Referenced in: none

Automatically associated channels: Nav1.8

Title: VGLUT2-dependent glutamate release from nociceptors is required to sense pain and suppress itch.

Authors: Yang Liu, Omar Abdel Samad, Ling Zhang, Bo Duan, Qingchun Tong, Claudia Lopes, Ru-Rong Ji, Bradford B Lowell, Qiufu Ma

Journal, date & volume: Neuron, 2010 Nov 4 , 68, 543-56

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21040853

Abstract
Itch can be suppressed by painful stimuli, but the underlying neural basis is unknown. We generated conditional null mice in which vesicular glutamate transporter type 2 (VGLUT2)-dependent synaptic glutamate release from mainly Nav1.8-expressing nociceptors was abolished. These mice showed deficits in pain behaviors, including mechanical pain, heat pain, capsaicin-evoked pain, inflammatory pain, and neuropathic pain. The pain deficits were accompanied by greatly enhanced itching, as suggested by (1) sensitization of both histamine-dependent and histamine-independent itch pathways and (2) development of spontaneous scratching and skin lesions. Strikingly, intradermal capsaicin injection promotes itch responses in these mutant mice, as opposed to pain responses in control littermates. Consequently, coinjection of capsaicin was no longer able to mask itch evoked by pruritogenic compounds. Our studies suggest that synaptic glutamate release from a group of peripheral nociceptors is required to sense pain and suppress itch. Elimination of VGLUT2 in these nociceptors creates a mouse model of chronic neurogenic itch.