Our research is focused on revealing the molecular mechanisms that underlie the perception of pain. Sensation of painful stimuli is critical for the survival of the organism. However, acute and chronic pain affects hundreds of millions of people as a result of injury, and is a major symptom in many illnesses. Unfortunately, currently available drug based therapies have numerous deleterious side effects and/or potential for abuse and addiction, while also not being effective in the treatment of persistent pain. Despite great advances, much remains to be understood about how painful or noxious stimuli are perceived and coded by the nervous system. Here we propose to use the zebrafish system to conduct a forward genetic screen to elucidate the fundamental properties of the neural circuits required for the sensation of pain. We have developed specific transgenic tools to examine the development and function of specific neuronal populations that detect modality specific nociceptive stimuli. We propose to use these tools to characterize genetic mutations that alter the behavioral response to heat, cold, mechanical or chemical irritants. Our preliminary data demonstrate that we can identify mutations affecting distinct pain modalities. We expect that this genetic screen will provide a resource for the community interested in the development of neural circuits and the perception of pain, and may provide targets for potential therapies for debilitating painful conditions.

Public Health Relevance

Acute and chronic pain affects hundreds of millions of people, and imposes a severe emotional and economic burden on both individuals and society as a whole, yet much remains unknown about how painful or noxious stimuli are perceived and coded by the nervous system. We propose to use the zebrafish system to identify genes involved in the sensation of painful stimuli and the coordination of resulting behaviors. Identifie genes should help us understand how the neuronal circuits involved in pain perception are assembled, and may provide targets for potential therapies for debilitating painful conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE023730-05
Application #
9281557
Study Section
Special Emphasis Panel (ZRG1-CB-Z (55)R)
Program Officer
Vallejo-Estrada, Yolanda
Project Start
2013-06-05
Project End
2018-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
5
Fiscal Year
2017
Total Cost
$375,945
Indirect Cost
$125,945
Name
University of Washington
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Esancy, Kali; Condon, Logan; Feng, Jing et al. (2018) A zebrafish and mouse model for selective pruritus via direct activation of TRPA1. Elife 7:
Gau, Philia; Curtright, Andrew; Condon, Logan et al. (2017) An ancient neurotrophin receptor code; a single Runx/Cbf? complex determines somatosensory neuron fate specification in zebrafish. PLoS Genet 13:e1006884
Laing, Robyn J; Dhaka, Ajay (2016) ThermoTRPs and Pain. Neuroscientist 22:171-87
Curtright, Andrew; Rosser, Micaela; Goh, Shamii et al. (2015) Modeling nociception in zebrafish: a way forward for unbiased analgesic discovery. PLoS One 10:e0116766