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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

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Abstract

Light-emitting diode therapy (LEDT) has been clinically used as an alternative to low-level laser therapy; nevertheless, the molecular basis for LEDT effects remains unclear. The objective of this study was to evaluate the analgesic effect of LEDT in the mouse plantar incision (PI) model of postoperative pain, as well as to investigate some of the possible mechanisms involved in this effect, i.e., peripheral and central opioid receptors; migration of opioid-containing leukocytes to PI site and the l-arginine/nitric oxide (NO) pathway. To that end, mice were subjected to PI and treated with LEDT (950 nm, 80 mW/cm2, 1 through 13 J/cm2). Mechanical hypersensitivity was assessed as withdrawal frequency percentage to 10 presentations of a 0.4-g von Frey filament. In addition, the animals were pretreated with systemic (i.p.), intra-plantar (i.pl.), or intrathecal injection (i.t) of naloxone (a nonselective opioid receptor antagonist; 1 mg/kg, i.p.; 5 μg/right paw or 5 μg/site, respectively) or a systemic injection of fucoidin (100 μg/mouse, i.p., an inhibitor of leukocyte rolling through binding to l- and p-selectins). Our results demonstrate, for the first time, that LEDT induced a dose–response analgesic effect in the model of PI in mice. At the dose of 9 J/cm2 LEDT presented the most significant results through (1) activation of peripheral opioid receptors which involve, at least partially, the recruitment of opioid-containing leukocytes to the PI site and; (2) activation of the l-arginine/NO pathway. These results extend previous literature data and suggest that LEDT might be useful in the treatment of postoperative pain.

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Acknowledgments

This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC), Brazil.

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Correspondence to Adair R. S. Santos.

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Cidral-Filho, F.J., Mazzardo-Martins, L., Martins, D.F. 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 29, 695–702 (2014). https://doi.org/10.1007/s10103-013-1385-3

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