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Suppression of pain‐related behavior in two distinct rodent models of peripheral neuropathy by a homopolyarginine‐conjugated CRMP 2 peptide
Author(s) -
Ju Weina,
Li Qi,
Allette Yohance M.,
Ripsch Matthew S.,
White Fletcher A.,
Khanna Rajesh
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12070
Subject(s) - peptide , transient receptor potential channel , nociception , mediator , medicine , sensory system , neuropathic pain , pharmacology , peripheral neuropathy , trpm8 , systemic administration , neuroscience , substance p , depolarization , receptor , chemistry , endocrinology , biology , trpv1 , biochemistry , neuropeptide , in vivo , microbiology and biotechnology , diabetes mellitus
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 ST 1‐104, a short peptide from the collapsin response mediator protein 2 ( CRMP 2), which disrupted the CaV2.2– CRMP 2 interaction and suppressed a model of HIV ‐related neuropathy induced by anti‐retroviral therapy but not traumatic neuropathy. Here, we report ST 2‐104 –a peptide wherein the cell‐penetrating TAT motif has been supplanted with a homopolyarginine motif, which dose‐dependently inhibits the CaV2.2– CRMP 2 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 ST 2‐104 does not affect thermal or tactile nociceptive behavioral changes. Importantly, ST 2‐104 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 ST 2‐104 are discussed.