The Effect of Low-Level Light Therapy on Capsaicin-Induced Peripheral and Central Sensitization in Healthy Volunteers: A Double-Blinded, Randomized, Sham-Controlled Trial
Tóm tắt
Several clinical trials have demonstrated that low-level light therapy (LLLT), a method of photobiomodulation, is an effective analgetic treatment. However, the mechanism of action has not yet been finally clarified. In particular, unanswered questions include whether it only affects peripheral or whether it also affects the spinal or supraspinal level. This study aimed to evaluate the effect of low-level light therapy on primary and secondary hyperalgesia in a human pain model. This study was planned as a randomized, sham-controlled, and double-blinded trial with repeated measures within subject design. Capsaicin was applied on both forearms of ten healthy volunteers to induce peripheral and central sensitization. One forearm was treated with low-level light therapy; the other served as sham control. Low-level light therapy significantly increased the mechanical pain threshold, heat pain threshold, and decreased pain intensity. Our data indicate that low-level light therapy is effective at reducing the heat and mechanical pain threshold in a human pain model, pointing to a significant modulating effect on peripheral and central sensitization. These effects—especially in the absence of reported side effects—make low-level light therapy a promising tool in pain management. The application of low-level light therapy to treat chronic pain should be considered for further clinical trials.
Tài liệu tham khảo
De Freitas LF, Hamblin MR. Proposed mechanisms of photobiomodulation or low-level light therapy. IEEE J Sel Top Quantum Electron. 2016;22:348–64.
Gold MS, Gebhart GF. Nociceptor sensitization in pain pathogenesis. Nat Med. 2010;16:1248–57.
Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152:S2–15.
Maihofner C, Nickel FT, Seifert F. Neuropathic pain and neuroplasticity in functional imaging studies. Schmerz. 2010;24:137–45.
Vollert J, Magerl W, Baron R, et al. Pathophysiological mechanisms of neuropathic pain: comparison of sensory phenotypes in patients and human surrogate pain models. Pain. 2018;159:1090–102.
Jimenez-Andrade JM, Bloom AP, Stake JI, et al. Pathological sprouting of adult nociceptors in chronic prostate cancer-induced bone pain. J Neurosci Off J Soc Neurosci. 2010;30:14649–566.
Treede RD, Meyer RA, Raja SN, et al. Peripheral and central mechanisms of cutaneous hyperalgesia. Prog Neurobiol. 1992;38:397–421.
Hansen MS, Wetterslev J, Pipper CB, et al. The area of secondary hyperalgesia following heat stimulation in healthy male volunteers: inter- and intra-individual variance and reproducibility. PLoS ONE. 2016;11:e0155284.
Arendt-Nielsen L, Morlion B, Perrot S, et al. Assessment and manifestation of central sensitisation across different chronic pain conditions. Eur J Pain. 2018;22:216–41.
Esper MA, Nicolau RA, Arisawa EA. The effect of two phototherapy protocols on pain control in orthodontic procedure–a preliminary clinical study. Lasers Med Sci. 2011;26:657–63.
Langella LG, Casalechi HL, Tomazoni SS, et al. Photobiomodulation therapy (PBMT) on acute pain and inflammation in patients who underwent total hip arthroplasty—a randomized, triple-blind, placebo-controlled clinical trial. Lasers Med Sci. 2018;33:1933–40.
Leal-Junior EC, Johnson DS, Saltmarche A, et al. Adjunctive use of combination of super-pulsed laser and light-emitting diodes phototherapy on nonspecific knee pain: double-blinded randomized placebo-controlled trial. Lasers Med Sci. 2014;29:1839–47.
Lima ACG, Fernandes GA, Gonzaga IC, et al. Low-level laser and light-emitting diode therapy for pain control in hyperglycemic and normoglycemic patients who underwent coronary bypass surgery with internal mammary artery grafts: a randomized, double-blind study with follow-up. Photomed Laser Surg. 2016;34:244–51.
Strouthos I, Chatzikonstantinou G, Tselis N, et al. Photobiomodulation therapy for the management of radiation-induced dermatitis. Strahlenther Onkol. 2017;193:491–8.
Fitzpatrick TB. Ultraviolet-induced pigmentary changes: benefits and hazards. Curr Probl Dermatol. 1986;15:25–38.
Baumann TK, Simone DA, Shain CN, et al. Neurogenic hyperalgesia: the search for the primary cutaneous afferent fibers that contribute to capsaicin-induced pain and hyperalgesia. J Neurophysiol. 1991;66:212–27.
Koltzenburg M, Lundberg LE, Torebjörk HE. Dynamic and static components of mechanical hyperalgesia in human hairy skin. Pain. 1992;51:207–19.
Lin Q, Wu J, Willis WD. Dorsal root reflexes and cutaneous neurogenic inflammation after intradermal injection of capsaicin in rats. J Neurophysiol. 1999;82:2602–11.
Lotsch J, Walter C, Zunftmeister M, et al. A data science approach to the selection of most informative readouts of the human intradermal capsaicin pain model to assess pregabalin effects. Basic Clin Pharmacol Toxicol. 2020;126:318–31.
Muley MM, Krustev E, Mcdougall JJ. Preclinical assessment of inflammatory pain. CNS Neurosci Ther. 2016;22:88–101.
Zheng Z, Bai L, O’loughlan M, et al. Does electroacupuncture have different effects on peripheral and central sensitization in humans: a randomized controlled study. Front Integr Neurosci. 2019;13:61.
Pfau D, Klein T, Blunk JA, et al. QST—Quantitative Sensorische Testung—Handlungsanweisung für den Untersucher. Lehrstuhl für Neurophysiologie. Mannheim: Universitätsmedizin Mannheim; 2010.
Rolke R, Baron R, Maier C, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain. 2006;123:231–43.
Ali Z, Meyer R, Campbell JN. Secondary hyperalgesia to mechanical but not heat stimuli following a capsaicin injection in hairy skin. Pain. 1996;68:401–11.
Fritz CO, Morris PE, Richler JJ. Effect size estimates: current use, calculations, and interpretation. J Exp Psychol Gen. 2012;141:2–18.
Bartlett MS. The use of transformations. Biometrics. 1947;3:39–52.
Cidral-Filho FJ, Mazzardo-Martins L, Martins DF, et al. Light-emitting diode therapy induces analgesia in a mouse model of postoperative pain through activation of peripheral opioid receptors and the l-arginine/nitric oxide pathway. Lasers Med Sci. 2014;29:695–702.
Laraia EMS, Silva IS, Pereira DM, et al. Effect of low-level laser therapy (660 nm) on acute inflammation induced by tenotomy of Achilles tendon in rats. Photochem Photobiol. 2012;88:1546–50.
Martins DF, Turnes BL, Cidral-Filho FJ, et al. Light-emitting diode therapy reduces persistent inflammatory pain: role of interleukin 10 and antioxidant enzymes. Neuroscience. 2016;324:485–95.
Li WH, Fassih A, Binner C, et al. Low-level red LED light inhibits hyperkeratinization and inflammation induced by unsaturated fatty acid in an in vitro model mimicking acne. Lasers Surg Med. 2018;50:158–65.
Cidral-Filho F, Martins D, Moré A, et al. 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. 2013;17:1193–204.
Brack A, Labuz D, Schiltz A, et al. Tissue monocytes/macrophages in inflammation: hyperalgesia versus opioid-mediated peripheral antinociception. Anesthesiol J Am Soc Anesthesiol. 2004;101:204–11.
Budzinski M, Misterek K, Gumulka W, et al. Inhibition of inducible nitric oxide synthase in persistent pain. Life Sci. 2000;66:301–5.
Hoheisel U, Unger T, Mense S. The possible role of the NO-cGMP pathway in nociception: different spinal and supraspinal action of enzyme blockers on rat dorsal horn neurones. Pain. 2005;117:358–67.
Schmidtko A, Gao W, Konig P, et al. cGMP produced by NO-sensitive guanylyl cyclase essentially contributes to inflammatory and neuropathic pain by using targets different from cGMP-dependent protein kinase I. J Neurosci Off J Soc Neurosci. 2008;28:8568–76.
Karu TI, Pyatibrat LV, Afanasyeva NI. Cellular effects of low-power laser therapy can be mediated by nitric oxide. Lasers Surg Med. 2005;36:307–14.
Lee HI, Lee SW, Kim SY, et al. Pretreatment with light-emitting diode therapy reduces ischemic brain injury in mice through endothelial nitric oxide synthase-dependent mechanisms. Biochem Biophys Res Commun. 2017;486:945–50.
Pigatto GR, Silva CS, Parizotto NA. Photobiomodulation therapy reduces acute pain and inflammation in mice. J Photochem Photobiol B. 2019;196:111513.
Zheng Z, Gibson SJ, Khalil Z, et al. Age-related differences in the time course of capsaicin-induced hyperalgesia. Pain. 2000;85:51–8.
Opree A, Kress M. Involvement of the proinflammatory cytokines tumor necrosis factor-alpha, IL-1 beta, and IL-6 but not IL-8 in the development of heat hyperalgesia: effects on heat-evoked calcitonin gene-related peptide release from rat skin. J Neurosci Off J Soc Neurosci. 2000;20:6289–93.
Wagner R, Janjigian M, Myers RR. Anti-inflammatory interleukin-10 therapy in CCI neuropathy decreases thermal hyperalgesia, macrophage recruitment, and endoneurial TNF-alpha expression. Pain. 1998;74:35–42.