PubMed 23774285

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPA , TRPA1

Title: A TRPA1 antagonist reverts oxaliplatin-induced neuropathic pain.

Authors: Cristina Nativi, Roberta Gualdani, Elisa Dragoni, Lorenzo Di Cesare Mannelli, Silvia Sostegni, Martina Norcini, Gabriele Gabrielli, Giancarlo la Marca, Barbara Richichi, Oscar Francesconi, Maria Rosa Moncelli, Carla Ghelardini, Stefano Roelens

Journal, date & volume: Sci Rep, 2013 , 3, 2005

PubMed link:

Neuropathic pain (NeP) is generally considered an intractable problem, which becomes compelling in clinical practice when caused by highly effective chemotherapeutics, such as in the treatment of cancer with oxaliplatin (OXA) and related drugs. In the present work we describe a structurally new compound, ADM_09, which proved to effectively revert OXA-induced NeP in vivo in rats without eliciting the commonly observed negative side-effects. ADM_09 does not modify normal behavior in rats, does not show any toxicity toward astrocyte cell cultures, nor any significant cardiotoxicity. Patch-clamp recordings demonstrated that ADM_09 is an effective antagonist of the nociceptive sensor channel TRPA1, which persistently blocks mouse as well as human variants of TRPA1. A dual-binding mode of action has been proposed for ADM_09, in which a synergic combination of calcium-mediated binding of the carnosine residue and disulphide-bridge-forming of the lipoic acid residue accounts for the observed persistent blocking activity toward the TRPA1 channel.