Photobiomodulation Therapy Improves Acute Inflammatory Response in Mice: the Role of Cannabinoid Receptors/ATP-Sensitive K+ Channel/p38-MAPK Signalling Pathway

Abstract

Although photobiomodulation therapy (PBM) has been applied clinically for the treatment of pain and inflammation, wound healing, sports and soft tissue injuries, as well as to repair injured spinal cords and peripheral nerves, it remains unclear which molecular substrates (receptor) are implicated in the cellular mechanisms of PBM. Here, we reported that PBM (660 nm, 30 mW, 0.06 cm, 50 J/cm, plantar irradiation) significantly inhibited carrageenan-induced paw oedema, but not noxious thermal response, through positive modulation to both CB1 and CB2 cannabinoid receptors. The use of CB1 antagonist AM281 or CB2 antagonist AM630 significantly reversed the anti-inflammatory effect of PBM. Analysis of signalling pathway downstream of cannabinoid receptors activation reveals that anti-inflammatory effects of PBM depend, in great extent, on its ability to activate ATP-dependent K channels and p38 mitogen-activated protein kinase. Moreover, PBM therapy significantly reduced the levels of pro-inflammatory cytokine IL-6 in both paw and spinal cord, and restored the reduction of the level of anti-inflammatory cytokine IL-10 in spinal cord after carrageenan injection. Unlike the potent cannabinoid receptor agonist (WIN 55212-2), PBM did not exert any CNS-mediated effects in the tetrad assay. Finally, PBM does not reduce inflammation and noxious thermal response induced by LPS and zymosan, a TLR4 and TLR2/dectin-1 ligand, respectively. Thus, cannabinoid receptors and, possibly, the endocannabinoid system, represent an important site of action of PBM that opens the possibility of complementary and nonpsychotropic therapeutic interventions in clinical practice. Graphical Abstract ᅟ.

Hydrogen sulfide modulates IL-6/STAT3 pathway and inhibits oxidative stress, inflammation, and apoptosis in rat model of methotrexate hepatotoxicity

“…34,35 Previous studies also revealed that K ATP channel activators produced their antioxidant, anti-inflammation, antiapoptotic effects by causing significant decreases in IL-6 production. 36,37 Other studies showed that IL-6 inhibited eNOS expression in acute-phase inflammatory response either directly or through activation of IL-6/STAT3 pathway. [38][39][40] Besides, prior investigations showed that activation of TRPV1 by capsaicin resulted in significant inhibition of constitutive and IL-6-induced activation of STAT3.…”

Low‐Intensity Photobiomodulation Decreases Neuropathic Pain in Paw Ischemia‐Reperfusion and Spared Nervus Ischiadicus Injury Experimental Models

“…In this context, the fact that infrared LED was effective against mechanical and thermal hypersensitivity to cold on each day of treatment, which is clinically interesting, raises a precedent that would justify investment in research studying patients affected by this syndrome. Additionally, the therapeutic effects both on the reduction of mechanical hypersensitivity and on the cold thermal test suggest the activation of different receptor populations and neural fibers involved in the process of pain, such as those suggested by previous studies …”

“…Additionally, the therapeutic effects both on the reduction of mechanical hypersensitivity and on the cold thermal test suggest the activation of different receptor populations and neural fibers involved in the process of pain, such as those suggested by previous studies. 12,63,64 It is important to further investigate the type of device used and the location of LED application. In this study, we used a device with a multiple-LED array, and the site of application was the entire body of the animal, which is primarily how this study differs from the literature.…”

Analysis of lncRNAs Expression Profiles in Hair Follicle of Hu Sheep Lambskin

“…Therefore, ATP1B4 is not only the source gene of TCONS_00279168 but also its target gene. ATP1B4 is a member of ATPase Na+/K+ transporting family, which is believed to contribute to the activity of the MAPK signaling pathway, which is well supported by the studies in humans [ 53 , 54 ]. Furthermore, ATP1B4 , as an important member of ATPase Na+/K+ transporting beta M family, which is involved in the regulation of gene expression level in TGF-β signaling pathway as exemplified by an increase of expression of inhibitory Smad7.…”