title: Modeling nociception in zebrafish: a way forward for unbiased analgesic discovery.
abstract: Acute and chronic pain conditions are often debilitating, inflicting severe physiological, emotional and economic costs and affect a large percentage of the global population. However, the development of therapeutic analgesic agents based primarily on targeted drug development has been largely ineffective. An alternative approach to analgesic development would be to develop low cost, high throughput, untargeted animal based behavioral screens that model complex nociceptive behaviors in which to screen for analgesic compounds. Here we describe the development of a behavioral based assay in zebrafish larvae that is effective in identifying small molecule compounds with analgesic properties. In a place aversion assay, which likely utilizes supraspinal neuronal circuitry, individually arrayed zebrafish larvae show temperature-dependent aversion to increasing and decreasing temperatures deviating from rearing temperature. Modeling thermal hyperalgesia, the addition of the noxious inflammatory compound and TRPA1 agonist allyl isothiocyanate sensitized heat aversion and reversed cool aversion leading larvae to avoid rearing temperature in favor of otherwise acutely aversive cooler temperatures. We show that small molecules with known analgesic properties are able to inhibit acute and/or sensitized temperature aversion.
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, Washington, 98195, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Curtright
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, Washington, 98195, United States of America.
authors.forename: Micaela
authors.initials: M
authors.lastname: Rosser
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, Washington, 98195, United States of America.
authors.forename: Shamii
authors.initials: S
authors.lastname: Goh
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, Washington, 98195, United States of America.
authors.forename: Bailey
authors.initials: B
authors.lastname: Keown
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, Washington, 98195, United States of America.
authors.forename: Erinn
authors.initials: E
authors.lastname: Wagner
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, Washington, 98195, United States of America.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Sharifi
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, Washington, 98195, United States of America; Neurobiology and Behavior Graduate Program, University of Washington, Seattle, Washington, 98195, United States of America.
authors.forename: David W
authors.initials: DW
authors.lastname: Raible
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, Washington, 98195, United States of America; Neurobiology and Behavior Graduate Program, University of Washington, Seattle, Washington, 98195, United States of America.
authors.forename: Ajay
authors.initials: A
authors.lastname: Dhaka
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy / Q000503:physiopathology; D055808:Drug Discovery / Q000379:methods; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D017879:Isothiocyanates / Q000494:pharmacology; D007814:Larva / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D059225:Nociception / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000494:pharmacology; D013696:Temperature; D050051:Transient Receptor Potential Channels / Q000819:agonists; D015027:Zebrafish / Q000378:metabolism / Q000502:physiology*
chemical_list: D000700:Analgesics; D017879:Isothiocyanates; D054852:Small Molecule Libraries; D050051:Transient Receptor Potential Channels; C004471:allyl isothiocyanate