The Young Life Scientist’ Symposium at King’s College in London on October 4 was well executed and informative. Entitled Current Progress on the Physiology & Pharmacology of TRP Channels, a wide array of human disorders that could invoke TRP channels, and therapies invoking the same, were discussed.
Dr. David Anderson (King’s College) kicked off the lectures with the remarkable discovery that TRPA1 ion channels form the principal mechanism of action acetaminophen, the widely used analgesic and antipyretic whose mechanism of action has incredibly remained unclear despite its popularity for the last 50 years. He presented data showing that the acetaminophen metabolite NAPQI is a potent TRPA1 agonist, and is formed in the mouse spinal cord following administration of paracetamol. Moreover, the anti-nociceptive effects of systemic and spinal administration are lost in TRPA1 -/- mice. His research is providing molecular mechanisms for the benefits of acetaminophen, and points to spinal TRPA1 activation as a pharmacological strategy for pain relief.
D. Elena Wilde (King’s College) presented data regarding TRP-channel agonist-induced cough in guinea pigs. Though cough is a protective respiratory reflex, it can become pathogenic and is a common reason patients seek medical attention.
Dr. Peter Cox from Pfizer Neusentis presented very interesting data about the development of a TRPA1 agonist for the treatment of itching. His lecture included elucidation the molecular neurobiology of itch sensory processing, and how TRPA1 may be a potential target for the treatment of chronic itch conditions such as atopic dermatitis.
Dr. Manish Madasu (National University of Ireland) was awarded 1st Prize in the poster competition. Dr. Madasu presented data discussing the differential display of pain sensitivity in Sprague-Dawley (SD) and Wistar-Kyoto (WK) rats. WK rats exhibit a more hyperalgesic phenotype than do SD in response to intra-plantar formalin administration. TRPV1 mRNA levels were higher in the lateral periaqueductal grey (LPAG) of WK compared to SD rats. Pharmacological blockade of TRPV1 in the LPAG resulted in discrete and transient reductions in pain behavior in SD but not WK rats. Taken together, the data indicate a role of TRPV1 in the different nociceptive behavior between strains.
Professor Susan Brain, Head of the Department of Pharmacology at King’s College, provided the keynote presentation. She elegantly dovetailed her productive contributions to the activities of calcitonin gene-related peptide (CGRP) to the activation of TRPV1 and TRPA1. She has shown, for example, that addition of a TRPV1 agonist such as capsaicin, or a TRPA1 agonist such as cinnamaldehyde, leads to CGRP-dependent increased blood flow in skin (1).
She also presented new data that demonstrate that upregulation of αCGRP in hypertension may be protective against vascular hypertrophy, fibrosis, and oxidative stress (2).
My favorite presentation was by Dr. Julie Keeble (King’s College), an active scientist with a published track record of TRP research in high-impact journals. It was her lively entertaining presentation about her work with Mission Discovery, a program that enables school children to send experiments to space, rather that was alluring. Her enthusiasm for her leadership role in Space educational initiatives was palpable. She shared with the audience details about the types of experiments designed by the students, the trials and tribulations of launch, the care and consideration of the experiments by the astronauts, and their findings.
Coincidentally, while in London, it was interesting to learn about a NASA-funded study on the use of therapeutic hibernation to aid in transporting humans to Mars. CNN Report: Sleeper spaceship could carry first humans to Mars in hibernation state The company SpaceWorks Engineering, based in Atlanta, GA, proposes the design of a torpor-inducing transfer habitat to the red planet. CNN reported that SpaceWorks “found a Chinese medical study in which trauma patients stayed in torpor for longer periods”, up to 14 days in some cases. Subjects “in torpor” for ~ two weeks fared as well as those “hibernating” for shorter durations. [Note: If anyone can point me to the actual publication, I’d be very interested in reading it – email me at Hampton@mousespecifics.com].
SpaceWorks would have enjoyed Dr. Heather Wilson’s (from Dr. Keeble’s lab!) presentation on the effects of exogenous hydrogen sulfide on body temperature in mice. Inhaled H2S in young mice show dose-dependent hypothermia and hypo-metabolism, effects that were blunted in TRPA1 -/- mice. Her research provides novel in vivo evidence that H2S-induced hypothermia and hypo-metabolism are at least partially TRPA1-mediated.
Many thanks to the organizing committee, with a special shout out to Aisah Aubdool and Khadija Alawi for getting Mouse Specifics, Inc. involved in their outstanding event. Cheers!
- Russell et al. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev 2014 94 in press.
- Smillie et al. An ongoing role of α-calcitonin gene-related peptide as part of a protective network against hypertension, vascular hypertrophy, and oxidative stress. Hypertension. 2014 63:1056-62.
- CNN Report: Sleeper spaceship could carry first humans to Mars in hibernation state