Abstract
Pain is the most common symptom of osteoarthritis, and spinal glia is known to contribute to this symptom. Therapeutic ultrasound and laser therapy have been used to effectively treat osteoarthritis, with few adverse effects. Thus, this study aimed to investigate the effects of ultrasound and photobiomodulation on the symptoms and evaluate the participation of spinal glia in osteoarthritis-induced nociception in mice. Male Swiss mice were subjected to osteoarthritis induction with a 0.1-mg intra-articular injection of monosodium iodoacetate. Additionally, the mice received chronic ultrasound or photobiomodulation treatment for 21 days or a single treatment at day 14. Nociception was evaluated using von Frey filaments, and osteoarthritis symptoms were assessed by analysis of gait, joint temperature, and knee joint diameter. The role of spinal microglia and astrocytes on nociception was evaluated via an intrathecal injection of minocycline or fluorocitrate, and the spinal release of IL-1β and TNF-α was assessed by ELISA after chronic treatment with ultrasound or photobiomodulation. Our data showed that both single and chronic treatment with ultrasound or photobiomodulation attenuated the osteoarthritis-induced nociception. No differences in gait, knee joint temperature, or knee joint diameter were found. The intrathecal injection of minocycline and fluorocitrate decreased the osteoarthritis-induced nociception. There was an increase in the spinal levels of TNF-α, which was reverted by chronic ultrasound and laser treatments. These results suggest that osteoarthritis induces nociception and glial activation via spinal release of TNF-α and that the chronic treatment with ultrasound or photobiomodulation decreased nociception and TNF-α release.
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References
Martel-Pelletier J. Pathophysiology of osteoarthritis. Osteoarthritis Cartilage 2004;A:S31–3. https://doi.org/10.1016/j.joca.2003.10.002
Zhang Y, Jordan JM (2010) Epidemiology of osteoarthritis. Clin Geriatr Med 26(3):355–369. https://doi.org/10.1016/j.cger.2010.03.001
Hunter DJ, McDougall JJ, Keefe FJ (2008) The symptoms of osteoarthritis and the genesis of pain. Rheum Dis Clin North Am 34(3):623–643. https://doi.org/10.1016/j.rdc.2008.05.004
Sagar DR, Burston JJ, Hathway GJ et al (2011) The contribution of spinal glial cells to chronic pain behaviour in the monosodium iodoacetate model of osteoarthritic pain. Mol Pain 7:88. https://doi.org/10.1186/1744-8069-7-88
Woolf CJ (2011) Central sensitization: implications for the diagnosis and treatment of pain. Pain 152:S2-15. https://doi.org/10.1016/j.pain.2010.09.030
Latremoliere A, Woolf CJ (2009) Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 10(9):895–926. https://doi.org/10.1016/j.jpain.2009.06.012
Ogbonna AC, Clark AK, Gentry C, Hobbs C, Malcangio M (2013) Pain-like behaviour and spinal changes in the monosodium iodoacetate model of osteoarthritis in C57Bl/6 mice. Eur J Pain 17(4):514–526. https://doi.org/10.1002/j.1532-2149.2012.00223.x
Ogbonna AC, Clark AK, Malcangio M (2015) Development of monosodium acetate-induced osteoarthritis and inflammatory pain in ageing mice. Age 37(3):9792. https://doi.org/10.1007/s11357-015-9792-y
Milligan ED, Watkins LR (2009) Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci 10(1):23–36. https://doi.org/10.1038/nrn2533
Watkins LR, Milligan ED, Maier SF (2001) Glial activation: a driving force for pathological pain. Trends Neurosci 24(8):450–455. https://doi.org/10.1016/s0166-2236(00)01854-3
Zeng C, Li H, Yang T, Deng ZH, Yang Y, Zhang Y, Ding X, Lei GH (2014) Effectiveness of continuous and pulsed ultrasound for the management of knee osteoarthritis: a systematic review and network meta-analysis. Osteoarthr Cartil 22(8):1090–1099. https://doi.org/10.1016/j.joca.2014.06.028
Alfredo PP, Bjordal JM, Dreyer SH et al (2012) Efficacy of low level laser therapy associated with exercises in knee osteoarthritis: a randomized double-blind study. Clin Rehabil 26(6):523–533. https://doi.org/10.1177/0269215511425962
Hsieh YL (2005) Reduction in induced pain by ultrasound may be caused by altered expression of spinal neuronal nitric oxide synthase-producing neurons. Arch Phys Med Rehabil 86(7):1311–1317. https://doi.org/10.1016/j.apmr.2004.12.035
Hsieh YL (2008) Peripheral therapeutic ultrasound stimulation alters the distribution of spinal C-fos immunoreactivity induced by early or late phase of inflammation. Ultrasound Med Biol 34(3):475–486. https://doi.org/10.1016/j.ultrasmedbio.2007.09.007
Cidral-Filho FJ, Martins DF, Moré AO, Mazzardo-Martins L, Silva MD, Cargnin-Ferreira E, Santos AR (2013) Light-emitting diode therapy induces analgesia and decreases spinal cord and sciatic nerve tumour necrosis factor-α levels after sciatic nerve crush in mice. Eur J Pain 17(8):1193–1204. https://doi.org/10.1002/j.1532-2149.2012.00280.x
Zimmermann M (1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16(2):109–110. https://doi.org/10.1016/0304-3959(83)90201-4
Pitcher T, Sousa-Valente J, Malcangio M (2016) The monoiodoacetate model of osteoarthritis pain in the mouse. J Vis Exp 111:53746. https://doi.org/10.3791/53746
Hylden JL, Wilcox GL (1980) Intrathecal morphine in mice: a new technique. Eur J Pharmacol 67(2–3):313–316. https://doi.org/10.1016/0014-2999(80)90515-4
Ozgönenel L, Aytekin E, Durmuşoglu G (2009) A double-blind trial of clinical effects of therapeutic ultrasound in knee osteoarthritis. Ultrasound Med Biol 35(1):44–49. https://doi.org/10.1016/j.ultrasmedbio.2008.07.009
Coradini JG, Mattjie TF, Bernardino GR et al (2014) Comparison of low level laser, ultrasonic therapy and association in joint pain in Wistar rats. Rev Bras Reumatol 54:7–12. https://doi.org/10.1016/j.rbr.2014.01.001
Turner TA (1991) Thermography as an aid to the clinical lameness evaluation. Vet Clin North Am Equine Pract 7(2):311–338. https://doi.org/10.1016/s0749-0739(17)30502-3
Makii Y, Asaka M, Setogawa S et al (2018) Alteration of gait parameters in a mouse model of surgically induced knee osteoarthritis. J Orthop Surg 26(2):2309499018768017. https://doi.org/10.1177/2309499018768017
Jacobs BY, Kloefkorn HE, Allen KD (2014) Gait analysis methods for rodent models of osteoarthritis. Curr Pain Headache Rep 18(10):456. https://doi.org/10.1007/s11916-014-0456-x
Johnson VL, Hunter DJ (2014) The epidemiology of osteoarthritis. Best Pract Res Clin Rheumatol 28(1):5–15. https://doi.org/10.1016/j.berh.2014.01.004
Guzman RE, Evans MG, Bove S, Morenko B, Kilgore K (2003) Mono-iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints: an animal model of osteoarthritis. Toxicol Pathol 31(6):619–624. https://doi.org/10.1080/01926230390241800
van der Kraan PM, Vitters EL, van de Putte LB, van den Berg WB (1989) Development of osteoarthritic lesions in mice by “metabolic” and “mechanical” alterations in the knee joints. Am J Pathol 135(6):1001–1014
Jia L, Wang Y, Chen J, Chen W (2016) Efficacy of focused low-intensity pulsed ultrasound therapy for the management of knee osteoarthritis: A randomized, double blind, placebo-controlled trial. Sci Rep 6:1–9. https://doi.org/10.1038/srep35453
Johns LD (2002) Nonthermal effects of therapeutic ultrasound: The frequency resonance hypothesis. J Athl Train 37:293–299
Chen YW, Tzeng JI, Huang PC, Hung CH, Shao DZ, Wang JJ (2015) Therapeutic ultrasound suppresses neuropathic pain and upregulation of substance P and neurokinin-1 receptor in rats after peripheral nerve injury. Ultrasound Med Biol 41(1):143–150. https://doi.org/10.1016/j.ultrasmedbio.2014.07.022
Hung CH, Huang PC, Tzeng JI, Wang JJ, Chen YW (2016) Therapeutic ultrasound and treadmill training suppress peripheral nerve injury-induced pain in rats. Phys Ther 96(10):1545–1553. https://doi.org/10.2522/ptj.20140379
Leong DJ, Zhang H, Xu L et al (2013) Therapeutic ultrasound: Osteoarthritis symptom-modification and potential for disease modification. J Surgery 1(2):5
Tsui PH, Wang SH, Huang CC (2005) In vitro effects of ultrasound with different energies on the conduction properties of neural tissue. Ultrasonics 43(7):560–565. https://doi.org/10.1016/j.ultras.2004.12.003
Pan H, Zhou Y, Izadnegahdar O, Cui J, Deng CX (2005) Study of sonoporation dynamics affected by ultrasound duty cycle. Ultrasound Med Biol 31(6):849–856. https://doi.org/10.1016/j.ultrasmedbio.2005.03.014
da Silva Junior EM, Mesquita-Ferrari RA, França CM et al (2017) Modulating effect of low intensity pulsed ultrasound on the phenotype of inflammatory cells. Biomed Pharmacother 96:1147–1153. https://doi.org/10.1016/j.biopha.2017.11.108
Straub SJ, Johns LD, Howard SM (2008) Variability in effective radiating area at 1 MHz affects ultrasound treatment intensity. Phys Ther 88(1):50–57. https://doi.org/10.2522/ptj.20060358
Rayegani SM, Raeissadat SA, Heidari S, Moradi-Joo M. Safety and effectiveness of low-level laser therapy in patients with knee osteoarthritis: A systematic review and meta-analysis. J Lasers Med Sci 2017;8(1):S12-S19. https://doi.org/10.15171/jlms.2017.s3
de Freitas LF, Hamblin MR (2016) Proposed mechanisms of photobiomodulation or low-level light therapy. IEEE J Sel Top Quantum Electron 22(3):7000417. https://doi.org/10.1109/JSTQE.2016.2561201
Cotler HB, Chow RT, Hamblin MR, Carroll J. The use of low level laser therapy (LLLT) for musculoskeletal pain. MOJ Orthop Rheumatol 2015;2(5):00068. https://doi.org/10.15406/mojor.2015.02.00068
Chow RT, David MA, Armati PJ (2007) 830 nm laser irradiation induces varicosity formation, reduces mitochondrial membrane potential and blocks fast axonal flow in small and medium diameter rat dorsal root ganglion neurons: implications for the analgesic effects of 830 nm laser. J Peripher Nerv Syst 12(1):28–39. https://doi.org/10.1111/j.1529-8027.2007.00114.x
Chow R, Armati P, Laakso EL, Bjordal JM, Baxter GD (2011) Inhibitory effects of laser irradiation on peripheral mammalian nerves and relevance to analgesic effects: a systematic review. Photomed Laser Surg 29(6):365–381. https://doi.org/10.1089/pho.2010.2928
Andrade P, Visser-Vandewalle V, Hoffmann C, Steinbusch HWM, Daemen MA et al (2011) Role of TNF-alpha during central sensitization in preclinical studies. Neurol Sci 32:757. https://doi.org/10.1007/s10072-011-0599-z
Bove SE, Calcaterra SL, Brooker RM et al (2003) Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis. Osteoarthr Cartil 11(11):821–830. https://doi.org/10.1016/s1063-4584(03)00163-8
Favero M, Ramonda R, Goldring MB, Goldring SR, Punzi L (2015) Early knee osteoarthritis RMD Open 1(1):e000062. https://doi.org/10.1136/rmdopen-2015-000062
Hsieh YL, Chen HY, Yang CC (2018) Early intervention with therapeutic low-intensity pulsed ultrasound in halting the progression of post-traumatic osteoarthritis in a rat model. Ultrasound Med Biol 44(12):2637–2645. https://doi.org/10.1016/j.ultrasmedbio.2018.08.007
Wang P, Liu C, Yang X et al (2014) Effects of low-level laser therapy on joint pain, synovitis, anabolic, and catabolic factors in a progressive osteoarthritis rabbit model. Lasers Med Sci 29(6):1875–1885. https://doi.org/10.1007/s10103-014-1600-x
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This work was supported by Fundação de Amparo à Pesquisa do Estado de Minas (FAPEMIG), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) [Grant 001].
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The experiments were approved by the Animal Care and Use Committee at the Federal University of Alfenas, in Alfenas, Minas Gerais, Brazil (protocol number 49/2017).
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Malta, I., Moraes, T., Elisei, L. et al. Investigation of the effects of therapeutic ultrasound or photobiomodulation and the role of spinal glial cells in osteoarthritis-induced nociception in mice. Lasers Med Sci 37, 1687–1698 (2022). https://doi.org/10.1007/s10103-021-03418-7
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DOI: https://doi.org/10.1007/s10103-021-03418-7