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Sprague, Jared

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Sprague

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Jared

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Sprague, Jared

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2013 - 20143

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Author's Publications: search.filters.isAuthorOfPublication.3d5b3e93-9fb4-439f-8aaa-92666d29c4e2

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    Photochemical activation of TRPA1 channels in neurons and animals
    (2013) Kokel, David; Cheung, Chung Yan J.; Mills, Robert; Coutinho-Budd, Jaeda; Huang, Liyi; Setola, Vincent; Sprague, Jared; Jin, Shan; Jin, Youngnam N.; Huang, Xi-Ping; Bruni, Giancarlo; Woolf, Clifford; Roth, Bryan L.; Hamblin, Michael; Zylka, Mark J.; Milan, David; Peterson, Randall
    Optogenetics is a powerful research tool because it enables high-resolution optical control of neuronal activity. However, current optogenetic approaches are limited to transgenic systems expressing microbial opsins and other exogenous photoreceptors. Here, we identify optovin, a small molecule that enables repeated photoactivation of motor behaviors in wild type animals. Surprisingly, optovin's behavioral effects are not visually mediated. Rather, photodetection is performed by sensory neurons expressing the cation channel TRPA1. TRPA1 is both necessary and sufficient for the optovin response. Optovin activates human TRPA1 via structure-dependent photochemical reactions with redox-sensitive cysteine residues. In animals with severed spinal cords, optovin treatment enables control of motor activity in the paralyzed extremities by localized illumination. These studies identify a light-based strategy for controlling endogenous TRPA1 receptors in vivo, with potential clinical and research applications in non-transgenic animals, including humans.
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    Activity-dependent silencing reveals functionally distinct itch-generating sensory neurons
    (2013) Roberson, David; Gudes, Sagi; Sprague, Jared; Patoski, Haley A. W.; Robson, Victoria K.; Blasl, Felix; Duan, Bo; Oh, Seog Bae; Bean, Bruce; Ma, Qiufu; Binshtok, Alexander M.; Woolf, Clifford
    The peripheral terminals of primary sensory neurons detect histamine and non-histamine itch-provoking ligands through molecularly distinct transduction mechanisms. It remains unclear, however, whether these distinct pruritogens activate the same or different afferent fibers. We utilized a strategy of reversibly silencing specific subsets of murine pruritogen-sensitive sensory axons by targeted delivery of a charged sodium-channel blocker and found that functional blockade of histamine itch did not affect the itch evoked by chloroquine or SLIGRL-NH2, and vice versa. Notably, blocking itch-generating fibers did not reduce pain-associated behavior. However, silencing TRPV1+ or TRPA1+ neurons allowed AITC or capsaicin respectively to evoke itch, implying that certain peripheral afferents may normally indirectly inhibit algogens from eliciting itch. These findings support the presence of functionally distinct sets of itch-generating neurons and suggest that targeted silencing of activated sensory fibers may represent a clinically useful anti-pruritic therapeutic approach for histaminergic and non-histaminergic pruritus.
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    TRPV1 Sensitization in Primary Sensory Neurons
    (2014-06-06) Sprague, Jared; Woolf, Clifford; Ma, Qiufu; Gaudet, Rachelle; Yellen, Gary
    Pain is a major personal and community burden throughout the world with currently limited treatment options for persistent pain due to unacceptable side effects, dependence or frank inefficacy. It is necessary to understand the anatomical and molecular pathways leading to pain to better cope with the current challenge of treating it.