Chronic pain is an important public health issue. Moreover, its adequate management is still considered a major clinical problem,\nmainly due to its incredible complexity and still poorly understood pathophysiology. Recent scientific evidence coming from\nneuroimaging research, particularly functional magnetic resonance (fMRI) and positron emission tomography (PET) studies,\nindicates that chronic pain is associated with structural and functional changes in several brain structures that integrate\nantinociceptive pathways and endogenous modulatory systems. Furthermore, the last two decades have witnessed a huge increase\nin the number of studies evaluating the clinical effects of noninvasive neuromodulatory methods, especially transcranial magnetic\nstimulation (TMS) and transcranial direct current stimulation (tDCS), which have been proved to effectively modulate the cortical\nexcitability, resulting in satisfactory analgesic effects with minimal adverse events. Nevertheless, the precise neuromechanisms\nwhereby such methods provide pain control are still largely unexplored. Recent studies have brought valuable information\nregarding the recruitment of different modulatory systems and related neurotransmitters, including glutamate, dopamine, and\nendogenous opioids. However, the specific neurocircuits involved in the analgesia produced by those therapies have not been fully\nelucidated. This review focuses on the current literature correlating the clinical effects of noninvasive methods of brain stimulation\nto the changes in the activity of endogenous modulatory systems.
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