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http://dx.doi.org/10.3344/kjp.2021.34.4.405

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

Oh, Seon Hee (School of Medicine, Chosun University)
Kim, Suk Whee (Department of Anesthesiology and Pain Medicine, Chosun University Hospital)
Kim, Dong Joon (Department of Anesthesiology and Pain Medicine, Chosun University Hospital)
Kim, Sang Hun (Department of Anesthesiology and Pain Medicine, Chosun University Hospital)
Lim, Kyung Joon (Department of Anesthesiology and Pain Medicine, Chosun University Hospital)
Lee, Kichang (Cardiovascular Reseach Center, Massachusetts General Hospital)
Jung, Ki Tae (Department of Anesthesiology and Pain Medicine, Chosun University Hospital)
Publication Information
The Korean Journal of Pain / v.34, no.4, 2021 , pp. 405-416 More about this Journal
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 ㎍/day; and Group SOG192, SOG at 192 ㎍/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;
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1 Berliocchi L, Maiaru M, Varano GP, Russo R, Corasaniti MT, Bagetta G, et al. Spinal autophagy is differently modulated in distinct mouse models of neuropathic pain. Mol Pain 2015; 11: 3.   DOI
2 Bar-Yosef T, Damri O, Agam G. Dual role of autophagy in diseases of the central nervous system. Front Cell Neurosci 2019; 13: 196.   DOI
3 Ge Y, Huang M, Yao YM. Autophagy and proinflammatory cytokines: interactions and clinical implications. Cytokine Growth Factor Rev 2018; 43: 38-46.   DOI
4 Berliocchi L, Russo R, Maiaru M, Levato A, Bagetta G, Corasaniti MT. Autophagy impairment in a mouse model of neuropathic pain. Mol Pain 2011; 7: 83.
5 Okuyama E, Hasegawa T, Matsushita T, Fujimoto H, Ishibashi M, Yamazaki M. Analgesic components of saposhnikovia root (Saposhnikovia divaricata). Chem Pharm Bull (Tokyo) 2001; 49: 154-60.   DOI
6 Mika J, Zychowska M, Popiolek-Barczyk K, Rojewska E, Przewlocka B. Importance of glial activation in neuropathic pain. Eur J Pharmacol 2013; 716: 106-19.   DOI
7 Uceyler N, Sommer C. Cytokine regulation in animal models of neuropathic pain and in human diseases. Neurosci Lett 2008; 437: 194-8.   DOI
8 Liu G, Xie J, Shi Y, Chen R, Li L, Wang M, et al. Sec-O-glucosylhamaudol suppressed inflammatory reaction induced by LPS in RAW264.7 cells through inhibition of NF-κB and MAPKs signaling. Biosci Rep 2020; 40: BSR20194230.   DOI
9 Kim SH, Jong HS, Yoon MH, Oh SH, Jung KT. Antinociceptive effect of intrathecal sec-O-glucosylhamaudol on the formalin-induced pain in rats. Korean J Pain 2017; 30: 98-103.   DOI
10 Koh GH, Song H, Kim SH, Yoon MH, Lim KJ, Oh SH, et al. Effect of sec-O-glucosylhamaudol on mechanical allodynia in a rat model of postoperative pain. Korean J Pain 2019; 32: 87-96.   DOI
11 Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983; 16: 109-10.   DOI
12 Chung JM, Kim HK, Chung K. Segmental spinal nerve ligation model of neuropathic pain. Methods Mol Med 2004; 99: 35-45.
13 Yaksh TL, Rudy TA. Chronic catheterization of the spinal subarachnoid space. Physiol Behav 1976; 17: 1031-6.   DOI
14 Leung L, Cahill CM. TNF-alpha and neuropathic pain--a review. J Neuroinflammation 2010; 7: 27.   DOI
15 Austin PJ, Moalem-Taylor G. The neuro-immune balance in neuropathic pain: involvement of inflammatory immune cells, immune-like glial cells and cytokines. J Neuroimmunol 2010; 229: 26-50.   DOI
16 Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 1994; 53: 55-63.   DOI
17 Yang CH, Huang HW, Chen KH, Chen YS, Sheen-Chen SM, Lin CR. Antinociceptive potentiation and attenuation of tolerance by intrathecal β-arrestin 2 small interfering RNA in rats. Br J Anaesth 2011; 107: 774-81.   DOI
18 Ko MJ, Lim CY. General considerations for sample size estimation in animal study. Korean J Anesthesiol 2021; 74: 23-9.   DOI
19 Zhuang ZY, Wen YR, Zhang DR, Borsello T, Bonny C, Strichartz GR, et al. A peptide c-Jun N-terminal kinase (JNK) inhibitor blocks mechanical allodynia after spinal nerve ligation: respective roles of JNK activation in primary sensory neurons and spinal astrocytes for neuropathic pain development and maintenance. J Neurosci 2006; 26: 3551-60.   DOI
20 Kim SH, Chung JM. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992; 50: 355-63.   DOI
21 Oh SH, Lee HY, Ki YJ, Kim SH, Lim KJ, Jung KT. 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. Korean J Pain 2020; 33: 30-9.   DOI
22 Chen W, Lu Z. Upregulated TLR3 promotes neuropathic pain by regulating autophagy in rat with L5 spinal nerve ligation model. Neurochem Res 2017; 42: 634-43.   DOI
23 Dobrek L, Thor P. Glutamate NMDA receptors in pathophysiology and pharmacotherapy of selected nervous system diseases. Postepy Hig Med Dosw (Online) 2011; 65: 338-46.   DOI
24 Shih RH, Wang CY, Yang CM. NF-kappaB signaling pathways in neurological inflammation: a mini review. Front Mol Neurosci 2015; 8: 77.   DOI
25 Oh SH, Yoon MH, Lim KJ, Yu BS, Jee IG, Jung KT. Nefopam downregulates autophagy and c-Jun N-terminal kinase activity in the regulation of neuropathic pain development following spinal nerve ligation. BMC Anesthesiol 2018; 18: 97.   DOI
26 Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, et al. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 2000; 288: 306-13.   DOI
27 Zhou YY, Li Y, Jiang WQ, Zhou LF. MAPK/JNK signalling: a potential autophagy regulation pathway. Biosci Rep 2015; 35: e00199.   DOI
28 Zheng MS, Jin WY, Son KH, Chang HW, Kim HP, Bae KH, et al. The constituents isolated from Peucedanum japonicum Thunb. and their cyclooxygenase (COX) inhibitory activity. Korean J Med Crop Sci 2005; 13: 75-9.
29 Thacker MA, Clark AK, Marchand F, McMahon SB. Pathophysiology of peripheral neuropathic pain: immune cells and molecules. Anesth Analg 2007; 105: 838-47.   DOI
30 Gao YJ, Zhang L, Samad OA, Suter MR, Yasuhiko K, Xu ZZ, et al. JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain. J Neurosci 2009; 29: 4096-108.   DOI
31 Qian M, Fang X, Wang X. Autophagy and inflammation. Clin Transl Med 2017; 6: 24.   DOI
32 Ellis A, Bennett DL. Neuroinflammation and the generation of neuropathic pain. Br J Anaesth 2013; 111: 26-37.   DOI
33 Kasuya Y, Umezawa H, Hatano M. Stress-activated protein kinases in spinal cord injury: focus on roles of p38. Int J Mol Sci 2018; 19: 867.   DOI
34 Lee KM, Kang BS, Lee HL, Son SJ, Hwang SH, Kim DS, et al. Spinal NF-kB activation induces COX-2 upregulation and contributes to inflammatory pain hypersensitivity. Eur J Neurosci 2004; 19: 3375-81.   DOI
35 Brambilla R, Bracchi-Ricard V, Hu WH, Frydel B, Bramwell A, Karmally S, et al. Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med 2005; 202: 145-56.   DOI