Photobiomodulation presents an anti-inflammatory effect, reflecting on the expression of receptors related to the pain process in a collagenase-induced tendinitis experimental model

Abstract

Pain associated with tendinopathy is a common and difficult to treat. A therapeutic strategy to control some chronic painful processes is the use of benzodiazepines, which act on their GABA receptors, producing a sedative and analgesic effect. Non-pharmacological approaches, such as photobiomodulation (PBM), have shown promising results in the control of inflammatory joint pain. The aim of this study was to investigate the effects of combined treatment between PBM and Diazepam (DZP) in the control of the pain process, based on the evaluation of mechanical allodynia and the expression of GABA receptors (a1 and a2), neurokinin 1 (NK1) and bradykinin (B1), comparing with the activity of myeloperoxidase (MPO) and inflammatory tissue infiltrate, in an experimental model of tendinitis. Male Wistar rats were anesthetized with 1 % inhaled isoflurane (BioChimico®, lot 008694), and tendinitis was induced by transcutaneous injection of collagenase type I into the Achilles tendon region. In the first phase, after tendinitis induction, the time course of pain sensitivity was evaluated using the mechanical allodynia test. In the second phase, the rats were distributed into seven experimental groups: Healthy Control Group (CTL) and tendinitis Untreated (NT) or treated with PBM (808 nm, 3 J, 100 mW, 107 J/cm2); treated with DZP; treated with combined therapies (PBM + DZP); pre-treated with neutral GABA receptor modulator – Flumazenil (GABA receptor antagonist) followed by DZP (FLU+DZP); and pre-treated with FLU followed by PBM (FLU+PBM). Eight hours after tendinitis induction, with the development of tissue inflammation, mechanical allodynia in the Achilles tendon was evaluated. After the various treatments, the animals were euthanized with an anaesthetic overdose and the tendons were recovered for histological and biochemical analyses. Our results showed that treatment with PBM reduced MPO activity and gene expression of B1, NK-1, GABAα2 receptors, as well as increased mechanical allodynia and GABAα1 expression. PBM + DZP also reduced MPO activity, as well as the expression of B1, GABAα₁ receptors and improved mechanical allodynia. The FLU+PBM group altered the results presented by the single treatment with PBM. Our results show that PBM modulates the pain process by improving mechanical allodynia and decreasing the gene expression of B1, NK-1 receptors, and increasing GABAα1 gene expression. These findings suggest that pain modulation by PBM in the experimental tendinitis model may be related not only to the control of inflammation but also to the regulation of the expression of B1, NK-1, GABAα1 and GABAα2 receptors.