Suppression of pain-related behavior in two distinct rodent models of peripheral neuropathy by a homopolyarginine-conjugated CRMP2 peptide

Weina Ju, Qi Li, Yohance M. Allette, Matthew S. Ripsch, Fletcher A. White, Rajesh Khanna

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The N-type voltage-gated calcium channel (CaV2.2) is a clinically endorsed target in chronic pain treatments. As directly targeting the channel can lead to multiple adverse side effects, targeting modulators of CaV2.2 may prove better. We previously identified ST1-104, a short peptide from the collapsin response mediator protein 2 (CRMP2), which disrupted the CaV2.2-CRMP2 interaction and suppressed a model of HIV-related neuropathy induced by anti-retroviral therapy but not traumatic neuropathy. Here, we report ST2-104 -a peptide wherein the cell-penetrating TAT motif has been supplanted with a homopolyarginine motif, which dose-dependently inhibits the CaV2.2-CRMP2 interaction and inhibits depolarization-evoked Ca2+ influx in sensory neurons. Ca2+ influx via activation of vanilloid receptors is not affected by either peptide. Systemic administration of ST2-104 does not affect thermal or tactile nociceptive behavioral changes. Importantly, ST2-104 transiently reduces persistent mechanical hypersensitivity induced by systemic administration of the anti-retroviral drug 2′,3′-dideoxycytidine (ddC) and following tibial nerve injury (TNI). Possible mechanistic explanations for the broader efficacy of ST2-104 are discussed. Chronic neuropathic pain remains a worldwide medical problem with few effective therapies. Drugs targeting calcium channels are in clinical use as first-line treatments for alleviation of neuropathic pain. However, targeting these channels can lead to serious complications. Here, we report that a peptide derived from CRMP2 - a modulator of calcium channels, offers problem-free pain relief in rodent models of neuropathic pain.

Original languageEnglish (US)
Pages (from-to)869-879
Number of pages11
JournalJournal of Neurochemistry
Volume124
Issue number6
DOIs
StatePublished - Mar 1 2013

Keywords

  • calcium imaging
  • CaV2.2
  • CRMP2
  • neuropathic pain
  • peptide inhibitor
  • polyarginine motif

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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