Canadian Association of Neuroscience Review: Cellular and synaptic insights into physiological and pathological pain - EJLB-CIHR Michael Smith Chair in Neurosciences and Mental Health Lecture

Neurons and synapses in the central nervous system are plastic, undergoing long-term changes throughout life. Studies of molecular and cellular mechanisms of such changes not only provide important insight into how we learn and store new knowledge in our brains, but they also reveal the mechanisms of pathological changes that occur following injury. The author proposes that during induction, neuronal mechanisms underlying physiological functions, such as learning and memory, may share some common signaling molecules with abnormal or injury-related changes in the brain. Distinct synaptic and neuronal network mechanisms are involved in pathological pain as compared to cognitive learning and memory. Nociceptive information is transmitted and regulated at different levels of the brain, from the spinal cord to the forebrain. Furthermore, N-methyl-D-aspartate receptor-dependent and calcium-calmodulin activated adenylyl cyclases (AC1 and AC8) in the anterior cingulate cortex play important roles in the induction and expression of persistent inflammatory and neuropathic pain. Neuronal activity in the anterior cingulate cortex can also influence nociceptive transmission in the dorsal horn of the spinal cord by activating the endogenous facilitatory system. Our results provide important synaptic and molecular insights into physiological responses to injury.