Grant: Project Grant

Pain caused by injury or disease to the nervous system is called neuropathic pain. The mechanisms underlying neuropathic pain are not well understood and thus, effective therapeutic option for patients with neuropathic pain are lacking. We recently identified a new mechanism through which immune cells in the spinal cord, called microglia, cause pain. We showed that microglia degrade extracellular structures (perineuronal nets (PNNs)) around spinal projection neurons, causing their hyperactivation and pain. Projection neurons are the sole output of pain information from the spinal cord to the brain and therefore, increases in projection neuron activity strongly and specifically promote pain. In the proposed project, we will build on our previous findings to study how microglia modulate PNNs around projection neurons. Importantly, we will use our findings to design strategies to prevent the degradation of PNNs. Together, the proposed research will deepen our understanding of mechanisms underlying the development and maintenance of neuropathic pain, with a potential to facilitate the advent of therapeutic strategies for chronic pain, which is currently both debilitating and difficult to treat.