Figure 1

Basis of the gate control theory. (A) General view. (B) Pain inhibition complex in detail. In short, the stimulation of the PAG in the midbrain activates neurons that are able to release enkephalins and project to the brainstem, specifically in the raphe nuclei (NRM) where 5-HT (serotonin) is released and descends to the dorsal horn of the spinal cord. The 5-HT is able to activate interneurons that, by their turn, release endogenous opioid neurotransmitters (either enkephalin or dynorphin in (B)), which activate the opioid receptors on the axons of incoming C and A-δ fibers that transmit the pain signals from nociceptors activated in the periphery. 5-HT = 5-hydroxytriptamine; NRM = nucleus raphe magnus; PAG = periaqueductal gray matter.