Methods to focalize noninvasive electrical brain stimulation: principles and future clinical development for the treatment of pain.

There has been increased interest in noninvasive brain stimulation (NIBS) as a technique to investigate and treat neuropsychiatric disorders [1,2]. Usually, NIBS is targeted to specific dysfunctional cortical areas, as the case for prefrontal cortex stimulation in mood disorders [3], or regions presumed to modulate dysfunctional areas, as the case for primary motor cortex (M1) stimulation to influence thalamic activity in chronic pain syndromes [4]. The neurophysiological effects are based on modulation of cortical excitability. NIBS, using common and validated protocols, is considered safe and painless and is not associated with severe adverse effects [5]. The two main techniques of NIBS that have been currently explored are trans cranial magnetic stimulation and transcranial direct current stimulation (tDCS), although additional approaches such as transcranial alternating current stimulation, cranial electrotherapy stimulation/transcranial pulsed current stimulation and nonelectrical modalities are under investigation [6,7]. Although transcranial magnetic stimulation is an effective technique to induce focal changes in cortical excitability, it is relativity costly, requires wall-powered equipment to produce the required stimulation intensities and it may lead to seizures. The recent development of tDCS provides a more cost-effective, portable and simple approach to NIBS [3]. This technique has shown to induce significant effects on neuroplasticity as shown by animal models and human studies [8–10]. While almost every individual has experienced pain – which in some situations, such as in acute conditions, can be advantageous to protect against further damage – the field of medicine is still dedicating massive amounts of resources and time in order to free humanity from this form of unpleasant condition, especially in chronic syndromes. In fact, for chronic refractory pain, most forms of therapeutic efforts provide only transient relief for many patients without much solution addressing the fundamental basis of the problem. The simplistic conception of pain as just a reflexive response to physical damage has evolved in the last century, nowadays, there is more focus on the brain’s role as the main modulatory organ for perception, response and, thus, a possible solution of the problem by itself. Although the central mechanism involved in chronic pain remains under investigation, increasing evidence supports the use of brain stimulation in the treatment of chronic refractory pain. There has been a great interest in exploring tDCS as a CNS-based therapeutic tool for the treatment of chronic pain. Such interest has been an evolution from the first Methods to focalize noninvasive electrical brain stimulation: principles and future clinical development for the treatment of pain