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Activity-dependent silencing reveals functionally distinct itch-generating sensory neurons
Roberson, David P,Gudes, Sagi,Sprague, Jared M,Patoski, Haley A W,Robson, Victoria K,Blasl, Felix,Duan, Bo,Oh, Seog Bae,Bean, Bruce P,Ma, Qiufu,Binshtok, Alexander M,Woolf, Clifford J Nature Publishing Group, a division of Macmillan P 2013 NATURE NEUROSCIENCE Vol.16 No.7
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. Using a strategy of reversibly silencing specific subsets of murine pruritogen-sensitive sensory axons by targeted delivery of a charged sodium-channel blocker, we 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<SUP>+</SUP> or TRPA1<SUP>+</SUP> neurons allowed allyl isothiocyanate 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.
Amina El Ayadi,Ron C. Helderman,Celeste C. Finnerty,David N. Herndon,Clifford J. Rosen,Gordon L. Klein 대한골다공증학회 2019 Osteoporosis and Sarcopenia Vol.5 No.3
Objectives: The objective of the study was to determine whether postburn reduction of bone formation occurred earlier than 2e3 weeks after burn injury and whether that reduction was inversely related to marrow adiposity. Methods: Using a rat model of burn injury with sacrifice at 3 days postburn, we measured serum osteocalcin, a biomarker of bone formation, as well as a regulator of glucose metabolism, and counted tibial marrow adipocytes. Results: Serum osteocalcin was reduced as early as 3 days postburn, coinciding with a trend toward decline in marrow adipocyte number rather than demonstrating an inverse relationship with adipocyte count. Conclusions: Factors that may be responsible for the dissociation include lack of circulating sclerostin, previously reported, increased energy demands following burn injury, increased sympathetic tone and perhaps oxidative stress. The relationship between bone formation and marrow adiposity is complex and subject to a variety of influences.