A subpopulation of nociceptors specifically linked to itch

Abstract

Itch-specific neurons have been sought for decades. The existence of such neurons is in doubt recently due to the observation that itch-mediating neurons also respond to painful stimuli. Here, we genetically labeled and manipulated MrgprA3+ neurons in dorsal root ganglion (DRG) and found that they exclusively innervate the epidermis of the skin and respond to multiple pruritogens. Ablation of MrgprA3+ neurons led to significant reductions in scratching evoked by multiple pruritogens and occurring spontaneously under chronic itch conditions whereas pain sensitivity remained intact. Importantly, mice with TRPV1 exclusively expressed in MrgprA3+ neurons exhibited only itch- and not pain behavior in response to capsaicin. Although MrgprA3+ neurons are sensitive to noxious heat, activation of TRPV1 in these neurons by noxious heat did not alter pain behavior. These data suggest that MrgprA3 defines a specific subpopulation of DRG neurons mediating itch. Our study opens new avenues for studying itch and developing anti-pruritic therapies.

An Update on Peripheral Mechanisms and Treatments of Itch

“…49,50) A more recent study using conditional transgenic mice revealed that ablation of MrgprA3 + drG neurons led to substantial reductions in scratching evoked by multiple pruritogens and occurring spontaneously under chronic itch conditions. 51) However, pain sensitivity remained intact in these mice. Moreover, mice in which transient receptor potential vanilloid 1 (trPV1) was exclusively expressed in MrgprA3 + DRG neurons exhibited itch, but not pain, behavior in response to capsaicin.…”

Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey

“…However, overall TRPV1 expression in the central nervous system (CNS) is considerably lower than in the DRG (Cavanaugh et al, 2011;Han et al, 2012;Sanchez et al, 2001;Szabo et al, 2002). Indeed, some studies have failed to detect the presence of TRPV1 in the CNS (Benninger et al, 2008;Caterina et al, 2000;Szallasi, 1995;Tominaga et al, 1998) possibly due to complexity in genes and strain-related variations (Sanchez et al, 2001;Sudbury et al, 2010).…”

Selective Manipulation of Neural Circuits

“…One gene is expressed in a genetically defined set of neurons. Another gene codes for the neurotoxin that kills the cells with a known genetic identity [166][167][168]. Saporin, a toxin protein from a plant Saponara officinalis, can also be used for cell type or circuit-specific ablation.…”