Challenging the catechism of therapeutics for chronic neuropathic pain: Targeting CaV2.2 interactions with CRMP2 peptides

Polina Feldman, Rajesh Khanna

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations

Abstract

Chronic neuropathic pain management is a worldwide concern. Pharmaceutical companies globally have historically targeted ion channels as the therapeutic catechism with many blockbuster successes. Remarkably, no new pain therapeutic has been approved by European or American regulatory agencies over the last decade. This article will provide an overview of an alternative approach to ion channel drug discovery: targeting regulators of ion channels, specifically focusing on voltage-gated calcium channels. We will highlight the discovery of an anti-nociceptive peptide derived from a novel calcium channel interacting partner - the collapsin response mediator protein 2 (CRMP2). In vivo administration of this peptide reduces pain behavior in a number of models of neuropathic pain without affecting sympathetic-associated cardiovascular activity, memory retrieval, sensorimotor function, or depression. A CRMP2-derived peptide analgesic, with restricted access to the CNS, represents a completely novel approach to the treatment of severe pain with an improved safety profile. As peptides now represent one of the fastest growing classes of new drugs, it is expected that peptide targeting of protein interactions within the calcium channel complex may be a paradigm shift in ion channel drug discovery.

Original languageEnglish (US)
Pages (from-to)27-36
Number of pages10
JournalNeuroscience Letters
Volume557
DOIs
StatePublished - Dec 17 2013
Externally publishedYes

Keywords

  • Anti-nociceptive
  • CRMP2
  • Calcium channels
  • Neuropathic pain
  • Peptide

ASJC Scopus subject areas

  • Neuroscience(all)

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