Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury.

Abstract:

:Neuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to neuropathic pain, the molecular and cellular mechanisms underlying this disinhibition are unclear. Here, we combined pharmacogenetic activation and selective ablation approaches in mice to define the contribution of spinal cord parvalbumin (PV)-expressing inhibitory interneurons in naive and neuropathic pain conditions. Ablating PV neurons in naive mice produce neuropathic pain-like mechanical allodynia via disinhibition of PKCγ excitatory interneurons. Conversely, activating PV neurons in nerve-injured mice alleviates mechanical hypersensitivity. These findings indicate that PV interneurons are modality-specific filters that gate mechanical but not thermal inputs to the dorsal horn and that increasing PV interneuron activity can ameliorate the mechanical hypersensitivity that develops following nerve injury.

journal_name

Cell Rep

journal_title

Cell reports

authors

Petitjean H,Pawlowski SA,Fraine SL,Sharif B,Hamad D,Fatima T,Berg J,Brown CM,Jan LY,Ribeiro-da-Silva A,Braz JM,Basbaum AI,Sharif-Naeini R

doi

10.1016/j.celrep.2015.09.080

subject

Has Abstract

pub_date

2015-11-10 00:00:00

pages

1246-1257

issue

6

issn

2211-1247

pii

S2211-1247(15)01134-1

journal_volume

13

pub_type

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