Physiology Seminar: New roles of microglia and extracellular matrix in pain

Peripheral nerve injury leads to long-lasting pain hypersensitivity. Damaged primary afferents release chemokines, signaling molecules, and proteases to activate spinal cord microglia, which in turn, enhance the excitability of spinal nociceptive circuits. Microglia release an array of bioactive substances that bind to cell surface receptors to increase neuronal activity via modulation of intracellular processes. However, how these substances specifically sensitize pain-processing circuits without affecting other modalities, including itch and proprioception, is not well understood. Studies of mechanisms by which microglia affect neuronal functions in the spinal cord have focused on intracellular mechanisms of action rather than modulation of the extracellular matrix. The extracellular matrix in the central nervous system (CNS) not only provides structural support but is also involved in the regulation of neuronal excitability and synaptic plasticity. Perineuronal nets (PNNs) are the most prominent extracellular matrix structures in the CNS, composed of a proteoglycan core protein decorated by chondroitin sulfate sugar chains. In this talk, I will present evidence showing that PNNs are found around and affect the activity of spinal cord neurons involved in the processing of nociceptive information. I will also describe studies demonstrating the heterogeneity of spinal cord microglia, which exhibit time- and sex-specific transcriptional responses to peripheral nerve injury.

This seminar will take place both in-person and online. Details in attached poster