Anti-hyperalgesic Effects of Photobiomodulation Therapy (904 nm) on Streptozotocin-induced Diabetic Neuropathy Imply MAPK Pathway and Calcium Dynamics Modulation

Overview

Journal Sci Rep

Specialty Science

Date 2022 Oct 6

PMID 36202956

Authors

Willians Fernando Vieira

Kaue Franco Malange

Silviane Fernandes de Magalhaes

Julia Borges Paes Lemes

Gilson Goncalves Dos Santos

Catarine Massucato Nishijima

Alexandre Leite Rodrigues de Oliveira

Maria Alice da Cruz-Hofling

Claudia Herrera Tambeli

Carlos Amilcar Parada

Affiliations

Soon will be listed here.

Abstract

Several recent studies have established the efficacy of photobiomodulation therapy (PBMT) in painful clinical conditions. Diabetic neuropathy (DN) can be related to activating mitogen-activated protein kinases (MAPK), such as p38, in the peripheral nerve. MAPK pathway is activated in response to extracellular stimuli, including interleukins TNF-α and IL-1β. We verified the pain relief potential of PBMT in streptozotocin (STZ)-induced diabetic neuropathic rats and its influence on the MAPK pathway regulation and calcium (Ca) dynamics. We then observed that PBMT applied to the L4-L5 dorsal root ganglion (DRG) region reduced the intensity of hyperalgesia, decreased TNF-α and IL-1β levels, and p38-MAPK mRNA expression in DRG of diabetic neuropathic rats. DN induced the activation of phosphorylated p38 (p-38) MAPK co-localized with TRPV1 neurons; PBMT partially prevented p-38 activation. DN was related to an increase of p38-MAPK expression due to proinflammatory interleukins, and the PBMT (904 nm) treatment counteracted this condition. Also, the sensitization of DRG neurons by the hyperglycemic condition demonstrated during the Ca dynamics was reduced by PBMT, contributing to its anti-hyperalgesic effects.

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References

Aleksic V, Aoki A, Iwasaki K, Takasaki A, Wang C, Abiko Y . Low-level Er:YAG laser irradiation enhances osteoblast proliferation through activation of MAPK/ERK. Lasers Med Sci. 2010; 25(4):559-69. DOI: 10.1007/s10103-010-0761-5. View

Thornalley P . Glycation in diabetic neuropathy: characteristics, consequences, causes, and therapeutic options. Int Rev Neurobiol. 2002; 50:37-57. DOI: 10.1016/s0074-7742(02)50072-6. View

Chung H, Dai T, Sharma S, Huang Y, Carroll J, Hamblin M . The nuts and bolts of low-level laser (light) therapy. Ann Biomed Eng. 2011; 40(2):516-33. PMC: 3288797. DOI: 10.1007/s10439-011-0454-7. View

Chow R, Johnson M, Lopes-Martins R, Bjordal J . Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials. Lancet. 2009; 374(9705):1897-908. DOI: 10.1016/S0140-6736(09)61522-1. View

Hamblin M . Mechanisms and Mitochondrial Redox Signaling in Photobiomodulation. Photochem Photobiol. 2017; 94(2):199-212. PMC: 5844808. DOI: 10.1111/php.12864. View

Zochodne D, Ramji N, Toth C . Neuronal targeting in diabetes mellitus: a story of sensory neurons and motor neurons. Neuroscientist. 2008; 14(4):311-8. DOI: 10.1177/1073858408316175. View

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A . Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002; 3(7):RESEARCH0034. PMC: 126239. DOI: 10.1186/gb-2002-3-7-research0034. View

Vieira W, Kenzo-Kagawa B, Alvares L, Cogo J, Baranauskas V, da Cruz-Hofling M . Exploring the ability of low-level laser irradiation to reduce myonecrosis and increase Myogenin transcription after Bothrops jararacussu envenomation. Photochem Photobiol Sci. 2021; 20(4):571-583. DOI: 10.1007/s43630-021-00041-x. View

Story G, Peier A, Reeve A, Eid S, Mosbacher J, Hricik T . ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 2003; 112(6):819-29. DOI: 10.1016/s0092-8674(03)00158-2. View

10.

Holanda V, Chavantes M, Wu X, Anders J . The mechanistic basis for photobiomodulation therapy of neuropathic pain by near infrared laser light. Lasers Surg Med. 2017; 49(5):516-524. DOI: 10.1002/lsm.22628. View

11.

Pop-Busui R, Sima A, Stevens M . Diabetic neuropathy and oxidative stress. Diabetes Metab Res Rev. 2006; 22(4):257-73. DOI: 10.1002/dmrr.625. View

12.

Gandhi R, Selvarajah D . Understanding and treating painful diabetic neuropathy: time for a paradigm shift. Diabet Med. 2015; 32(6):771-7. DOI: 10.1111/dme.12755. View

13.

Krishna M, Narang H . The complexity of mitogen-activated protein kinases (MAPKs) made simple. Cell Mol Life Sci. 2008; 65(22):3525-44. PMC: 11131782. DOI: 10.1007/s00018-008-8170-7. View

14.

Lee A, Chung S . Contributions of polyol pathway to oxidative stress in diabetic cataract. FASEB J. 1999; 13(1):23-30. DOI: 10.1096/fasebj.13.1.23. View

15.

Zhai K, Liskova A, Kubatka P, Busselberg D . Calcium Entry through TRPV1: A Potential Target for the Regulation of Proliferation and Apoptosis in Cancerous and Healthy Cells. Int J Mol Sci. 2020; 21(11). PMC: 7312732. DOI: 10.3390/ijms21114177. View

16.

Manzo L, Ceragioli H, Bonet I, Nishijima C, Vieira W, Oliveira E . Magnetic, but not non-magnetic, reduced graphene oxide in spinal cord increases nociceptive neuronal responsiveness. Nanomedicine. 2017; 13(5):1841-1851. DOI: 10.1016/j.nano.2017.02.019. View

17.

Satoh J, Yagihashi S, Toyota T . The possible role of tumor necrosis factor-alpha in diabetic polyneuropathy. Exp Diabesity Res. 2003; 4(2):65-71. PMC: 2478597. DOI: 10.1155/EDR.2003.65. View

18.

Peplow P, Chung T, Baxter G . Laser photostimulation (660 nm) of wound healing in diabetic mice is not brought about by ameliorating diabetes. Lasers Surg Med. 2011; 44(1):26-9. DOI: 10.1002/lsm.21133. View

19.

Verri Jr W, Cunha T, Parada C, Poole S, Cunha F, Ferreira S . Hypernociceptive role of cytokines and chemokines: targets for analgesic drug development?. Pharmacol Ther. 2006; 112(1):116-38. DOI: 10.1016/j.pharmthera.2006.04.001. View

20.

Posten W, Wrone D, Dover J, Arndt K, Silapunt S, Alam M . Low-level laser therapy for wound healing: mechanism and efficacy. Dermatol Surg. 2005; 31(3):334-40. DOI: 10.1111/j.1524-4725.2005.31086. View