# Percutaneous Needle Electrolysis Accelerates Functional Muscle Regeneration in Mice
## 1 Introduction  
Modern medicine has experienced continual advancements in percutaneous galvanic current delivery for musculoskeletal injuries [1, 2]. The clinical use of the same comprises oncological treatments [3], known as electrolytic ablation, and chronic tendinitis [4, 5], known as percutaneous needle electrolysis (PNE). The clinical use of electric currents has also been found to accelerate muscle regeneration in humans [6].  
Additionally, numerous in vivo as well as ex vivo studies have shown that cells can respond directionally to the application of electrical fields. This phenomenon is known as electrotaxis or galvanotaxis (reviewed by [PERSON] et al. [7]). Vascular endothelial cells also respond to the phenomenon of electrotaxis, thereby enhancing angiogenesis [8]. Additionally, cells involved in inflammatory or immune responses, such as lymphocytes [9] or macrophages [10], are also attracted to electrical currents. Furthermore, the migration mediated by electric currents involves cAMP and the G protein [11, 12, 13]. Generally, cAMP and G proteins trigger many other events of cell signal transduction [14, 15]. Therefore, electric currents can activate many specific cellular capacities.  
[PERSON] et al. [16] assessed the effect of the application of PNE on a model of muscle lesions in rat by injecting intramuscular notexin. A small amount of intramuscular notexincaused a lesion of the whole muscle. The main results observed were that the application of a galvanic current induced a decrease in pro-inflammatory mediators (TNF-\(\alpha\) and IL-1\(\beta\)) and an increased expression of anti-inflammatory proteins (PPAR-\(\gamma\)), as well as an increase in both the vascular endothelial growth factor (VEGF) and the VEGF-R1 receptor. More recently, [PERSON] et al. [17] replicated the experiment of [PERSON] et al., confirming that when applying PNE after injury, an increase in anti-inflammatory mediators and a reduction in pro-inflammatory mediators were observed. These authors reported that an overall promoted muscle regeneration was observed. Notexin creates a generalized lesion of the treated muscle. [PERSON] et al. [18] conducted a comparative study between the two myolytic agents; notexin and bupivacaine. The notexin caused a greater muscle injury and was more difficult to regenerate than with the bupicavaine. All previous studies used notexin to cause extensive muscle injury. However, muscle lesions in humans are usually localized and rarely extensive. In this study, bupivacaine has been used in order to produce very localized muscle injuries.  
The neuromuscular synapse releases vesicles of acetylcholine as a neurotransmitter. These vesicles can be released massively, generating an action potential in the muscle fiber, or spontaneously. In spontaneous neurotransmission, isolated vesicles are released and stochastically distributed over time [19]. An electromyographic-recording needle can record the spontaneous release of vesicles from several dozen muscle fibers [20]. Electromyography devices usually incorporate a transducer that converts the electrical record into sound. Finally, the electromyographic record of spontaneous neuromuscular release is identified as a characteristic \"endplate noise\" [20; 21]. No previous study has evaluated the restoration of neurotransmission after muscle injury. In this study, endplate noise was recorded as an indicator of the fully functional recovery of muscle fibers.  
The purpose of this study was to determine the action of percutaneous needle electrolysis in muscle regeneration, by endplate noise recording, and functional reinnervation in an animal model based on bupivacaine-induced localized muscle injury.