[Molecular mechanisms of NMDA receptor-MAPK-CREB pathway underlying the involvement of the anterior cingulate cortex in pain-related aversion].

The pain experience includes a sensory-discriminative component and an emotional-affective component. The great progress in the genetic, molecular, cellular and systemic levels on the study of the sensory dimension of pain has been made. However, the study of the emotional components of pain is relatively backward. A line of clinic observations indicates that chronic pain and pain-related negative emotion affect the physical and mental health of patients. This review summarizes the main progress from our and other laboratories regarding the affective component of pain, elaborates the neuronal mechanisms of pain-related aversive emotion in the anterior cingulate cortex (ACC), especially the critical role of NMDA receptors and ERK-CREB pathway. A variety of regulatory molecules, such as synapse associated protein SIP30 and estrogen contribute to pain-related aversive emotion via facilitating presynaptic glutamate release and postsynaptic NMDA receptor-mediated synaptic transmission. The far-reaching effects of pain-related negative emotion on patients with chronic pain are emphasized.