Figure 1.

Top–down corticospinal pain and emotion network model. Afferent sensory neurons carry information towards the dorsal root ganglion followed by the somatic and visceral nuclei in the dorsal horn. These sensory neurons project directly to the thalamus but also indirectly to the ACC via the parabrachial nuclei (PB) and amygdala. Conversely, the ACC can modulate spinal dorsal horn neurons both directly or indirectly via the periaqueductal grey (PAG) and rostral ventromedial medulla (RVM). Direct transmission is mediated by glutamate, while indirect pathways involve serotonin (5-HT), which produces facilitatory effects on nociceptive transmission. Artificial stimulation of excitatory ACC neurons can enhance nociception, but activation of inhibitory interneurons produces an analgesic effect suggesting the importance of E/I balance. Beyond this, the ACC also is believed to integrate pain-related sensory and emotional information and relay it to the prefrontal cortex (PFC). Blue arrows indicate ascending projections from the dorsal horn to higher brain structures. Dashed red arrows and the solid red arrow indicate the indirect and direct descending pathway from the ACC to the dorsal horn, respectively. Abbreviations: PFC, prefrontal cortex; ACC, anterior cingulate cortex; IC, insular cortex; S1, somatosensory cortex 1; S1, somatosensory cortex 2; E/I, excitation/inhibition.