Novel Synaptic Mechanisms for Chronic Pain and Anxiety

Glutamate is the primary excitatory transmitter of sensory transmission and perception in the central nervous system. Painful or noxious stimuli 'teach' humans and animals to avoid potentially dangerous objects or environments, whereas tissue injury itself causes unnecessary chronic pain that can even last for long periods of time.  Conventional pain medicines often fail to control chronic pain.  Recent neurobiological studies suggest that synaptic plasticity taking place in sensory pathways, from spinal dorsal horn to cortical areas, contributes to chronic pain.  We have characterized two forms of long-term potentiation (LTP) in the anterior cingulate cortex (ACC); a presynaptic form (pre-LTP) that requires kainate receptors and a postsynaptic form (post-LTP) that requires N-methyl-D-aspartate receptors. Our results demonstrate that cortical LTPs contribute to chronic pain and anxiety; and inhibiting these different forms of LTP may help us to develop novel drugs for the future treatment of chronic pain and anxiety.