Neurobiology of chronic pain – mechanisms, management, and in-between
Time: 15:00 – 16:00
Chronic pain is defined as pain experienced for a period of six months or longer and there are currently 28 million people in the UK that live with pain. NaV1.7 is a key ion channel in pain signaling. Gain-of-function mutations in the human NaV1.7 gene produce sensory neurons hyperexcitability associated with severe pain; whereas loss-of-function mutations generate congenital insensibility to pain syndromes. Efforts to develop NaV1.7 inhibitors for pain therapeutics have consistently failed.
Post-translational modifications of NaVs and/or auxiliary sub-units and protein-protein interactions have been reported as NaV-trafficking mechanisms. It was recently identified that modification of the axonal collapsin response mediator protein 2 (CRMP2) by a small ubiquitin-like modifier (SUMO) controls both trafficking and currents of NaV1.7.
Speakers at this webinar will present an innovative approach of focusing on a unique mechanism of action of compounds that involve an indirect targeting to control surface expression and activity of the NaV1.7 channel. At this event, you will hear how researchers are capitalizing on this unique pathway for NaV1.7 regulation and have identified compounds designed to inhibit enzyme interactions to block relevant proteins. Over 266 compounds have been identified in this manner and these presentations will explore some of the results where there has been inhibition of interactions, anti-allodynic activities without loss of motoric performance or sympathetic side effects. Animal pharmacological studies have also indicated where some of the compounds displayed extended duration of action compared with morphine upon intrathecal administration to rats. Additional studies demonstrated inhibition of NaV1.7 currents in human and porcine sensory neurons, thus increasing likelihood of translational success and ‘de-risking’ compound selection.
We are pleased to welcome Dr Eilís Dowd, Lecturer in Pharmacology at National University of Ireland, Galway, and Neuronal Signaling journal Associate Editor, as chair of this webinar, along with speakers, Professor Rajesh Khanna who will discuss channeling chronic pain, and Professor David Finn who will speak on pain and negative affect.
- Professor Rajesh Khanna, Professor of Pharmacology at the University of Arizona College of Medicine. Neuronal Signaling journal Associate Editor
- Professor David Finn, Professor and Head of Pharmacology and Therapeutics, Principal Investigator, Co-Founder and Co-Director of the Centre for Pain Research at the National University of Ireland, Galway.