Edgar Walters

We investigate pain-, injury-, and memory-associated plasticity in species ranging from humans to invertebrates. Our current emphasis is on mechanisms in mammalian nociceptors that are important drivers of persistent pain in diverse pathological conditions, including rodent models of spinal cord injury (SCI) pain, postsurgical and peripheral neuropathic pain, and widespread arthritis pain, as well as collaborative studies on pain-linked mechanisms in human nociceptors. This work builds upon our discovery of chronic spontaneous activity (SA) generated in cell bodies of primary nociceptors in these pain conditions. We developed novel algorithms that revealed critical contributions to hyperactivity from irregular spontaneous depolarizing fluctuations (DSFs) of membrane potential in nociceptors specialized for generating SA in acute and chronic pain conditions, and we are defining the underlying ion channels (including voltage-gated sodium and calcium channels and TRP channels) and cell signaling pathways (including cAMP, ERK, and calcium signaling). We are investigating drugs that suppress large DSF generation, nociceptor hyperactivity, and consequent ongoing pain. These drugs include some approved by the FDA for other purposes and were not expected to have potent ameliorating effects on pain. Our skill sets include diverse electrophysiological methods (whole cell patch, extracellular recording of ongoing and evoked activity in vivo), surgical skills (SCI and related surgeries), cellular and pharmacological methods, and sophisticated behavioral testing approaches (including innovative operant measures of pain and aversion). Our work is unusual in addressing explicit evolutionary questions about the functions and mechanisms of pain.