PROJECT: JTC 2025 - Pain: GENUS

Chronic neuropathic pain is extremely difficult to treat with 50-60% of individuals not receiving adequate pain relief from current therapies. The major limitation to effective treatment development is the lack of understanding of the underlying pathophysiology. We will use a clinically relevant, longitudinal, preclinical experimental pipeline to determine the mechanisms driving the development of chronic orofacial neuropathic pain. We aim to track the timing of nerve and brain changes using magnetic resonance imaging and positron emission tomography combined with sensory, behavioural and sleep changes during chronic pain development. We will use electrophysiological, chemo- and optogenetic approaches to map changes in function along the ascending pain pathways at a cellular level and define the neural circuits and synaptic sources of pain-related dysfunction. Given the key role of the endocannabinoid system in modulation and mediation of nociception, affect, sleep and neuroimmune interactions, we will examine alterations in this system in both preclinical models and people with orofacial neuropathic pain. We will use the same methods employed in the preclinical model to assess nerve and brain changes in people with chronic orofacial neuropathic pain. This translational pipeline allows for direct comparisons across and between rats, mice, and humans and provides a platform for mechanistic-based drug discovery.