Next Article in Journal
Immunotherapy for Prostate Cancer: Where We Are Headed
Next Article in Special Issue
Sulfuretin Attenuates MPP+-Induced Neurotoxicity through Akt/GSK3β and ERK Signaling Pathways
Previous Article in Journal
The Imbalance between n-6/n-3 Polyunsaturated Fatty Acids and Inflammatory Bowel Disease: A Comprehensive Review and Future Therapeutic Perspectives
Previous Article in Special Issue
Diffuse Axonal Injury and Oxidative Stress: A Comprehensive Review
Article Menu
Issue 12 (December) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(12), 2626; https://doi.org/10.3390/ijms18122626

Duloxetine Protects against Oxaliplatin-Induced Neuropathic Pain and Spinal Neuron Hyperexcitability in Rodents

1
Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea
2
Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea
3
Department of Neurosurgery, College of Medicine, Kyung Hee University, Kyung Hee University Hospital, Seoul 02447, Korea
4
Yeongju Municipal Hospital, Yeongju-si 36051, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 16 October 2017 / Revised: 28 November 2017 / Accepted: 30 November 2017 / Published: 5 December 2017
(This article belongs to the Special Issue Neuroprotective Strategies 2017)
Full-Text   |   PDF [1881 KB, uploaded 6 December 2017]   |  

Abstract

Oxaliplatin is a widely used chemotherapy agent, but induces serious peripheral neuropathy. Duloxetine is a dual reuptake inhibitor of serotonin and norepinephrine, and is shown to be effective against pain. However, whether and how duloxetine can attenuate oxaliplatin-induced allodynia in rodents is not clearly understood. A single injection of oxaliplatin (6 mg/kg, intraperitoneal; i.p.) induced a cold and mechanical allodynia, which was assessed by acetone and von Frey filament tests, respectively. When significant allodynic signs were observed, three different doses of duloxetine (10, 30, and 60 mg/kg, i.p.) were injected. Administration of 30 and 60 mg/kg of duloxetine significantly reduced the allodynia, whereas 10 mg/kg did not. By using an in vivo extracellular recording method, we further confirmed that 30 mg/kg of duloxetine could significantly inhibit the hyperexcitability of spinal wide dynamic range (WDR) cells. The anti-allodynic effect of duloxetine was completely blocked by an intrathecal injection of phentolamine (non-selective α-adrenergic receptor antagonist, 20 μg), or prazosin (α1-adrenergic receptor antagonists, 10 μg); however, idazoxan (α2-adrenergic receptor antagonist, 10 μg) did not block it. In conclusion, we suggest that duloxetine may have an effective protective action against oxaliplatin-induced neuropathic pain and spinal hyperexcitability, which is mediated by spinal α1-adrenergic receptors. View Full-Text
Keywords: chemotherapy-induced peripheral neuropathy; duloxetine; noradrenergic receptor; oxaliplatin; wide dynamic range (WDR) cell chemotherapy-induced peripheral neuropathy; duloxetine; noradrenergic receptor; oxaliplatin; wide dynamic range (WDR) cell
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Kim, W.; Chung, Y.; Choi, S.; Min, B.-I.; Kim, S.K. Duloxetine Protects against Oxaliplatin-Induced Neuropathic Pain and Spinal Neuron Hyperexcitability in Rodents. Int. J. Mol. Sci. 2017, 18, 2626.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top