Local anesthetics decrease the excitability of all neurons by blocking voltage-gated sodium channels non-selectively. We have developed a technology to silence only those sensory neurons – the nociceptors – that trigger pain, itch, and cough. I will tell you why and how we devised the strategy, the way we showed that it works, and will also discuss its implications for treating multiple human disorders.

Local anesthetics decrease the excitability of all neurons by blocking voltage-gated sodium channels non-selectively. We have developed a technology to silence only those sensory neurons – the nociceptors – that trigger pain, itch, and cough. I will tell you why and how we devised the strategy, the way we showed that it works, and will also discuss its implications for treating multiple human disorders.

Pain has both a sensory and emotional component and is driven by activation of sensory neurones called nociceptors that are tuned to detect noxious stimuli in a process called nociception. Although nociception functions as a detect and protect mechanism. and is found in many organisms, this system becomes dysregulated in a number of conditions where chronic pain presents as a key symptom, for example osteoarthritis. Nociceptors do not innervate empty space though and do not act alone. Going beyond the neurone, other cell types, such as fibroblast-like synoviocytes interact with and modify the function of nociceptors, which is likely a key contributor to the chronification of pain. In this talk, I will look at how combining pre-clinical mouse work with human tissue and genetics might provide a way to accelerate new analgesics from bench to bedside, giving examples from our work in joint pain, bowel pain and labour pain.