Piezo2 mediates mechanical sensitivity and injury-induced hypersensitivity in MrgprD-expressing nociceptors

Authors
Jorge Fernández-Trillo, Marina Villaro-Capellán, Elvira de la Peña, Félix Viana, Ana Gomis


Lab

Journal
Pain

Abstract
Piezo2 mediates mechanically activated currents in MrgprD neurons. (A) Representative images of DRG sections after RNAscope in situ hybridization for MrgprD (magenta) and Piezo2 (green) inMrgprD-tdTomato(wild-type; n = 704 cells, 5 DRGs) andMrgprD-tdTomato;Piezo2fl/null(Piezo2KO;n = 1462 cells, 9 DRGs) mice. Scale bar, 100 μm. Arrows indicate double-labeled cells. Histograms summarize the proportion of MrgprD+neurons expressing Piezo2 transcripts. (B) Representative recordings of rapidly adapting (RA; τ = 0.61 ms; 3μm indentation), intermediate adapting (IA; τ = 25 ms; 13 μm indentation) and slowly adapting (SA; τ = 456 ms; 7 μm indentation) currents from cultured DRG neurons fromMrgprD-tdTomatomice using indentation stimulation. (C) Pie charts illustrating the distribution of each current type recorded in β-alanine–positive (n = 31) and β-alanine–negative (n = 16) neurons from 10MrgprD-tdTomatomice (wild-type for Piezo2). (D) Pie charts similar to (C), showing the proportion of each current recorded from 5MrgprD-tdTomato;Piezo2fl/nullmice (β-alanine positive [n = 15]); (β-alanine negative [n = 15]). (E) Representative whole-cell current-clamp recordings illustrating phasic (top), mixed (middle), and tonic (bottom) firing patterns ofMrgprDDRG neurons fromMrgprD-tdTomatomice. (F) Top, representative MrgprD+neurons exhibiting a long-duration action potential with a pronounced inflexion during the repolarization phase (hump) as evidenced by the differentiated trace showing a second negative peak (lower trace). Bottom, similar representation from a MrgprD+neuron exhibiting a narrow action potential without an inflection and lacking a second delayed negative peak. (G) Proportion of each firing pattern in β-alanine–positive and β-alanine–negative neurons in Piezo2 WT and Piezo2KO mice. (Piezo2 WT β-alanine+n = 31 and β-alanine-n = 15, 10 mice. Piezo2KO β-alanine+n = 15 y β-alanine-n = 13, 5 mice).

Keywords/Topics
mechanical sensitivity; mechanically activated currents; frommrgprd-tdtomatomice; 10mrgprd-tdtomatomice wild-type; 5mrgprd-tdtomato piezo2fl nullmice; mice; piezo2; injury-induced hypersensitivity; -expressing nociceptors; piezo2 mediates

Source :

https://pmc.ncbi.nlm.nih.gov/articles/PMC13225245/

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