Pain is more than merely nociception and response, but rather it encompasses emotional, behavioral and cognitive components that make up the pain experience. With the recent advances in imaging techniques, we now understand that nociceptive inputs can result in the activation of complex interactions among central sites, including cortical regions that are active in cognitive, emotional and reward functions. These sites can have a bimodal influence on the serotonergic and noradrenergic descending pain modulatory systems via communications among the periaqueductal gray, rostral ventromedial medulla and pontine noradrenergic nuclei, ultimately either facilitating or inhibiting further nociceptive inputs. Understanding these systems can help explain the emotional and cognitive influences on pain perception and placebo/nocebo effects, and can help guide development of better pain therapeutics.
Keywords: PAG; RVM; descending modulation; endogenous opioid; gabapentin; neuropathic pain; nociception; noradrenergic pain modulation; noradrenergic projections; pain matrix; serotonergic pain modulation.