## 2 Therapeutic Methodologies
### Electotherapy  
Electotherapy is applied for several physiological effects, namely pain relief, muscle work and relaxation, stimulation of tissue flows, tissue regeneration and transdermal medicinal products (drugs) application. The most used current for this therapeutic purpose is the transcutaneous electrical nerve stimulation, TENS. The nature of these currents allows the reduction of skin impedance and the stimulation of the transport of ionic substances, for very low current values, in the order of mA units (below 5 mA), being, therefore, a safe and painless process. Pain can be clinically present in several ways and associated with multiple symptoms and can be characterized as acute (symptomatic) and chronic (pathological). Acute pain is usually the result of an injury, while chronic pain has no biological function and remains even after healing, being itself considered a disease. Each physiotherapy technique has a neurophysiological explanation with its own mechanisms of action. The inhibitory modulation of pain occurs with the reduction of peripheral and central stimuli that sensitize the nervous system [19]. In 1965, [PERSON] and [PERSON] published the first interpretation of the pain phenomenon with the designation of \"Gate-control theory of pain\". This theory was based on physiology and associated with sensory aspects and psychological aspects of pain perception. The theory of the pain gate introduced the concept of the experience of pain as not being the result of a linear process that begins with the stimulation of pain transmission routes to the peripheral nervous system and ends with the experience of pain in the central nervous system. What really happens is that the nerve impulses that potentiate the pain signal in the peripheral nervous system, are subject to a few modulations in the spinal cord before the pain experience is transmitted to the central nervous system. According to the authors, the gate mechanism is modulated by emotions, cognitive state, and past experiences. A painful stimulus is detected by pain receptors, called nociceptors, which can be of three types: thermal, mechanical and polymodal (simultaneous detection of mechanical and thermal stimulation). The nociceptive fibers, conducting the stimulus to the central nervous system, more specifically to the spinal cord, can be A8 (fast response) or C (slow response). From the spinal cord, it goes to the brainstem, thalamus and finally the cerebral cortex where pain perception is triggered [20]. Another theory, the endogenous opioids system, is associated with the fact that the nervous system has several receptors for opioid substances, beta-endorphin, dymorphisms and met- and leu- enkephalins [21]. Electrical stimulation can lead to the release of endogenous opioid substances and decrease the sensation of pain. The release of opioids is also used to explain the action of low-frequency TENS (2 to 5 Hz) [22]. Iontophoresis is a non-invasive electrotherapy method, quite common in physical medicine and rehabilitation, for transdermal transmission of drugs, based on the transfer of charged molecules, using low-intensity electric current. The advantages of its use refer to the faster release of the drug into the skin, the passage of macromolecules and better control of the dose to be administered. Inverse iontophoresis has also been studied to allow the extraction of molecules from the skin, having been applied in glucose monitoring studies [23]. It is also a technique with potential in the diagnosis and monitoring [24] of a noninvasive form of clinically important molecules in the human body [25]. Iontophoresis occurs by the application of an electric field, creating a potential difference between two electrodes, one with positive polarity (anode) and the other with negative polarity (cathode). These electrodes are placed in a certain position that prevents current from passing through the cardiothoracic box. The maximum limit of the current applied before the patient manifests physical discomfort is 0.5 mA/cm\({}^{2}\).