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Experimental Research Article

Korean J Pain 2021; 34(4): 405-416

Published online October 1, 2021 https://doi.org/10.3344/kjp.2021.34.4.405

Copyright © The Korean Pain Society.

Sec-O-glucosylhamaudol mitigates inflammatory processes and autophagy via p38/JNK MAPK signaling in a rat neuropathic pain model

Seon Hee Oh1 , Suk Whee Kim2 , Dong Joon Kim2,3 , Sang Hun Kim2,3 , Kyung Joon Lim2,3 , Kichang Lee4 , 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
4Cardiovascular Reseach Center, Massachusetts General Hospital, Boston, MA, USA

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

Handling Editor: Jong Yeon Park

Received: June 14, 2021; Revised: July 20, 2021; Accepted: July 20, 2021

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 investigated the effect of intrathecal Sec-O-glucosylhamaudol (SOG) on the p38/c-Jun N-terminal kinase (JNK) signaling pathways, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related inflammatory responses, and autophagy in a spinal nerve ligation (SNL)-induced neuropathic pain model.
Methods: The continuous administration of intrathecal SOG via an osmotic pump was performed on male Sprague–Dawley rats (n = 50) with SNL-induced neuropathic pain. Rats were randomized into four groups after the 7th day following SNL and treated for 2 weeks as follows (each n = 10): Group S, sham-operated; Group D, 70% dimethylsulfoxide; Group SOG96, SOG at 96 μg/day; and Group SOG192, SOG at 192 μg/day. The paw withdrawal threshold (PWT) test was performed to assess neuropathic pain. Western blotting of the spinal cord (L5) was performed to measure changes in the expression of signaling pathway components, cytokines, and autophagy. Additional studies with naloxone challenge (n = 10) and cells were carried out to evaluate the potential mechanisms underlying the effects of SOG.
Results: Continuous intrathecal SOG administration increased the PWT with p38/JNK mitogen-activated protein kinase (MAPK) pathway and NF-κB signaling pathway inhibition, which induced a reduction in proinflammatory cytokines with the concomitant downregulation of autophagy.
Conclusions: SOG alleviates mechanical allodynia, and its mechanism is thought to be related to the regulation of p38/JNK MAPK and NF-κB signaling pathways, associated with autophagy during neuroinflammatory processes after SNL.

Keywords: Analgesia, Autophagy, Biological Products, Cytokines, Hyperalgesia, JNK Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Neuralgia, NF-kappa B, Pain.