Cl- channel is required for CXCL10-induced neuronal activation and itch response in a murine model of allergic contact dermatitis

Abstract

Persistent itch often accompanies allergic contact dermatitis (ACD), but the underlying mechanisms remain largely unexplored. We previously demonstrated that CXCL10/ CXCR3 signaling activated a subpopulation of cutaneous primary sensory neurons and mediated itch response after contact hypersensitivity (CHS), a murine model of ACD, induced by squaric acid dibutylester. The purpose of this study was to determine the ionic mechanisms underlying CXCL10-induced neuronal activation and allergic itch. In whole-cell recordings, CXCL10 triggered a current in dorsal root ganglion (DRG) neurons innervating the area of CHS. This current was modulated by intracellular Cl- and blocked by the general Cl- channel inhibitors. Moreover, increasing Ca2+ buffering capacity reduced this current. In addition, blockade of Cl- channels significantly suppressed CXCL10-induced Ca2+ response. In behavioral tests, injection of CXCL10 into CHS site exacerbated itch-related scratching behaviors. Moreover, the potentiating behavioral effects of CXCL10 were attenuated by either of two Cl- channel blockers. Thus, we suggest that the Cl- channel acts as a downstream target mediating the excitatory and pruritic behavioral effects of CXCL10. Cl- channels may provide a promising therapeutic target for the treatment of allergic itch in which CXCL10/CXCR3 signaling may participate.
jn.00187.2017.fulljn.00187.2017.full