Cortical Modulation of Nociception.

Nociception is the neuronal process of encoding noxious stimuli and could be modulated at peripheral, spinal, brainstem, and cortical levels. At cortical levels, several areas including the anterior cingulate cortex (ACC), prefrontal cortex (PFC), ventrolateral orbital cortex (VLO), insular cortex (IC), motor cortex (MC), and somatosensory cortices are involved in nociception modulation through two main mechanisms: (i) a descending modulatory effect at spinal level by direct corticospinal projections or mostly by activation of brainstem structures (i.e. periaqueductal grey matter (PAG), locus coeruleus (LC), the nucleus of raphe (RM) and rostroventral medulla (RVM)); and by (ii) cortico-cortical or cortico-subcortical interactions. This review summarizes evidence related to the participation of the aforementioned cortical areas in nociception modulation and different neurotransmitters or neuromodulators that have been studied in each area. Besides, we point out the importance of considering intracortical neuronal populations and receptors expression, as well as, nociception-induced cortical changes, both functional and connectional, to better understand this modulatory effect. Finally, we discuss the possible mechanisms that could potentiate the use of cortical stimulation as a promising procedure in pain alleviation.