Table 3.

Effects of experimental PBM on animals.

No	References/Year	Experimental Model	Type of Light/Devices	PBM Before/After Activity	The Fluence Expressed in J/cm2	Power Density mW/cm2	Parameters Analyzed	Effects	Results
[78]	Macedo, M.M.; Mafra, F.F.P.; Teixeira, C.B.; et al. Photobiomodulation therapy modulates muscle gene ex-pression and improves performance of rats subjected to a chronic resistance exercise protocol. Photobiomodul. Photomed. Laser Surg. 2020, 38, 12, 713–719. doi:10.1089/photob.2019.4792.	Male Wistar rats in vivo protocols. PBM were applied in direct contact with the skin without shaving on the gastrocnemius anatomical region, 50 s in each paw, 5 days on week for 4 weeks and 9 J per paw totaling 18 J of energy per day.	904 nm GaAs Pulsed 60 mW Number of diodes = 3.	The animals were irradiated before exercise on the hind legs.	6 J/cm2 Energy/point 3 J Total energy 18 J Time 50 s each side.	0.12 W/cm2	RNA ribosomal 18 s mTOR; myHC; AR; LDH	No statistical difference was observed for Gastrocnemius muscle mass. PBM increased expression of LDH enzyme and gene expression compared to nonirradiated animals.	PBMT did not increase gastrocnemius muscle mass, but improved performance in endurance training, increased expression of performance-related genes and the process of muscle protein synthesis.
[79]	Malta, E.S.; Ferraresi, C.; Monte, M.G.; et al. Effect of 12 weeks of endurance training combined with creatine supplement, photobiomodulation therapy, or both on performance and muscle damage in rats. Photobiomodul. Photomed. Laser Surg. 2020, 38, 12, 708–712. doi:10.1089/photob.2019.4793.	Twenty-five male Wistar rats weighing similar to 300 g were randomly distributed into five groups.	PBMT was delivered in six points with a laser device 808 nm, 100 mW, 30 s.	After	Energy per point of irradiation: 3 J; 75 J/cm2.	100 mW	Peak force and time of force decay during an electrical stimulation protocol CK levels.	PBMT with or without Cr supplement significantly improved performance than all the other groups.	PBMT alone or in conjunction with Cr supplement during a 12-week training program resulted in significantly better muscle performance and lower levels of CK.
[80]	Yamada, E.F.; Bobinski, F.; Martins, D.F.; et al. Photobiomodulation therapy in knee osteoarthritis reduces oxidative stress and inflammatory cytokines in rats. J. Biophotonics 2020, 13, 1, 201900204. doi:10.1002/jbio.201900204.	Knee osteoarthritis (OA) of the rat induced by monosodium iodoacetate (MIA).	GaAs (gallium-arsenide) 904 nm Pulsed + 9500 Hz.	After	Eight sessions of PBM 3 days/week, 6 or 18 J/cm2.	40 mW average radiant power; 70 W of peak radiant power; and 0.1309 cm2 spot area.	The inflammatory process, pain and cytokine levels (IL1-β, IL-6, IL-10, TNF-alfa), mechanical and cold hyperalgesia spontaneous pain.	18 J/cm2 dose of PBM reduced the pain and polymorpho-nuclear activity of neutrophils in the joint fluid, improved the parameters of oxidative stress in blood serum and spinal cord samples.	PBM improved antioxidant capacity, decreased the level of proinflammatory cytokines, reduced inflammation of the knee joint and pain.
[81]	Neves, L.M.S.; Gonçalves, E.C.D.; Cavalli, J.; et al. Photobiomodulation therapy improves acute inflammatory response in mice: the role of cannabinoid receptors/ATP-sensitive K+ channel/p38-MAPK signalling path-way. Mol. Neurobiol. 2018, 55, 5580–5593. https://doi.org/10.1007/s12035-017-0792-z.	Male Swiss mice were randomized.	660 nm; AlGaInP (aluminum/gallium/indium/phosphorus) Power: 30 mW, beam area 0.06 cm2, and CW output.	After	1, 20, 50, 100, 150, 200 J/cm2.	30 mW/cm2.	IL-6 and IL-10 catalepsy and motor activity Assessment Involvement of ATP-Sensitive K+ Channel and p38 MAP-kinase pathway Thermal nociceptive response test.	PBM (50 J/cm2, plantar irradiation) significantly inhibited carrageenan-induced paw oedema through modulation to both CB1 and CB2 cannabinoid receptors. PBMT significantly reduced the level of the pro-inflammatory cytokine IL-6 in both the paws and the spinal cord, as well as the low level of the anti-inflammatory cytokine IL-10 in the spinal cord after carrageenan injection.	PBM opens opportunity for non-pharmacological and non-psychotropic therapy during immune-mediated inflammatory diseases, including ankylosing spondylitis, type 1 diabetes, rheumatoid arthritis, and multiple sclerosis.
[82]	Dos Santos, L.S.; Saltorato, J.C.; Monte, M.G.; et al. PBMT and topical diclofenac as single and combined treatment on skeletal muscle injury in diabetic rats: Effects on biochemical and functional aspects. Lasers Med. Sci. 2019, 34, 2, 255–262. doi:10.1007/s10103-018-2580-z.	Randomly experimental model of muscle injury through controlled trauma in diabetic rats.	830 nm CW; 0.028 cm2 spot area. 3.57 W/cm2.		107.51 J/cm2 energy density; and 3 J (30 s) dose of energy per point.	100 mW/cm2.	Gene expression levels of COX-1 in the anterior tibial muscle. Levels of PGE2 in blood samples. Functional index.	PBMT was effective in reducing inflammatory markers (COX-2) and greatly improved the repair process of injured musculoskeletal tissue, at an energy density of 107.1 J/cm2 and total energy of 3 J.	PBMT, alone or in combination with diclofenac, decreased the concentration of inflammatory markers and improved the gait of diabetic rats in the acute phase of muscle injury.
[83]	Tomazoni, S.S.; Frigo, L.; dos Reis Ferreira, T.C.; et al. Effects of photobiomodulation therapy and topical non-steroidal anti-inflammatory drug on skeletal muscle injury induced by contusion in rats—Part 1: morphological and functional aspects. Lasers Med. Sci. 2017, 32, 9, 2111–2120. https://doi.org/10.1007/s10103-017-2346-z.	Ninety-six male Wistar rats were randomized and divided into experimental groups of six animals per group. The animals were submitted to the muscle contusion model produced on the anterior tibial muscle.	830 nm CW; spot area of 0.028 cm2, 100 mW.	PBMT was performed one hour after the induction of muscle injury by contusion.	Doses: 35.7; 107.1; 321.4 J/cm2 Irradiation time per site (s): 10, 30, 90, as follows: 1 J-35.7 J/cm2, 3 J-107.1 J/cm2, 9 J-321.4 J/cm2. 10, 30, and 90 s.	3.57 W/cm2	Morphological analysis—histology. Muscular work Muscle fatigue, tetanic and muscular contraction.	At 6 h, 12 h, and especially 24 h after injury, the three groups treated with PBMT (the best dose of 9 J in total 321.4 J/cm2) greatly improved the morphological aspects (organization of muscle fibers and cell nuclei) and inflammation compared to diclofenac group.	PBMT with 3 J (107.1 J/cm2), was the most valuable dose of the three used in the study and superior to local NSAID therapy to improve morphological and functional alterations due to muscle injury from contusion.
[84]	Tomazoni, S.S.; Frigo, L.; Dos Reis Ferreira, T.C.; et al. Effects of photobiomodulation therapy and topical non-steroidal anti-inflammatory drug on skeletal muscle injury induced by contusion in rats—Part 2: bio-chemical aspects. Lasers Med. Sci. 2017, 32, 8, 1879–1887. doi:10.1007/s10103-017-2299-2.	Ninety-six male Wistar rats were randomized. Muscle injury was induced by trauma to the anterior tibial muscle of rats.	830 nm CW; spot area of 0.028 cm2, 100 mW	PBMT was performed one hour after the induction of muscle injury by contusion.	Doses 35.7; 107.1; 321.4 J/cm2 Irradiation time per site (s) 10, 30, 90.	3.57 W/cm2	Gene expression of TNF- α and COX-2 (for 6, 12 and 24 h) in the anterior tibialis muscle ELISA for the detection of TNF-α IL-1β and IL-6 expressions and β-actin. PBMT activates the biostimulation process, which accelerates the resolution of acute inflammatory response and tissue regeneration.	PBMT 1 J (35.7 J/ cm2), 3 J (107.1 J/cm2), and 9 J (321.4 J/cm2) reduced levels of TNF-α, IL-1β, and IL-6 at all assessed times as compared to the injury and diclofenac groups.	PBMT with 3 J (107.1 J/cm2), was the most valuable dose of the three used in the study and superior to local NSAID therapy for improvement after muscle injuries from contusion. PBMT may be suggested as the best alternative for the treatment of muscle contusion given its role in the modulation of inflammation and consequently in tissue repair.
[85]	Silva, G.; Ferraresi, C.; de Almeida, R.T.; et al. Insulin resistance is improved in high-fat fed mice by photo-biomodulation therapy at 630 nm. J. Biophotonics 2020, 13, 3, e201960140. doi:10.1002/jbio.201960140.	Thirty-four 8-week-old male Swiss albino mice.	630 ± 20 nm CW.	Before and after	31.188 J/cm2 Energy delivered per site: 12 J. No. of irradiation sites: 5. Total irradiation time 200 s. Total energy delivered per day: 60 J.	779.53 mW/cm2	Histological analysis Protein analysis Blood glucose concentration Effect of low-fat diet (LFD) or high-fat diet (HFD). Adipocyte hypertrophy and inflammatory infiltrate.	PBMT improved glucose tolerance, insulin resistance and fasting hyperinsulinemia.	PBMT at 630 nm, CW, improved insulin resistance and glucose metabolism in HFD-fed mice.
[86]	De Brito Vieira, W.H.; Ferraresi, C.; Schwantes, M.L.B.; et al. Photobiomodulation increases mitochondrial citrate synthase activity in rats submitted to aerobic training. Lasers Med. Sci. 2018, 33, 4, 803–810. https://doi.org/10.1007/s10103-017-2424-2.	Fifty-four rats were allocated into four groups.	780 nm (GaAlAs). Beam area of 0.04 cm2.Energy per point of 0.15 J. Total energy of 1.2 J (per session for animal). Time of irradiation per point equal 10 s; CW; during 30 days of training.	After physical effort (days of training and effort tests).	Fluency of 3.8 J/cm2.	Irradiance of 37.5 mW/cm2.	LDH and CS activity LDH/CS ratios.	CS activity in the heart and soleus muscles in the exercise and PBM group was significantly higher, and LDH activity was lower (soleus muscle) than in the other groups.	PBM and treadmill aerobic training together participate in increasing the oxidative capacity especially of tissues with aerobic metabolism, such as in the soleus and heart muscles.
[87]	Frigero, M.; dos Santos, S.A.; Serra, A.J.; et al. Effect of photobiomodulation therapy on oxidative stress markers of gastrocnemius muscle of diabetic rats subjected to high-intensity exercise. Lasers Med. Sci. 2018, 33, 8, 1781–1790. https://doi.org/10.1007/s10103-018-2540-7.	Twenty-four male Wistar diabetic rats subjected to high-intensity exercise, were randomly allocated to groups of eight animals each; this study comprised 16 diabetic (with fatigue, and PBMT diabetic fatigue) and eight control rats.	808 nm 30 mW 0.028 cm2	Prior to each training session.	Total energy (Joule) = 24 142.4 J/cm2	1.071 mW/cm2	Blood lactate concentrations High-intensity exercise Volumes of oxygen (VO2) and carbon dioxide (VCO2). VO2ma xConcentrations of TBARS/MDA SOD, CAT, GPx activity GPx and SOD.	The PBMT diabetic fatigue group was irradiated before starting the exercises, with a dose of 4 J and 808 nm, and were subjected to running with speed and gradually slope to exhaustion. Analyzes of CAT, SOD and GPx activities were found to be significantly higher in the PBMT fatigue group than in the diabetic fatigue group.	PBM can reduce oxidative stress and may be an alternative treatment option to support fitness when subjects are unable to activate.
[88]	Da Silva Neto Trajano, L.A.; Trajano, E.T.L.; da Silva Sergio, L.P.; et al. Photobiomodulation effects on mRNA levels from genomic and chromosome stabilization genes in injured muscle. Lasers Med. Sci. 2018, 33, 7, 1513–1519. https://doi.org/10.1007/s10103-018-2510-0.	Cryoinjury was induced by two applications of a metal probe cooled in liquid nitrogen directly on the tibialis anterior muscle in rat. Wistar male rats were randomly divided into six groups.	904 nm GaAs	after injury.	3 J/cm2 3 J/cm2 Four irradiation procedures (3 J/cm2 per irradiation, totaling 12 J/cm2.	25 mW 75 mW	Total mRNA extraction Complementary DNA (cDNA) synthesis Telomeric repeat binding factors (TRF1 and TRF2), ATM serine/threonine kinase. Tumor protein p53 (P53), Glyceraldehyde-3- phosphate dehydrogenase (GAPDH) primers.	PBM (904 nm, 3 J/cm2 per irradiation, 25 and 75 mW, 4 irradiations) significantly reduced TRF1 mRNA levels in injured muscle exposed to laser, compared to the injury group.	PBM at 25 and 75 mW reduced the mRNA levels from ATM and p53, as well as mRNA levels from TRF1 and TRF2 in injured skeletal muscle. In conclusion, PBM altered mRNA relative levels from the genes related to genomic and telomere stabilization in injured skeletal muscle.
[89]	Ferraresi, C.; de Sousa, M.V.; Huang, Y.Y.; et al. Time response of increases in ATP and muscle resistance to fatigue after low-level laser (light) therapy (LLLT) in mice. Lasers Med. Sci. 2015, 30, 1259–1267. doi:10.1007/s10103-015-1723-8.	Fifty male Balb/c mice were randomly allocated into two equal groups: LEDT-ATP and LEDT-fatigue. Both groups were subdivided into five equal subgroups: LEDT-sham, LEDT-5 min, LEDT-3 h, LEDT-6 h, and LEDT-24 h.	Forty LEDs: 20 red (630 ± 10 nm, 25 mW); 20 infrared (850 ± 20 nm, 50 mW). CW.	LEDT applied to legs, gluteus, and lower back muscles, as follows: LEDT-sham; LEDT-5 min before; LEDT-3 h before; LEDT-6 h before; LEDT-24 h before.	Optical output each LED: 50 mW (IR) and 25 mW (RED). Optical output (cluster): 1000 mW (IR) and 500 mW (RED). Treatment time: 90 s Energy density: 7.2 J/cm2.	Power density: 80 mW/cm2. Distance from mice or power meter: 45 mm.	Fatigue test was performed by mice repeatedly climbing an inclined ladder bearing a load of 150% of body weight until exhaustion.	Time response for LEDT-mediated increase in adenosine triphosphate (ATP) in the soleus and gastrocnemius muscles. LEDT effects on the resistance of muscles to fatigue during intense exercise.	LEDT-6 h had the highest muscle ATP content and the highest number of repetitions in the fatigue test, compared to all subgroups. Conclusion: LEDT increased ATP content in muscles and fatigue resistance in mice with a peak at 6 h.
[90]	Ferraresi, C.; Parizotto, N.A.; Pires de Sousa, M.V.; et al. Light-emitting diode therapy in exercise-trained mice increases muscle performance, cytochrome c oxidase activity, ATP and cell proliferation [J. Biophotonics 8, No. 9, 740–754 (2015)]. J. Biophotonics 2016, 9, 976. doi:10.1002/jbio.201680087.	Twenty-two male Balb/c mice were randomly divided into 5 groups: LEDT-Sham group (5); LEDT-Before (5); LEDT-Before-After (5); LEDT-After (5); Control (2): no LEDT, no exercise. LEDT over both legs, gluteus and lower-back muscles at a distance of 45 mm (without contact).	Forty LEDs (20 red –630 ± 10 nm; 20 infrared −850 ± 20 nm) with diameter of 76 mm. CW.	Complex protocol depending on group: - Sham; - Before; - Before and after; - After; control no LEDT, no exercise.	Optical output each LED: 50 mW (IR) and 25 mW (RED) optical output (cluster): 1000 mW (IR) and 500 mW (RED). Treatment time: 90 s. Energy density applied (at skin surface): 7.2 J/cm2.	LED cluster size: 45 cm2. Power density (at skin surface): 80 mW/cm2. Application mode: without contact. Distance from mice or power meter: 45 mm.	Three repetitions maximum load (3 RM) After 24 h from initial 3 RM baseline: 6 training sessions on alternate days (every 48 h), as follows: 5 sets of 10 repetitions (climbs) on the ladder with a rest period of 2 min between each set. - Distance climbed (in cm); - number of repetitions/set; - time/exercise. From these data were calculated: - muscle work and - muscle power in each training session.	Evaluation of the muscle performance in each group; muscular ATP; muscular glycogen; Oxidative stress markers; Immunofluorescence analyses Cytochrome c oxidase subunit IV.	Clear improvement in muscle performance, energy metabolism, oxidative stress defense and repair/proliferation with different regimens of LEDT applied to muscles in conjunction with a training regimen. Six bi-daily training sessions LEDT-After and LEDT-Before-After regimens more than doubled muscle performance and increased ATP more than tenfold.
[91]	Tomazoni, S.S.; Leal-Junior, E.C.; Frigo, L.; et al. Isolated and combined effects of photobiomodulation therapy, topical nonsteroidal anti-inflammatory drugs, and physical activity in the treatment of osteoarthritis induced by papain. J. Biomed. Opt. 2016, 21, 10, 108001. doi:10.1117/1.JBO.21.10.108001.	Fifty-four Wistar rats were randomly divided into experimental groups: NSAID, physical activity, and PBMT applied alone and/or in combination between groups.	830 nm CW, spot area of 0.028 cm2, 100 mW.	Twenty-one days after the last injection of papain to induce OA, PBM was applied 3 times a week (every other day) for 8 consecutive weeks for a total of 24 therapy sessions.	214; 2 J∕cm2, 6 J per point, 60 s per point, 1 point on the OA join, in direct contact with the skin.	35.71 W/cm2.	Histologic characterization of the knee joint. The total amount of cells in the articular cavity. MPO; HPRT; MMPs activity. Gene Expression of MMP-3 and MMP-13 by RT-PCR.	PBMT was the most effective for improving the parameters investigated, had no negative side effects or restrictions in musculoskeletal disorders.	PBMT was the best alternative among the therapies tested in this study because it has improved a lot of morphological changes and enzymes that were involved in joint damage.
[92]	Yang, L.; Dong, Y.; Wu, C.; et al. Photobiomodulation preconditioning prevents cognitive impairment in a neonatal rat model of hypoxia-ischemia. J. Biophotonics 2019, 12, 6, e201800359. https://doi.org/10.1002/jbio.201800359.	Ten-day-old neonatal Sprague-Dawley rats.	808 nm, CW.	PBM preconditioning.	12 J/cm2.	100 mW/cm2.	ATP contents in total proteins. Tests at P28 and P29 were conducted to test the recognition memory. The shrinkage volume and neuronal density in the hippocampal CA1 region HI-induced changes in mitochondrial fragmentation in hippocampal CA1 region on P16. Content of cytochrome c in mitochondria and cytosol, the activities of caspase-9 and caspase-3, and apoptosis after HI insults.	PBM can turn off the release of cytochrome C from mitochondria to cytoplasm followed by arresting mitochondria-mediated apoptotic pathway and neuronal apoptosis.	Authors concluded that PBM pre-treatment could suppress mitochondria-mediated apoptotic pathway and neuronal apoptosis by the preservation of mitochondria in an HI model. PBM to human infants who have already suffered an HI insult could improve the prognosis of this condition.
[93]	De Oliveira, H.A.; Antonio, E.L.; Silva, F.A.; et al. Protective effects of photobiomodulation against resistance exercise-induced muscle damage and inflammation in rats. J. Sports Sci. 2018, 36, 20, 2349–2357. doi:10.1080/02640414.2018.1457419.	Female Wistar rats were randomized.	830 nm spot area of 0.028 cm2, 100 mW.	Prior to (upper panel) and post-exercise	71.4 J/cm2 142.8 J/cm2 285.6 J/cm2 Energy per point (J): 2, 4, 8.	3.57 W/cm2	The blood levels of lactate, CK, and LDH Gene expression and skeletal muscle inflammation makers: TNF-α, IL-6, IL1-β, IL-10. Skeletal muscle macrophage infiltration: CD68, CINC-1, MCP-1. Morphological analysis—histology immunohistochemical assays. Familiarization and dynamic resistance exercise.	PBM reduced muscles damage induced by resistance exercise and decreased the CK and LDH levels at 4 J dose. PBM after exercise decreased muscle levels of IL-6, IL-1β, CINC-1, MCP-1 and IL-10 more than those in the control group at 24 h post-exercises. Decrease in CINC-1 may suggest a reduction in muscle oxidation due to growth of antioxidant activity.	PBM administered before and after exercise at a dose of 4 J reduces muscle destruction and inflammation. PBM could protect athletes from muscle injuries during exercise and accelerates repairs when they occur.