Galvanic current activates the NLRP3 inflammasome to promote Type I collagen production in tendon

Abstract

The NLRP3 inflammasome coordinates inflammation in response to different pathogen- and damage-associated molecular patterns, being implicated in different infectious, chronic inflammatory, metabolic and degenerative diseases. In chronic tendinopathic lesions, different non-resolving mechanisms produce a degenerative condition that impairs tissue healing and which therefore complicates their clinical management. Percutaneous needle electrolysis consists of the application of a galvanic current and is an emerging treatment for tendinopathies. In the present study, we found that galvanic current activates the NLRP3 inflammasome and induces an inflammatory response that promotes a collagen-mediated regeneration of the tendon in mice. This study establishes the molecular mechanism of percutaneous electrolysis that can be used to treat chronic lesions and describes the beneficial effects of an induced inflammasome-related response.

Application of Percutaneous Needle Electrolysis Does Not Elicit Temperature Changes: An In Vitro Cadaveric Study

“…Previous explanations of tissue repair mechanisms for PNE were based on Na OH release and local pH alkalization [ 23 ]. However, a recent study has rejected this hypothesis, opening the option to other possible explanations, such as a potential inflammatory response mediated by NLRP3 inflammasome [ 24 ]. Galvanic current is also applied in high doses as electrolytic ablation by surgeons applying 100 times higher doses [ 25 ] than in PNE, doses which physiotherapy galvanic electronic devices cannot achieve.…”

“…In fact, high-intensity doses for long exposure times or repeated high-intensity impacts can produce greater necrosis in the tissue, not associated with tissue recovery [ 25 ]. Therefore, high doses are not advisable for clinical practice, as has been previously demonstrated in a recent study [ 24 ]. Considering that temperature is not a differential or limiting factor for calculating the treatment dose since no changes are obtained, formulas to calculate the most appropriate dose for each type of human tissue according to the tissue damage are needed to reduce treatment variability.…”

A modern interpretation of traditional galvanic current: percutaneous needle electrolysis therapy

“…In addition, the ability of galvanic current to enhance drug delivery through the skin has led to its application in localized pharmacological treatments for musculoskeletal conditions. 3…”

Focus on the Role of the NLRP3 Inflammasome in Multiple Sclerosis: Pathogenesis, Diagnosis, and Therapeutics

“…NLRP3 inflammasome was initially characterized in Muckle-Wells syndrome, which is an autoinflammatory disease (Martinon et al, 2002 ). As a common inflammasome, the NLRP3 inflammasome senses a wide range of danger- and pathogen-associated molecular patterns (DAMPs and PAMPs, respectively), and participates in a myriad of immune and inflammatory diseases (Peñin-Franch et al, 2022 ). There are three components of the NLRP3 inflammasome: NLRP3 protein (sensor), apoptosis-associated specklike protein containing a caspase-activation and recruitment domain (ASC) (adaptor), and pro-caspase-1 (effector) (Broz and Dixit, 2016 ) ( Figure 1 ).…”