Efficacy of Acute and Long-Term Photobiomodulation Therapy on Fatigue and Muscle Performance in Different Animal Models: a Systematic Review

Vassão, Patricia Gabrielli; Balão, Ana Beatriz; Campos, Raquel Munhoz da Silveira; Sales, Abdias Fernando Simon; Parisi, Julia Risso; Andrade, Ana Laura Martins de; Tucci, Helga Tatiana; Garcia, Livia Assis; Renno, Ana Claudia Muniz

doi:10.1590/1678-4324-2024220678

Patricia Gabrielli Vassão ^**Correspondence: patriciavassao@gmail.com; Tel: +551332290204 (P.G.V.).

Universidade Federal de São Paulo, Departamento de Biociência, Santos, SP, Brasil

https://orcid.org/0000-0001-8728-1842

Ana Beatriz Balão

Universidade Federal de São Paulo, Departamento de Biociência, Santos, SP, Brasil

https://orcid.org/0000-0002-8906-5390

Raquel Munhoz da Silveira Campos

Universidade Federal de São Paulo, Departamento de Biociência, Santos, SP, Brasil

https://orcid.org/0000-0001-6132-4349

Abdias Fernando Simon Sales

Universidade Federal de São Paulo, Departamento de Biociência, Santos, SP, Brasil

https://orcid.org/0000-0002-8778-6346

Julia Risso Parisi

Universidade Metropolitana de Santos, Santos, SP, Brasil

https://orcid.org/0000-0002-4325-0638

Ana Laura Martins de Andrade

Universidade Brasil, Programa da Pós Graduação em Engenharia Biomédica, São Paulo, SP, Brasil

https://orcid.org/0000-0003-1137-7180

Helga Tatiana Tucci

Universidade Federal de São Paulo, Departamento de Ciências do Movimento Humano, Santos, SP, Brasil

in memoriam

https://orcid.org/0000-0003-0628-4086

Livia Assis Garcia

Universidade Federal de São Paulo, Departamento de Biociência, Santos, SP, Brasil

Universidade Metropolitana de Santos, Santos, SP, Brasil

https://orcid.org/0000-0002-8343-3375

Ana Claudia Muniz Renno

Universidade Federal de São Paulo, Departamento de Biociência, Santos, SP, Brasil

https://orcid.org/0000-0002-1927-5077

*Correspondence: patriciavassao@gmail.com; Tel: +551332290204 (P.G.V.).

Editor-in-Chief:

Paulo Vitor Farago

Associate Editor:

Paulo Vitor Farago

in memoriam

Conflicts of Interest:

The authors declare no conflict of interest.

Authors	Sample size	Species	Animal sex	Age	Body mass (g)	Analysis
dos Santos et al. [¹⁴14 Dos Santos SS, de Oliveira HA, Antonio EL, Teixeira ILA, Mansano BSDM, Silva FA, et al. Low-level laser therapy prevents muscle oxidative stress in rats subjected to high-intensity resistance exercise in a dose-dependent manner. Lasers Med Sci. 2020;35(8):1689-94.]	36	Wistar rats	Female	12 weeks	200 - 250	physical performance, Western blot (protein concentration), lipid and protein peroxidation and enzymatic activity (catalase and superoxide dismutase)
de Oliveira et al. [¹³13 de Oliveira HA, Antonio EL, Silva FA, de Carvalho PTC, Feliciano R, Yoshizaki A, et al. Protective effects of photobiomodulation against resistance exercise-induced muscle damage and inflammation in rats. J Sports Sci. 2018;36(20):2349-57.]	69	Wistar rats	Female	12 weeks	200 - 250	lactate, CK and LDH levels, macrophage infiltration, gene expression of TNF-α, IL-6, IL1-β, IL-10, CINC-1 and MCP-1; and exercise performance (climbing speed).
Albuquerque-Pontes et al. [²⁰20 Albuquerque-Pontes GM, Casalechi HL, Tomazoni SS, Serra AJ, Ferreira CSB, Brito RBO, et al. Photobiomodulation therapy protects skeletal muscle and improves muscular function of mdx mice in a dose-dependent manner through modulation of dystrophin. Lasers Med Sci. 2018; 33(4):755-64.]	25	wild type mice mdx mice	─	6 weeks	─	muscle morphology, exercise performance (climbing stairs), Western blot (protein concentration), and RT-PCR (expression of dystrophin)
de Brito Vieira et al. [¹⁵15 de Brito Vieira WH, Ferraresi C, Schwantes MLB, de Andrade Perez SE, Baldissera V, Cerqueira MS, et al. Photobiomodulation increases mitochondrial citrate synthase activity in rats submitted to aerobic training. Lasers Med Sci. 2018;33(4):803-10.]	54	Wistar rats	Male	30 days	112 ± 4.7	exercise performance (running speed), CS and LDH activities
Assis et al. [¹²12 Assis L, Yamashita F, Magri AM, Fernandes KR, Yamauchi L, Renno ACM. Effect of low-level laser therapy (808 nm) on skeletal muscle after endurance exercise training in rats. Braz J Phys Ther. 2015;19(6):457-65.]	24	Wistar rats	Male	6 weeks	± 200	exercise performance (running speed), lactate concentration, morphometric analysis, muscle fiber density and myogenin expression
Perini et al. [¹⁶16 Perini JL, Hentschke VS, Sonza A, Dal Lago P. Long-term low-level laser therapy promotes an increase in maximal oxygen uptake and exercise performance in a dose-dependent manner in Wistar rats. Lasers Med Sci. 2016;31(2):241-8.]	30	Wistar rats	Male	~90 days	270 - 320	exercise performance (metabolic treadmill with maximal oxygen and carbon dioxide production)
Silva et al. [²¹21 Silva AA, Leal-Junior EC, D'Avila Kde A, Serra AJ, Albertini R, França CM, et al. Pre-exercise low-level laser therapy improves performance and levels of oxidative stress markers in mdx mice subjected to muscle fatigue by high-intensity exercise. Lasers Med Sci. 2015;30(6):1719-27.]	28	wild type (C57BL/10ScSn) (n=7) and C57BL/10ScSn-Dmdmdx/J (n=21)	─	4 weeks	─	CK, superoxide dismutase, carbonyl protein and skeletal muscle morphology
Paolillo et al. [¹⁷17 Paolillo FR, Arena R, Dutra DB, de Cassia Marqueti Durigan R, de Araujo HS, de Souza HC, et al. Low-level laser therapy associated with high intensity resistance training on cardiac autonomic control of heart rate and skeletal muscle remodeling in wistar rats. Lasers Surg Med. 2014;46(10):796-803.]	40	Wistar rats	male	2-4 months	250 - 300	load peak, body mass, lactate, matrix metalloproteinase gelatinase A gene expression and heart rate variability
Patrocinio et al. [¹⁸18 Patrocinio T, Sardim AC, Assis L, Fernandes KR, Rodrigues N, Renno AC. Effect of low-level laser therapy (808 nm) in skeletal muscle after resistance exercise training in rats. Photomed Laser Surg. 2013;31(10):492-8.]	30	Wistar rats	male	8 weeks	300 - 350	body mass, maximal load, lactate, glycogen and muscle fiber morphometry
de Almeida et al. [¹⁹19 De Almeida P, Lopes-Martins RÁ, Tomazoni SS, Silva JA Jr, de Carvalho Pde T, Bjordal JM, et al. Low-level laser therapy improves skeletal muscle performance, decreases skeletal muscle damage and modulates mRNA expression of COX-1 and COX-2 in a dose-dependent manner. Photochem Photobiol. 2011;87(5):1159-63.]	30	Wistar rats	male	─	150 - 200	COX-1 and COX-2, CK and total work performed

Authors	Groups	Application area	PBMT application	Intervention
dos Santos et al. [¹⁴14 Dos Santos SS, de Oliveira HA, Antonio EL, Teixeira ILA, Mansano BSDM, Silva FA, et al. Low-level laser therapy prevents muscle oxidative stress in rats subjected to high-intensity resistance exercise in a dose-dependent manner. Lasers Med Sci. 2020;35(8):1689-94.]	Control: not submitted to RE or LLLT; RNI: submitted to a RE; RE+LLLT (4J); RE+LLLT (8J); RE+LLLT (12J)	Skin on both legs with a slight overpressure to central, proximal, and distal sites on gastrocnemius muscle	Acute	PBMT applied prior to a high-intensity resistance exercise session
de Oliveira et al. [¹³13 de Oliveira HA, Antonio EL, Silva FA, de Carvalho PTC, Feliciano R, Yoshizaki A, et al. Protective effects of photobiomodulation against resistance exercise-induced muscle damage and inflammation in rats. J Sports Sci. 2018;36(20):2349-57.]	Prior Exercise LLLT application: Control: n= 12; 2J irradiation: n= 12; 4J irradiation: n= 12; 8J irradiation: n= 13 Post Exercise LLLT application: Control: n= 10; 4J irradiation: n= 10	3 points on the hind legs	Acute	PBMT applied prior or post resistance exercise intervention
Albuquerque-Pontes et al. [²⁰20 Albuquerque-Pontes GM, Casalechi HL, Tomazoni SS, Serra AJ, Ferreira CSB, Brito RBO, et al. Photobiomodulation therapy protects skeletal muscle and improves muscular function of mdx mice in a dose-dependent manner through modulation of dystrophin. Lasers Med Sci. 2018; 33(4):755-64.]	Wild type-WT (C57BL/10ScSn) Untreated: n=5; Placebo-control group: DMD^mdx mice: n=5; 1 J group-DMD^mdx mice: n= 5; 3J group-DMD^mdx mice: n= 5; 10J group-DMD^mdx mice: n= 5	Tibialis anterior muscle (bilaterally)	Long-term	PBMT was applied 3 times a week on non-consecutive days (Monday, Wednesday, and Friday) for 14 weeks
de Brito Vieira et al. [¹⁵15 de Brito Vieira WH, Ferraresi C, Schwantes MLB, de Andrade Perez SE, Baldissera V, Cerqueira MS, et al. Photobiomodulation increases mitochondrial citrate synthase activity in rats submitted to aerobic training. Lasers Med Sci. 2018;33(4):803-10.]	RCG n= 10; RLG n= 9; ECG n= 16; ELG n= 19	Quadriceps femoris, tibialis anterior, soleus and gluteus maximus muscles of both hind limbs	Long-term	PBMT was applied immediately after aerobic exercise intervention and effort test. The exercise protocol was realized for 5 weeks (from Sunday to Thursday)
Assis et al. [¹²12 Assis L, Yamashita F, Magri AM, Fernandes KR, Yamauchi L, Renno ACM. Effect of low-level laser therapy (808 nm) on skeletal muscle after endurance exercise training in rats. Braz J Phys Ther. 2015;19(6):457-65.]	CG n= 8; TG n= 8; TLG n= 8	Middle region of quadriceps, gluteus maximus, tibialis anterior and gastrocnemius muscles in both legs	Long-term	PBMT applied after endurance training for 8 weeks
Perini et al. [¹⁶16 Perini JL, Hentschke VS, Sonza A, Dal Lago P. Long-term low-level laser therapy promotes an increase in maximal oxygen uptake and exercise performance in a dose-dependent manner in Wistar rats. Lasers Med Sci. 2016;31(2):241-8.]	P-LLLT n= 10; 8.7 J/cm²-LLLT n= 10; 61.2 J/cm²-LLLT n= 10	Biceps femoris, gluteus, gastrocnemius, iliopsoas, adductor longus (bilaterally)	Long-term	The maximal exercise test was realized on a metabolic treadmill (adaptation, before PBMT and after PBMT). PBMT was applied for 10 days
Silva et al. [²¹21 Silva AA, Leal-Junior EC, D'Avila Kde A, Serra AJ, Albertini R, França CM, et al. Pre-exercise low-level laser therapy improves performance and levels of oxidative stress markers in mdx mice subjected to muscle fatigue by high-intensity exercise. Lasers Med Sci. 2015;30(6):1719-27.]	WT group; mdx control group; mdx fatigue LLLT group; mdx fatigue group	On the foreleg in the posterior region of gastrocnemius muscle	Long-term	PMBT was applied during three consecutive days. A forced exercise test on a treadmill was applied in last day of PMBT protocol.
Paolillo et al. [¹⁷17 Paolillo FR, Arena R, Dutra DB, de Cassia Marqueti Durigan R, de Araujo HS, de Souza HC, et al. Low-level laser therapy associated with high intensity resistance training on cardiac autonomic control of heart rate and skeletal muscle remodeling in wistar rats. Lasers Surg Med. 2014;46(10):796-803.]	CG n= 10; HIT n= 10; LLLT n= 10; HIT plus LLLT n= 10	Center of both right and left tibialis anterior muscle	Long-term	PBMT was applied after the high intensity resistance training. It was performed for 24 exercise sessions, three times per week for 8 weeks.
Patrocinio et al. [¹⁸18 Patrocinio T, Sardim AC, Assis L, Fernandes KR, Rodrigues N, Renno AC. Effect of low-level laser therapy (808 nm) in skeletal muscle after resistance exercise training in rats. Photomed Laser Surg. 2013;31(10):492-8.]	CG: n= 10; TG: n= 10; TGL: n= 10	Middle region of tibialis anterior belly of both legs	Long-term	PMBT was applied after the resistance training, performed three times per week, for 15 sessions.
de Almeida et al. [¹⁹19 De Almeida P, Lopes-Martins RÁ, Tomazoni SS, Silva JA Jr, de Carvalho Pde T, Bjordal JM, et al. Low-level laser therapy improves skeletal muscle performance, decreases skeletal muscle damage and modulates mRNA expression of COX-1 and COX-2 in a dose-dependent manner. Photochem Photobiol. 2011;87(5):1159-63.]	CG: n= 6; LLLT 0.1J: n= 6; LLLT 0.3J: n= 6; LLLT 1.0J: n= 6; LLLT 3.0J: n= 6	Central part of dissected tibial muscle belly	Acute	PBMT was applied before the electrical stimulation protocol to induce tetanic contractions

Authors	Light	Treatment time per point or site (s)	Wavelength (nm)	Power Output (mW)	Energy density per diode (J/cm2)	Energy per site (J)	Power density Per diode (W/cm²)	Spot size (cm2)	Number of treated points or sites	Total sessions
Dos Santos et al., [¹⁴14 Dos Santos SS, de Oliveira HA, Antonio EL, Teixeira ILA, Mansano BSDM, Silva FA, et al. Low-level laser therapy prevents muscle oxidative stress in rats subjected to high-intensity resistance exercise in a dose-dependent manner. Lasers Med Sci. 2020;35(8):1689-94.]	LLLT	40 80 120	830	100	142.8, 285.6 or 428.4	4 8 12	3.57	0.028	6	1
De Oliveira et al., [¹³13 de Oliveira HA, Antonio EL, Silva FA, de Carvalho PTC, Feliciano R, Yoshizaki A, et al. Protective effects of photobiomodulation against resistance exercise-induced muscle damage and inflammation in rats. J Sports Sci. 2018;36(20):2349-57.]	LLLT	20 40 80	830	100	71.4, 142.8 or 285,6	2 4 8	3.57	0.028	6	1
Albuquerque -Pontes el al., [²⁰20 Albuquerque-Pontes GM, Casalechi HL, Tomazoni SS, Serra AJ, Ferreira CSB, Brito RBO, et al. Photobiomodulation therapy protects skeletal muscle and improves muscular function of mdx mice in a dose-dependent manner through modulation of dystrophin. Lasers Med Sci. 2018; 33(4):755-64.]	LLLT LEDT (4 red LEDT and 4 infrared LEDT)	8 23 77	LLLT: 905 Red LEDT: 640 Infrared LEDT: 875	LLLT: 0.625 Red LEDT: 15 Infrared LEDT: 17.5	5.07, 15.23, or 50.76	1.0, 3.0, or 10.0	0.66307	0.197	2	42
De Brito Vieira et al., [¹⁵15 de Brito Vieira WH, Ferraresi C, Schwantes MLB, de Andrade Perez SE, Baldissera V, Cerqueira MS, et al. Photobiomodulation increases mitochondrial citrate synthase activity in rats submitted to aerobic training. Lasers Med Sci. 2018;33(4):803-10.]	LLLT	10	780	15	3.8	0.15	0.0375	0,04	8	26
Assis et al., [¹²12 Assis L, Yamashita F, Magri AM, Fernandes KR, Yamauchi L, Renno ACM. Effect of low-level laser therapy (808 nm) on skeletal muscle after endurance exercise training in rats. Braz J Phys Ther. 2015;19(6):457-65.]	LLLT	47	808	30	180	1.4	3.8	0.00785	8	40
Perrini et al. (2015) [¹⁶16 Perini JL, Hentschke VS, Sonza A, Dal Lago P. Long-term low-level laser therapy promotes an increase in maximal oxygen uptake and exercise performance in a dose-dependent manner in Wistar rats. Lasers Med Sci. 2016;31(2):241-8.]	LLLT	1 or 7.3	850	300	8.7 or 61.2	0.315 or 2.205	8.33	0.012	12	10
Silva et al., [²¹21 Silva AA, Leal-Junior EC, D'Avila Kde A, Serra AJ, Albertini R, França CM, et al. Pre-exercise low-level laser therapy improves performance and levels of oxidative stress markers in mdx mice subjected to muscle fatigue by high-intensity exercise. Lasers Med Sci. 2015;30(6):1719-27.]	LLLT	100	808	30	107	3	1071	0.028	1	3
Paollilo et al., [¹⁷17 Paolillo FR, Arena R, Dutra DB, de Cassia Marqueti Durigan R, de Araujo HS, de Souza HC, et al. Low-level laser therapy associated with high intensity resistance training on cardiac autonomic control of heart rate and skeletal muscle remodeling in wistar rats. Lasers Surg Med. 2014;46(10):796-803.]	LLLT	10	780	15	3.8	0.15	0.0375	0.04	2	24
Patrocinio et al., [¹⁸18 Patrocinio T, Sardim AC, Assis L, Fernandes KR, Rodrigues N, Renno AC. Effect of low-level laser therapy (808 nm) in skeletal muscle after resistance exercise training in rats. Photomed Laser Surg. 2013;31(10):492-8.]	LLLT	33	808	100	120	3.3	3.57	0.028	2	15
De Almeida et al., [¹⁹19 De Almeida P, Lopes-Martins RÁ, Tomazoni SS, Silva JA Jr, de Carvalho Pde T, Bjordal JM, et al. Low-level laser therapy improves skeletal muscle performance, decreases skeletal muscle damage and modulates mRNA expression of COX-1 and COX-2 in a dose-dependent manner. Photochem Photobiol. 2011;87(5):1159-63.]	LLLT	7, 20, 67 or 200	904	15	0.525, 1.5, 5.025 or 15	0.105, 0.300, 1 or 3	0.075	0.2	1	1

	Treatment time per point or site (s)	Wavelength (nm)	Power output (mW)	Energy density per diode (J/cm²)	Energy per site (J)	Energy delivered per treatment/session (J)	Total energy delivered per experiment / whole protocol	Power density per diode (W/cm²)	Spot size (cm²)	Number of treated points or sites	Total Sessions
Minimum	1	640	0.625	0.525	0.105	0.105	0.105	0.0375	0.00785	1	1
Maximum	200	905	300	428.4	12	72	840	8.33	0.2	12	42
Mean	49.5	818.16	61.51	96.71	3.34	14.63	105.18	2.4724	0.060885	4.41	10
Median	36.5	819	23.75	55.98	2.60	6.3	27.6	2.3205	0.028	6	1

	PBMT on fatigue levels- in experimental model
Outcome	Limitations	Inconsistency	Indirectness	Imprecision	Publications Bias	Trials	Intervention (n)	Comparison (n)	Significant difference or statistics	GRADE level of evidence
Intervention: PBMT x control/sham
Variable: histological analysis
						Albuquerque-Pontes et al., [ ²⁰20 Albuquerque-Pontes GM, Casalechi HL, Tomazoni SS, Serra AJ, Ferreira CSB, Brito RBO, et al. Photobiomodulation therapy protects skeletal muscle and improves muscular function of mdx mice in a dose-dependent manner through modulation of dystrophin. Lasers Med Sci. 2018; 33(4):755-64. ]	5	5	Yes
						Assis et al., [ ¹²12 Assis L, Yamashita F, Magri AM, Fernandes KR, Yamauchi L, Renno ACM. Effect of low-level laser therapy (808 nm) on skeletal muscle after endurance exercise training in rats. Braz J Phys Ther. 2015;19(6):457-65. ]	8	8	Yes
						Silva et al., [ ²¹21 Silva AA, Leal-Junior EC, D'Avila Kde A, Serra AJ, Albertini R, França CM, et al. Pre-exercise low-level laser therapy improves performance and levels of oxidative stress markers in mdx mice subjected to muscle fatigue by high-intensity exercise. Lasers Med Sci. 2015;30(6):1719-27. ]	5	5	Yes
						Patrocinio et al., [ ¹⁸18 Patrocinio T, Sardim AC, Assis L, Fernandes KR, Rodrigues N, Renno AC. Effect of low-level laser therapy (808 nm) in skeletal muscle after resistance exercise training in rats. Photomed Laser Surg. 2013;31(10):492-8. ]	10	10	Yes
	Serious	No	No	No	Undetected					Moderate **
Variable: Blood level of lactate
						de Oliveira et al., [ ¹³13 de Oliveira HA, Antonio EL, Silva FA, de Carvalho PTC, Feliciano R, Yoshizaki A, et al. Protective effects of photobiomodulation against resistance exercise-induced muscle damage and inflammation in rats. J Sports Sci. 2018;36(20):2349-57. ]	12	12	Yes
						de Brito Vieira et al., [ ¹⁵15 de Brito Vieira WH, Ferraresi C, Schwantes MLB, de Andrade Perez SE, Baldissera V, Cerqueira MS, et al. Photobiomodulation increases mitochondrial citrate synthase activity in rats submitted to aerobic training. Lasers Med Sci. 2018;33(4):803-10. ]	19	10	Yes
						Assis et al., [ ¹²12 Assis L, Yamashita F, Magri AM, Fernandes KR, Yamauchi L, Renno ACM. Effect of low-level laser therapy (808 nm) on skeletal muscle after endurance exercise training in rats. Braz J Phys Ther. 2015;19(6):457-65. ]	8	8	Yes
						Paolillo et al., [ ¹⁷17 Paolillo FR, Arena R, Dutra DB, de Cassia Marqueti Durigan R, de Araujo HS, de Souza HC, et al. Low-level laser therapy associated with high intensity resistance training on cardiac autonomic control of heart rate and skeletal muscle remodeling in wistar rats. Lasers Surg Med. 2014;46(10):796-803. ]	10	10	Yes
						Patrocinio et al., [ ¹⁸18 Patrocinio T, Sardim AC, Assis L, Fernandes KR, Rodrigues N, Renno AC. Effect of low-level laser therapy (808 nm) in skeletal muscle after resistance exercise training in rats. Photomed Laser Surg. 2013;31(10):492-8. ]	10	10	Yes
	No	No	No	Serious	Undetected					Moderate **

[1] *Correspondence: patriciavassao@gmail.com; Tel: +551332290204 (P.G.V.).

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Efficacy of Acute and Long-Term Photobiomodulation Therapy on Fatigue and Muscle Performance in Different Animal Models: a Systematic Review

Abstract

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