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Original Article

The Korean Journal of Pain 2020; 33(1): 30-39

Published online January 1, 2020 https://doi.org/10.3344/kjp.2020.33.1.30

Copyright © The Korean Pain Society.

Gabexate mesilate ameliorates the neuropathic pain in a rat model by inhibition of proinflammatory cytokines and nitric oxide pathway via suppression of nuclear factor-κB

Seon Hee Oh1,* , Hyun Young Lee2,3,* , Young Joon Ki2 , Sang Hun Kim2,3 , Kyung Joon Lim2,3 , and Ki Tae Jung2,3

1School of Medicine, Chosun University, Gwangju, Korea
2Department of Anesthesiology and Pain Medicine, Chosun University Hospital, Gwangju, Korea
3Department of Anesthesiology and Pain Medicine, School of Medicine, Chosun University, Gwangju, Korea

Correspondence to:Ki Tae Jung
Department of Anesthesiology and Pain Medicine, Chosun University Hospital, 365 Pilmun-daero, Dong-gu, Gwangju 61453, Korea
Tel: +82-62-220-3223
Fax: +82-62-223-2333
E-mail: mdmole@chosun.ac.kr

*These authors are co-first authors and contributed equally to this work.

Received: August 23, 2019; Revised: November 2, 2019; Accepted: November 3, 2019

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

This study examined the effects of gabexate mesilate on spinal nerve ligation (SNL)-induced neuropathic pain. To confirm the involvement of gabexate mesilate on neuroinflammation, we focused on the activation of nuclear factor-κB (NF-κB) and consequent the expression of proinflammatory cytokines and inducible nitric oxide synthase (iNOS).

Methods

Male Sprague-Dawley rats were used for the study. After randomization into three groups: the sham-operation group, vehicle-treated group (administered normal saline as a control), and the gabexate group (administered gabexate mesilate 20 mg/kg), SNL was performed. At the 3rd day, mechanical allodynia was confirmed using von Frey filaments, and drugs were administered intraperitoneally daily according to the group. The paw withdrawal threshold (PWT) was examined on the 3rd, 7th, and 14th day. The expressions of p65 subunit of NF-κB, interleukin (IL)-1, IL-6, tumor necrosis factor-α, and iNOS were evaluated on the 7th and 14th day following SNL.

Results

The PWT was significantly higher in the gabexate group compared with the vehicle-treated group (P < 0.05). The expressions of p65, proinflammatory cytokines, and iNOS significantly decreased in the gabexate group compared with the vehicle-treated group (P < 0.05) on the 7th day. On the 14th day, the expressions of p65 and iNOS showed lower levels, but those of the proinflammatory cytokines showed no significant differences.

Conclusions

Gabexate mesilate increased PWT after SNL and attenuate the progress of mechanical allodynia. These results seem to be involved with the anti-inflammatory effect of gabexate mesilate via inhibition of NF-κB, proinflammatory cytokines, and nitric oxide.

Keywords: Analgesia, Gabexate, Hyperalgesia, Human, Inflammation, Neuralgia, NF-Kappa B, Nitric Oxide Synthase Type II, Spinal Nerves