |
| Dias et al., 2019 [110] | Nerve injury | Sciatic nerve crush | Wistar rats | M / 2 months | Natural latex protein | 780 nm, 15 J/cm2, 0.75 W/cm2 | 6 sessions (Alternate days) | Improved nerve fiber regeneration; Reduced the number, density, diameter and organization of nerve fibers; Increased NGF, VEGF |
| de Souza et al., 2021 [111] | Nerve injury | Sciatic nerve crush | Swiss mice | M / 3 months | Simvastatin | 660 nm, 10 J/cm2 | 28 days | Sciatic functional index, thermal heat hyperalgesia, mechanical hyperalgesia, and thermographic were evaluated; The results showed that PBM alone was more effective compared to Simvastatin alone or combination |
| Souza et al., 2013 [112] | Nerve injury | Spinal cord injury | Wistar rats | M / 20—21 weeks | Monosialoganglioside | NM | 42 days | Combination therapy shows no superior functional, neurological or histological results |
| Janzadeh et al., 2017 [113] | Nerve injury | Spinal cord injury | Wistar rats | M / Adult | Chondroitinase ABC | 660 nm, 0.5 J/cm2, 0.819 W/cm2 | 14 days | Improved motor function recovery, myelination and number of axons; Decreased GSK3β, CSPG, and AQP4 expression |
| Pedram et al., 2018 [114] | Nerve injury | Spinal cord injury |
Fischer-344, Wistar rats |
M / 8 – 12 weeks | Meloxicam | 810 nm, 6 J/cm2, 200 mW/cm2 | 2 weeks |
Increased BBB test results; Histological findings revealed no significant difference between all study groups |
| Sarveazad et al., 2019 [115] | Nerve injury | Spinal cord injury | Wistar rats | M / Adult | Human adipose derived stem cells | 660 nm | 2 weeks | Improved the motor function, SCI-induced allodynia and hyperalgesia; Increased the GDNF, GABA receptors and Gad65 expression level; Reduced the expression of GSK3β, IL-6, AQP4 |
| Janzadeh et al., 2020 [116] | Nerve injury | Spinal cord injury | Wistar rats | M / Adult | Chondroitinase ABC | 660 nm, 22.8 J/cm2, 500 mW/cm2 | 2 weeks | Reduced allodynia and thermal hyperalgesia; Improved functional recovery; Did not reduce mechanical hyperalgesia; Decreased BDNF and IL-6; Increased Gad65 and GDNF; Reduced neuropathic pain; Improved movement |
| Chen et al., 2021 [117] | Nerve injury | Spinal cord injury | Sprague–Dawley rats | M / 12 weeks | Human umbilical cord mesenchymal stem cells | 630 nm, 100 mW/cm2 | 14 days | Improved neurofilament structure and arrangement; Promoted motor function and neuronal recovery; Increased the expression of NF‐200, glial fibrillary acidic protein in the damaged area and the BBB scores; Nissl bodies were more numerous and the nerve fibers were longer and thicker; Reduced lesions volume and secondary damage; Promoted functional recovery |
| Dong et al., 2015 [118] | Nerve injury | Traumatic brain injury | C57BL/6 mice | NM / 8 weeks | Lactate / Pyruvate | 810 nm, 36 J/cm2, 150 mW/cm2 | NM | Retained memory and learning activities of injured mice to a normal level; Low levels of glycolysis; Increased ATP; Reduced formation of ROS and apoptosis in neurons |
| Buchaim et al., 2016 [119] | Nerve injury | Facial nerve injury | Wistar rats | M / 60 days | Heterologous fibrin sealant | 830 nm, 6 J/cm2, 258.6 mW/cm2 |
5 weeks (3/week) |
Combination group presented the closest results to the control, in all nerve morphometry indexes (regeneration), except in the axon area |
| de Oliveira Rosso et al., 2017 [120] | Nerve injury | Facial nerve injury | Wistar rats | M / 80 days | Heterologous fibrin sealant | 830 nm, 6.2 J/cm2, 0.26 W/cm2 |
5 weeks (3/week) |
A significant difference in the fiber nerve area; The functional recovery of whisker movement; Accelerated morphological and functional nerve repair |
| Jameie et al., 2014 [121] | Pain |
Neuropathic pain (Chronic constriction injury model) |
Wistar rat | M / Adult | CoQ10 | 980 nm, 4 J/cm2, 0.248 W/cm2 | 2 weeks |
Cellular and molecular synergism on pain relief; Increased thermal and mechanical sense thresholds |
| Noma et al., 2020 [122] | Pain |
Neuropathic pain (Trigeminal nerve injury) |
Sprague–Dawley Wistar rat | M / 5–6 weeks | Oxytocin | 810 nm, 0.1 W | 3 days | The expanded area of cortical excitation caused by model was suppressed by combination therapy but not by each treatment alone; Combined application is effective in relieving the neuropathic pain |
| Martins et al., 2020 [123] | Pain | Orofacial pain | Wistar rats | M / 2 months | Vitamins B complex | 904 nm, 6 J/cm2 | 10 sessions | Maximal antiallodynic effect; Improved the nociceptive behavior; Down-regulated expression of GFAP, Iba-1, IL-1β, IL-6 and TNF-α; Increased IL-10 expression |
| de Freitas Dutra Júnior et al., 2022 [124] | Pain | Calcaneus tendon injury | Wistar rats | NM / 60 days | Heterologous fibrin biopolymer | 660 nm, 6 J/cm2, 1 W/cm2 |
3 weeks (1/week) |
Reduced the volume of the edema; Stimulate the repair process; Tenocyte proliferation, granulation tissue and collagen formation were observed in the PTCT area |
AA ankle angle, AQP4 aquaporin 4, ATP adenosine triphosphate, BAX Bcl-2 associated X protein, BBB Basso-Beattie-Bresnahan test, Bcl-2 B-cell lymphoma 2, BDNF brain-derived neurotrophic factor, CoQ10 Coenzyme Q10, CREB cAMP response element-binding, CSPG chondroitin sulfate proteoglycan, F Female, GABA Gamma-aminobutyric acid, Gad65 Glutamic acid decarboxylase65, GDNF glial-derived neurotrophic factor, GFAP glial fibrillary acid protein, GPx glutathione peroxidase, GSH glutathione, GSK3β glycogen synthase kinase-3β, HIP hippocampus, Iba-1 ionized calcium binding adaptor molecule 1, IL-10 Interleukin-10, IL-1β Interleukin-1β, IL-6 interleukin-6, iNOS inducible NO synthase, JNK c-Jun aminoterminal kinases, M Male, NF‐200 neurofilament 200, NF-kB nuclear factor-Kb, NGF nerve growth factor, NM not mentioned, NO nitric oxide, NRF1 nuclear respiratory factor 1, PFC prefrontal cortex, PGC1-α peroxisome proliferator-activated receptor gamma coactivator-1 alpha, PTCT partial transection of the calcaneus tendon, ROS reactive oxygen species, SFI Sciatic Functional Index, SIRT1 silent mating-type information regulation 2 homolog 1, SOD superoxide dismutase, SSI Sciatic Static Index, TAC total antioxidant capacity, TFAM mitochondrial transcription factor A, TNF-α tumor necrosis factor-alpha, tPA tissue plasminogen activator, TrkB tyrosine receptor kinase B, VA vertical activity of locomotion, VEGF vascular endothelium growth factor