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Open AccessArticle

RgIA4 Accelerates Recovery from Paclitaxel-Induced Neuropathic Pain in Rats

1
School of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USA
2
Center for Excellence in the Neurosciences, University of New England, Biddeford, ME 04005, USA
3
Dept. of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA
4
George E. Whalen Veterans Affairs Medical Center, Salt Lake City, UT 84112, USA
5
Department of Psychiatry, University of Utah, Salt Lake City, UT 84112, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Current address: 257 S 1400 E Room 201, Salt Lake City, UT 84112, USA.
Mar. Drugs 2020, 18(1), 12; https://doi.org/10.3390/md18010012
Received: 27 November 2019 / Revised: 16 December 2019 / Accepted: 18 December 2019 / Published: 21 December 2019
(This article belongs to the Special Issue Ion Channels as Marine Drug Targets)
Chemotherapeutic drugs are widely utilized in the treatment of human cancers. Painful chemotherapy-induced neuropathy is a common, debilitating, and dose-limiting side effect for which there is currently no effective treatment. Previous studies have demonstrated the potential utility of peptides from the marine snail from the genus Conus for the treatment of neuropathic pain. α-Conotoxin RgIA and a potent analog, RgIA4, have previously been shown to prevent the development of neuropathy resulting from the administration of oxaliplatin, a platinum-based antineoplastic drug. Here, we have examined its efficacy against paclitaxel, a chemotherapeutic drug that works by a mechanism of action distinct from that of oxaliplatin. Paclitaxel was administered at 2 mg/kg (intraperitoneally (IP)) every other day for a total of 8 mg/kg. Sprague Dawley rats that were co-administered RgIA4 at 80 µg/kg (subcutaneously (SC)) once daily, five times per week, for three weeks showed significant recovery from mechanical allodynia by day 31. Notably, the therapeutic effects reached significance 12 days after the last administration of RgIA4, which is suggestive of a rescue mechanism. These findings support the effects of RgIA4 in multiple chemotherapeutic models and the investigation of α9α10 nicotinic acetylcholine receptors (nAChRs) as a non-opioid target in the treatment of chronic pain. View Full-Text
Keywords: nicotinic; chemotherapy; paclitaxel; taxane; neuropathic pain; α9α10; conotoxin nicotinic; chemotherapy; paclitaxel; taxane; neuropathic pain; α9α10; conotoxin
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Huynh, P.N.; Giuvelis, D.; Christensen, S.; Tucker, K.L.; McIntosh, J.M. RgIA4 Accelerates Recovery from Paclitaxel-Induced Neuropathic Pain in Rats. Mar. Drugs 2020, 18, 12.

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