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

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 Ca(2+) influx in sensory neurons. Ca(2+) 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.

• Authors: Weina Ju, Qi Li, Yohance M Allette, Matthew S Ripsch, Fletcher A White, Rajesh Khanna
• Journal: Journal of neurochemistry (J Neurochem) Vol. 124 Issue 6 Pg. 869-79 (Mar 2013) ISSN: 1471-4159 [Electronic] England
• PMID: 23106100 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 International Society for Neurochemistry.

Chemical References

• Intercellular Signaling Peptides and Proteins
• Nerve Tissue Proteins
• Peptides
• collapsin response mediator protein-2
• polyarginine

Topics

• Amino Acid Sequence
• Animals
• Cells, Cultured
• Disease Models, Animal
• Female
• Intercellular Signaling Peptides and Proteins
• Mice
• Molecular Sequence Data
• Nerve Tissue Proteins (genetics, therapeutic use)
• Pain (drug therapy, pathology, psychology)
• Pain Management (methods)
• Peptides (genetics, therapeutic use)
• Peripheral Nervous System Diseases (drug therapy, pathology, psychology)
• Rats
• Rats, Sprague-Dawley