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Dr Julie Keeble

2014 pump priming award recipient

Dr Julie Keeble, King’s College London

Transient receptor potential vanilloid 1 (TRPV1) is expressed on sensory neurones that mediate pain. It is activated by capsaicin, noxious heat (>42 °C) and low pH (<pH 6.0), amongst other stimuli. It is known that TRPV1 plays a role in painful diseases such as rheumatoid arthritis.

TRPV1 antagonists were recently researched as potential analgesic drugs and were effective in a variety of pain models. However, they were found to cause hyperthermia across species from mice to humans, via a mechanism that is not fully understood. Understanding the mechanism behind the hyperthermia will not only allow the design of better analgesic drugs, but will also provide a greater understanding of the physiology of thermoregulation.

This pump priming award will be used to establish an in vivo method in our laboratory for measuring sympathetic nerve activity in conscious, freely moving animals. We hypothesise that TRPV1 modulates the activity of the sympathetic nervous system to regulate body temperature. Rats will have intra-abdominal telemetry devices implanted to observe changes in the activity of the sympathetic nervous system, following manipulation of the TRPV1 pathway. The results from this study will be used to support data that we have already acquired using other in vivo and in vitro techniques, and form pilot data for a larger grant application in the future.