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pISSN 2005-9159
eISSN 2093-0569

Original Article

Korean J Pain 2014; 27(4): 326-333

Published online October 31, 2014 https://doi.org/10.3344/kjp.2014.27.4.326

Copyright © The Korean Pain Society.

Effects of Nefopam on Streptozotocin-Induced Diabetic Neuropathic Pain in Rats

Jae Sik Nam, Yu Seon Cheong, Myong Hwan Karm, Ho Soo Ahn, Ji Hoon Sim, Jin Sun Kim*, Seong Soo Choi*, and Jeong Gil Leem

Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

*Department of Anesthesiology and Pain Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea.

Correspondence to: Seong Soo Choi. Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-1538, Fax: +82-2-470-1363, choiss@amc.seoul.kr

Received: August 22, 2014; Revised: September 19, 2014; Accepted: September 25, 2014

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Nefopam is a centrally acting non-opioid analgesic agent. Its analgesic properties may be related to the inhibitions of monoamine reuptake and the N-methyl-D-aspartate (NMDA) receptor. The antinociceptive effect of nefopam has been shown in animal models of acute and chronic pain and in humans. However, the effect of nefopam on diabetic neuropathic pain is unclear. Therefore, we investigated the preventive effect of nefopam on diabetic neuropathic pain induced by streptozotocin (STZ) in rats.

Methods

Pretreatment with nefopam (30 mg/kg) was performed intraperitoneally 30 min prior to an intraperitoneal injection of STZ (60 mg/kg). Mechanical and cold allodynia were tested before, and 1 to 4 weeks after drug administration. Thermal hyperalgesia was also investigated. In addition, the transient receptor potential ankyrin 1 (TRPA1) and TRP melastatin 8 (TRPM8) expression levels in the dorsal root ganglion (DRG) were evaluated.

Results

Pretreatment with nefopam significantly inhibited STZ-induced mechanical and cold allodynia, but not thermal hyperalgesia. The STZ injection increased TRPM8, but not TRPA1, expression levels in DRG neurons. Pretreatment with nefopam decreased STZ-induced TRPM8 expression levels in the DRG.

Conclusions

These results demonstrate that a nefopam pretreatment has strong antiallodynic effects on STZ-induced diabetic rats, which may be associated with TRPM8 located in the DRG.

Keywords: allodynia, nefopam, painful diabetic neuropathy, streptozotocin, TRPA1, TRPM8