New research published online December 31 in Neuron posits that a novel form of synaptic plasticity in the anterior cingulate cortex (ACC) may account for anxiety disorders that are often associated with chronic pain. The ACC plays a critical role in chronic pain, and human studies suggest that it might be a hub for anxiety as well. In people with chronic pain, anxiety levels predict the extent of pain, and in imaging studies, people with anxiety show increased activation in the ACC.
Previous work by the research team from the University of Toronto found that changes in synaptic strength in the ACC contribute to the emergence of neuropathic pain, through a form of long-term potentiation (LTP), in which AMPA-type glutamate receptors are increased on the postsynaptic membrane. In this study, the team identified a different kind of LTP, generated by increased glutamate release from presynaptic terminals onto pyramidal neurons of the ACC. Their results show that this presynaptic LTP (pre-LTP) is induced after nerve injury or inflammation, and contributes not only to pain, but also to anxiety in a mouse model of neuropathic pain. The findings suggest new potential avenues for therapeutic development that involve preventing pre-LTP buildup in the ACC.
Read a news story about the research, with link to the journal article, here.