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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Liu, Y; Abdel Samad, O; Zhang, L; Duan, B; Tong, Q; Lopes, C; Ji, R-R; Lowell, BB; Ma, Q

Published Date

  • November 4, 2010

Published In

Volume / Issue

  • 68 / 3

Start / End Page

  • 543 - 556

PubMed ID

  • 21040853

Pubmed Central ID

  • 21040853

Electronic International Standard Serial Number (EISSN)

  • 1097-4199

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2010.09.008

Language

  • eng

Conference Location

  • United States