Neuronal TRPV4 Channel as a Mechanosensor in Itch
(2024) Belgian Society of Physiology and Pharmacology meeting — Location: Brussels (29.November.2024)
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- Abstract
- Acute and chronic itch (pruritus) are distinct clinical phenomena, although both involve the activation of sensory neurons and the central nervous system. Acute itch is typically a transient response to external stimuli, such as insect bites, allergic reactions or skin irritants, and usually resolves when the offending factor is removed or treated. In contrast, chronic pruritus persists for longer periods, often more than six weeks, and is often associated with underlying medical conditions such as eczema, atopic dermatitits or systemic diseases such as liver or kidney failure. Although the mechanisms underlying both acute and chronic itch are still being investigated, they involve complex interactions between peripheral sensory neurons, immune cells and central nervous pathways. The TRPV4 ion channel is a receptor known for its involvement in pain perception, temperature regulation and mechanosensation. Despite significant advances in understanding the role of TRPV4 in various physiological and pathophysiological processes, its contribution to itch remains largely unexplored. Recent evidence suggests that TRPV4 may be involved in the modulation of itch sensation, but its precise function and the mechanism by which it contributes to itch pathways remain unclear. Using Ca2+ imaging with genetically encoded indicator GCaMP and in situ hybridisation, we found that TRPV4 is expressed in trigeminal sensory neurons co-expressing Neurofilament 200 (NF200), a marker of mechanoreceptors. Conditional knockout (KO) of TRPV4 in sensory neurons significantly altered scratching behaviour in both acute (histamine-induced) and chronic (atopic dermatitis) itch models. Specifically, loss of TRPV4 function in trigeminal neurons profoundly affected both mechanical itch and itch sensitization. These findings highlight a novel role for TRPV4 in the mechanosensation of itch and offer promising prospects for the development of therapies for both acute and chronic pruritus.
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Bourgy, C., Parpaite, T., Barbeau, S., Yerna, X., Azmani Matar, K., Lambermont, I., Schakman, O., Gailly, P., & Gualdani, R. (2024). Neuronal TRPV4 Channel as a Mechanosensor in Itch. Belgian Society of Physiology and Pharmacology meeting, Brussels. https://hdl.handle.net/2078.5/238344