Paeoniflorin attenuates the neuroinflammatory response in a rat model of chronic constriction injury

Zhou,Jianyu; Wang,Jingxia; Li,Wei; Wang,Chenglong; Wu,Li; Zhang,Jianjun

doi:10.3892/mmr.2017.6371

Paeoniflorin attenuates the neuroinflammatory response in a rat model of chronic constriction injury

Authors:
- Jianyu Zhou
- Jingxia Wang
- Wei Li
- Chenglong Wang
- Li Wu
- Jianjun Zhang
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Affiliations: Department of Traditional Chinese Clinical Pharmacology, School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
Published online on: March 24, 2017 https://doi.org/10.3892/mmr.2017.6371
Pages: 3179-3185

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Abstract

Neuropathic pain remains the most frequent cause of suffering and disability worldwide. Paeoniflorin (PF), a water‑soluble monoterpene glycoside extracted from the roots of Paeonia lactiflora Pall, has a wide range of pharmacological functions. Although the neuroprotective effect of PF has been reported in animal models of neuropathology, no systematic investigation has reported on the analgesic properties of PF in neuropathic pain. The aim of the present study was to investigate whether PF can alleviate neuropathic pain and to examine its possible mechanism. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in rats. Following CCI surgery, the rats were administered with PF for 11 days. Mechanical withdrawal threshold and thermal withdrawal latency were assessed prior to surgery, and on days 3, 7 and 11 post‑surgery. The levels of interleukin (IL)‑1β and tumor necrosis factor (TNF)‑α in the spinal cord were analyzed using enzyme‑linked immunosorbent assays. The activation of astrocytes and microglia were observed using immunostaining. In addition, the phosphorylation of p38 mitogen‑activated protein kinase (p‑p38MAPK) and nuclear factor‑κB (NF‑κB) were examined using western blot analysis. The results indicated that PF significantly attenuated CCI‑induced neuropathic pain and decreased the levels of TNF‑α and IL‑1β proinflammatory cytokines in the spinal cord. Furthermore, PF inhibited the over‑activation of microglia and reduced the elevated expression levels of p‑p38 MAPK and NF‑κB in the spinal cord. These results indicated that PF offers potential as a therapeutic agent for neuropathic pain, which merits further investigation.

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1	Gilron I, Watson CP, Cahill CM and Moulin DE: Neuropathic pain: A practical guide for the clinician. CMAJ. 175:265–275. 2006. View Article : Google Scholar : PubMed/NCBI
2	Cornelius VR, Sauzet O, Williams JE, Ayis S, Farquhar-Smith P, Ross JR, Branford RA and Peacock JL: Adverse event reporting in randomised controlled trials of neuropathic pain: Considerations for future practice. Pain. 154:213–220. 2013. View Article : Google Scholar : PubMed/NCBI
3	Streit WJ, Mrak RE and Griffin WS: Microglia and neuroinflammation: A pathological perspective. J Neuroinflammation. 1:142004. View Article : Google Scholar : PubMed/NCBI
4	Moalem G and Tracey DJ: Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev. 51:240–264. 2006. View Article : Google Scholar : PubMed/NCBI
5	Myers RR, Campana WM and Shubayev VI: The role of neuroinflammation in neuropathic pain: Mechanisms and therapeutic targets. Drug Discov Today. 11:8–20. 2006. View Article : Google Scholar : PubMed/NCBI
6	Wahba M and Waln O: Asterixis related to gabapentin intake: A case report and review. Postgrad Med. 125:139–141. 2013. View Article : Google Scholar : PubMed/NCBI
7	Marchand F, Perretti M and McMahon SB: Role of the immune system in chronic pain. Nat Rev Neurosci. 6:521–532. 2005. View Article : Google Scholar : PubMed/NCBI
8	Milligan ED and Watkins LR: Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci. 10:23–36. 2009. View Article : Google Scholar : PubMed/NCBI
9	Bradesi S: Role of spinal cord glia in the central processing of peripheral pain perception. Neurogastroenterol Motil. 22:499–511. 2010. View Article : Google Scholar : PubMed/NCBI
10	Sweitzer SM, Schubert P and DeLeo JA: Propentofylline, a glial modulating agent, exhibits antiallodynic properties in a rat model of neuropathic pain. J Pharmacol Exp Ther. 297:1210–1217. 2001.PubMed/NCBI
11	Jean YH, Chen WF, Sung CS, Duh CY, Huang SY, Lin CS, Tai MH, Tzeng SF and Wen ZH: Capnellene, a natural marine compound derived from soft coral, attenuates chronic constriction injury-induced neuropathic pain in rats. Br J Pharmacol. 158:713–725. 2009. View Article : Google Scholar : PubMed/NCBI
12	Lin YC, Huang SY, Jean YH, Chen WF, Sung CS, Kao ES, Wang HM, Chakraborty C, Duh CY and Wen ZH: Intrathecal lemnalol, a natural marine compound obtained from Formosan soft coral, attenuates nociceptive responses and the activity of spinal glial cells in neuropathic rats. Behav Pharmacol. 22:739–750. 2011. View Article : Google Scholar : PubMed/NCBI
13	Kim YS, Park HJ, Kim TK, Moon DE and Lee HJ: The effects of Ginkgo biloba extract EGb 761 on mechanical and cold allodynia in a rat model of neuropathic pain. Anesth Analg. 108:1958–1963. 2009. View Article : Google Scholar : PubMed/NCBI
14	Gao T, Hao J, Wiesenfeld-Hallin Z, Wang DQ and Xu XJ: Analgesic effect of sinomenine in rodents after inflammation and nerve injury. Eur J Pharmacol. 721:5–11. 2013. View Article : Google Scholar : PubMed/NCBI
15	Zhou X, Cheng H, Xu D, Yin Q, Cheng L, Wang L, Song S and Zhang M: Attenuation of neuropathic pain by saikosaponin a in a rat model of chronic constriction injury. Neurochem Res. 39:2136–2142. 2014. View Article : Google Scholar : PubMed/NCBI
16	Wu SH, Wu DG and Chen YW: Chemical constituents and bioactivities of plants from the genus Paeonia. Chem Biodivers. 7:90–104. 2010. View Article : Google Scholar : PubMed/NCBI
17	Zhong SZ, Ge QH, Li Q, Qu R and Ma SP: Peoniflorin attentuates Abeta(1–42)-mediated neurotoxicity by regulating calcium homeostasis and ameliorating oxidative stress in hippocampus of rats. J Neurol Sci. 280:71–78. 2009. View Article : Google Scholar : PubMed/NCBI
18	Guo RB, Wang GF, Zhao AP, Gu J, Sun XL and Hu G: Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses. PLoS One. 7:e497012012. View Article : Google Scholar : PubMed/NCBI
19	Nam KN, Yae CG, Hong JW, Cho DH, Lee JH and Lee EH: Paeoniflorin, a monoterpene glycoside, attenuates lipopolysaccharide-induced neuronal injury and brain microglial inflammatory response. Biotechnol Lett. 35:1183–1189. 2013. View Article : Google Scholar : PubMed/NCBI
20	Wu YM, Jin R, Yang L, Zhang J, Yang Q, Guo YY, Li XB, Liu SB, Luo XX and Zhao MG: Phosphatidylinositol 3 kinase/protein kinase B is responsible for the protection of paeoniflorin upon H₂O₂-induced neural progenitor cell injury. Neuroscience. 240:54–62. 2013. View Article : Google Scholar : PubMed/NCBI
21	Liu HQ, Zhang WY, Luo XT, Ye Y and Zhu XZ: Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of Parkinson's disease by activation of adenosine A1 receptor. Br J Pharmacol. 148:314–325. 2006. View Article : Google Scholar : PubMed/NCBI
22	Zhang HR, Peng JH, Cheng XB, Shi BZ, Zhang MY and Xu RX: Paeoniflorin atttenuates amyloidogenesis and the inflammatory responses in a transgenic mouse model of Alzheimer's disease. Neurochem Res. 40:1583–1592. 2015. View Article : Google Scholar : PubMed/NCBI
23	Dong H, Li R, Yu C, Xu T, Zhang X and Dong M: Paeoniflorin inhibition of 6-hydroxydopamine-induced apoptosis in PC12 cells via suppressing reactive oxygen species-mediated PKCδ/NF-κB pathway. Neuroscience. 285:70–80. 2015. View Article : Google Scholar : PubMed/NCBI
24	Liu H, Wang J, Wang J, Wang P and Xue Y: Paeoniflorin attenuates Aβ1-42-induced inflammation and chemotaxis of microglia in vitro and inhibits NF-κB- and VEGF/Flt-1 signaling pathways. Brain Res. 1618:149–158. 2015. View Article : Google Scholar : PubMed/NCBI
25	Chen F, Lu HT and Jiang Y: Purification of paeoniflorin from Paeonia lactiflora Pall. By high-speed counter-current chromatography. J Chromatogr A. 1040:205–208. 2004. View Article : Google Scholar : PubMed/NCBI
26	Bennett GJ and Xie YK: A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 33:87–107. 1988. View Article : Google Scholar : PubMed/NCBI
27	Chaplan SR, Bach FW, Pogrel JW, Chung JM and Yaksh TL: Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 53:55–63. 1994. View Article : Google Scholar : PubMed/NCBI
28	Hargreaves K, Dubner R, Brown F, Flores C and Joris J: A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 32:77–88. 1988. View Article : Google Scholar : PubMed/NCBI
29	Vierck CJ, Acosta-Rua AJ and Johnson RD: Bilateral chronic constriction of the sciatic nerve: A model of long-term cold hyperalgesia. J Pain. 6:507–517. 2005. View Article : Google Scholar : PubMed/NCBI
30	Jaggi AS, Jain V and Singh N: Animal models of neuropathic pain. Fundam Clin Pharmacol. 25:1–28. 2011. View Article : Google Scholar : PubMed/NCBI
31	Chu LW, Chen JY, Yu KL, Cheng KI, Wu PC and Wu BN: Neuroprotective and anti-inflammatory activities of atorvastatin in a rat chronic constriction injury model. Int J Immunopathol Pharmacol. 25:219–230. 2012. View Article : Google Scholar : PubMed/NCBI
32	Wang LX and Wang ZJ: Animal and cellular models of chronic pain. Adv Drug Deliv Rev. 55:949–965. 2003. View Article : Google Scholar : PubMed/NCBI
33	Xu Y, Qiu HQ, Liu H, Liu M, Huang ZY, Yang J, Su YP and Yu CX: Effects of koumine, an alkaloid of Gelsemium elegans Benth., on inflammatory and neuropathic pain models and possible mechanism with allopregnanolone. Pharmacol Biochem Behav. 101:504–514. 2012. View Article : Google Scholar : PubMed/NCBI
34	Costa B, Trovato AE, Colleoni M, Giagnoni G, Zarini E and Croci T: Effect of the cannabinoid CB1 receptor antagonist, SR141716, on nociceptive response and nerve demyelination in rodents with chronic constriction injury of the sciatic nerve. Pain. 116:52–61. 2005. View Article : Google Scholar : PubMed/NCBI
35	Kiguchi N, Kobayashi Y and Kishioka S: Chemokines and cytokines in neuroinflammation leading to neuropathic pain. Curr Opin Pharmacol. 12:55–61. 2012. View Article : Google Scholar : PubMed/NCBI
36	Kawasaki Y, Zhang L, Cheng JK and Ji RR: Cytokine mechanisms of central sensitization: Distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci. 28:5189–5194. 2008. View Article : Google Scholar : PubMed/NCBI
37	Cao H and Zhang YQ: Spinal glial activation contributes to pathological pain states. Neurosci Biobehav Rev. 32:972–983. 2008. View Article : Google Scholar : PubMed/NCBI
38	Chang L and Karin M: Mammalian MAP kinase signalling cascades. Nature. 410:37–40. 2001. View Article : Google Scholar : PubMed/NCBI
39	Obata K, Yamanaka H, Kobayashi K, Dai Y, Mizushima T, Katsura H, Fukuoka T, Tokunaga A and Noguchi K: Role of mitogen-activated protein kinase activation in injured and intact primary afferent neurons for mechanical and heat hypersensitivity after spinal nerve ligation. J Neurosci. 24:10211–10222. 2004. View Article : Google Scholar : PubMed/NCBI
40	Xu JT, Xin WJ, Wei XH, Wu CY, Ge YX, Liu YL, Zang Y, Zhang T, Li YY and Liu XG: p38 activation in uninjured primary afferent neurons and in spinal microglia contributes to the development of neuropathic pain induced by selective motor fiber injury. Exp Neurol. 204:355–365. 2007. View Article : Google Scholar : PubMed/NCBI
41	Xu L, Huang Y, Yu X, Yue J, Yang N and Zuo P: The influence of p38 mitogen-activated protein kinase inhibitor on synthesis of inflammatory cytokine tumor necrosis factor alpha in spinal cord of rats with chronic constriction injury. Anesth Analg. 105:1838–1844, table of contents. 2007. View Article : Google Scholar : PubMed/NCBI
42	Ji RR and Suter MR: p38 MAPK, microglial signaling, and neuropathic pain. Mol Pain. 3:332007. View Article : Google Scholar : PubMed/NCBI
43	Rojewska E, Popiolek-Barczyk K, Jurga AM, Makuch W, Przewlocka B and Mika J: Involvement of pro- and antinociceptive factors in minocycline analgesia in rat neuropathic pain model. J Neuroimmunol. 277:57–66. 2014. View Article : Google Scholar : PubMed/NCBI
44	Sun T, Song WG, Fu ZJ, Liu ZH, Liu YM and Yao SL: Alleviation of neuropathic pain by intrathecal injection of antisense oligonucleotides to p65 subunit of NF-kappaB. Br J Anaesth. 97:553–558. 2006. View Article : Google Scholar : PubMed/NCBI
45	Makarov SS: NF-kappaB as a therapeutic target in chronic inflammation: Recent advances. Mol Med Today. 6:441–448. 2000. View Article : Google Scholar : PubMed/NCBI
46	Niederberger E and Geisslinger G: The IKK-NF-kappaB pathway: A source for novel molecular drug targets in pain therapy. FASEB J. 22:3432–3442. 2008. View Article : Google Scholar : PubMed/NCBI
47	Laughlin TM, Bethea JR, Yezierski RP and Wilcox GL: Cytokine involvement in dynorphin-induced allodynia. Pain. 84:159–167. 2000. View Article : Google Scholar : PubMed/NCBI
48	Wei XH, Yang T, Wu Q, Xin WJ, Wu JL, Wang YQ, Zang Y, Wang J, Li YY and Liu XG: Peri-sciatic administration of recombinant rat IL-1β induces mechanical allodynia by activation of src-family kinases in spinal microglia in rats. Exp Neurol. 234:389–397. 2012. View Article : Google Scholar : PubMed/NCBI