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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2016

Open Access 01-12-2016 | Research article

Anti-allodynic effect of intrathecal processed Aconitum jaluense is associated with the inhibition of microglial activation and P2X7 receptor expression in spinal cord

Authors: Jihoon Yang, Keun Suk Park, Jae Joon Yoon, Hong-Beom Bae, Myung Ha Yoon, Jeong Il Choi

Published in: BMC Complementary Medicine and Therapies | Issue 1/2016

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Abstract

Background

For their analgesic and anti-arthritic effects, Aconitum species have been used in folk medicine in some East Asian countries. Although their analgesic effect is attributed to its action on voltage-dependent sodium channels, they also suppress purinergic receptor expression in dorsal root ganglion neurons in rats with neuropathic pain. In vitro study also demonstrated that the Aconitum suppresses ATP-induced P2X7 receptor (P2X7R)-mediated inflammatory responses in microglial cell lines. Herein, we examined the effect of intrathecal administration of thermally processed Aconitum jaluense (PA) on pain behavior, P2X7R expression and microglial activation in a rat spinal nerve ligation (SNL) model.

Methods

Mechanical allodynia induced by L5 SNL in Sprague-Dawley rats was measured using the von Frey test to evaluate the effect of intrathecal injection of PA. Changes in the expression of P2X7R in the spinal cord were examined using RT-PCR and Western blot analysis. In addition, the effect of intrathecal PA on microglial activation was evaluated by immunofluorescence.

Results

Intrathecal PA attenuated mechanical allodynia in a dose-dependent manner showing both acute and chronic effects with 65 % of the maximal possible effect. The expression and production of spinal P2X7R was increased five days after SNL, but daily intrathecal PA injection significantly inhibited the increase to the level of naïve animals. Immunofluorescence of the spinal cord revealed a significant increase in P2X7R expression and activation of microglia in the dorsal horn, which was inhibited by intrathecal PA treatment. P2X7R co-localized with microglia marker, but not neurons.

Conclusions

Intrathecal PA exerts anti-allodynic effects in neuropathic pain, possibly by suppressing P2X7R production and expression as well as reducing microglial activation in the spinal cord.
Literature
1.
Xu H, Arita H, Hayashida M, Zhang L, Sekiyama H, Hanaoka K. Pain-relieving effects of processed Aconiti tuber in CCI-neuropathic rats. J Ethnopharmacol. 2006;103(3):392–7.CrossRefPubMed
2.
Li M, He J, Jiang LL, Ng ES, Wang H, Lam FF, Zhang YM, Tan NH, Shaw PC. The anti-arthritic effects of Aconitum vilmorinianum, a folk herbal medicine in Southwestern China. J Ethnopharmacol. 2013;147(1):122–7.CrossRefPubMed
3.
Feng L, Liu WK, Deng L, Tian JX, Tong XL. Clinical efficacy of aconitum-containing traditional Chinese medicine for diabetic peripheral neuropathic pain. Am J Chin Med. 2014;42(1):109–17.CrossRefPubMed
4.
Ameri A. The effects of Aconitum alkaloids on the central nervous system. Prog Neurobiol. 1998;56(2):211–35.CrossRefPubMed
5.
Friese J, Gleitz J, Gutser UT, Heubach JF, Matthiesen T, Wilffert B, Selve N. Aconitum sp. alkaloids: the modulation of voltage-dependent Na + channels, toxicity and antinociceptive properties. Eur J Pharmacol. 1997;337(2-3):165–74.CrossRefPubMed
6.
Ren W, Yuan L, Li J, Huang XJ, Chen S, Zou DJ, Liu X, Yang XZ. Ethanolic extract of Aconiti Brachypodi Radix attenuates nociceptive pain probably via inhibition of voltage-dependent Na(+) channel. Afr J Tradit Complement Altern Med. 2012;9(4):574–83.PubMedPubMedCentral
7.
Mika J, Zychowska M, Popiolek-Barczyk K, Rojewska E, Przewlocka B. Importance of glial activation in neuropathic pain. Eur J Pharmacol. 2013;716(1-3):106–19.CrossRefPubMed
8.
Aldskogius H, Kozlova EN. Microglia and neuropathic pain. CNS Neurol Disord Drug Targets. 2013;12(6):768–72.CrossRefPubMed
9.
Ou S, Zhao YD, Xiao Z, Wen HZ, Cui J, Ruan HZ. Effect of lappaconitine on neuropathic pain mediated by P2X3 receptor in rat dorsal root ganglion. Neurochem Int. 2011;58(5):564–73.CrossRefPubMed
10.
Li J, Ren W, Huang XJ, Zou DJ, Hu X. Bullatine A, a diterpenoid alkaloid of the genus Aconitum, could attenuate ATP-induced BV-2 microglia death/apoptosis via P2X receptor pathways. Brain Res Bull. 2013;97:81–5.CrossRefPubMed
11.
Inoue K, Tsuda M. Purinergic systems, neuropathic pain and the role of microglia. Exp Neurol. 2012;234(2):293–301.CrossRefPubMed
12.
He WJ, Cui J, Du L, Zhao YD, Burnstock G, Zhou HD, Ruan HZ. Spinal P2X(7) receptor mediates microglia activation-induced neuropathic pain in the sciatic nerve injury rat model. Behav Brain Res. 2012;226(1):163–70.CrossRefPubMed
13.
Kobayashi K, Takahashi E, Miyagawa Y, Yamanaka H, Noguchi K. Induction of the P2X7 receptor in spinal microglia in a neuropathic pain model. Neurosci lett. 2011;504(1):57–61.CrossRefPubMed
14.
Jeong SH, Heo BH, Park SH, Kim WM, Lee HG, Yoon MH, Choi JI. Spinal noradrenergic modulation and the role of the alpha-2 receptor in the antinociceptive effect of intrathecal nefopam in the formalin test. Korean J Pain. 2014;27(1):23–9.CrossRefPubMed
15.
Kim SH, Chung JM. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain. 1992;50(3):355–63.CrossRefPubMed
16.
Shim SH, Kim JS, Kang SS, Son KH, Bae K. A new diterpenoid alkaloid from Aconitum jaluense. J Asian Natur Prod Res. 2006;8(5):451–5.CrossRef
17.
Shim SH, Kim JS, Kang SS, Son KH, Bae K. Alkaloidal constituents from Aconitum jaluense. Arch Pharm Res. 2003;26(9):709–15.CrossRefPubMed
18.
Choi JI, Kim WM, Yoon MH, Lee HG. Antiallodynic Effect of Thalidomide and Morphine on Rat Spinal Nerve Ligation-induced Neuropathic Pain. Korean J Pain. 2010;23(3):172–8.CrossRefPubMedPubMedCentral
19.
20.
Singhuber J, Zhu M, Prinz S, Kopp B. Aconitum in traditional Chinese medicine: a valuable drug or an unpredictable risk? J Ethnopharmacol. 2009;126(1):18–30.CrossRefPubMed
21.
Zhou G, Tang L, Zhou X, Wang T, Kou Z, Wang Z. A review on phytochemistry and pharmacological activities of the processed lateral root of Aconitum carmichaelii Debeaux. J Ethnopharmacol. 2015;160:173–93.CrossRefPubMed
22.
Zhou H, Wong YF, Cai X, Liu ZQ, Jiang ZH, Bian ZX, Xu HX, Liu L. Suppressive effects of JCICM-6, the extract of an anti-arthritic herbal formula, on the experimental inflammatory and nociceptive models in rodents. Biol Pharm Bull. 2006;29(2):253–60.CrossRefPubMed
23.
Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci. 2007;10(11):1361–8.CrossRefPubMed
24.
Calvo M, Bennett DL. The mechanisms of microgliosis and pain following peripheral nerve injury. Exp Neurol. 2012;234(2):271–82.CrossRefPubMed
25.
Choi YS, Jun IG, Kim SH, Park JY. Intrathecal lamotrigine attenuates mechanical allodynia and suppresses microglial and astrocytic activation in a rat model of spinal nerve ligation. Yonsei Med J. 2013;54(2):321–9.CrossRefPubMedPubMedCentral
26.
Toda S, Sakai A, Ikeda Y, Sakamoto A, Suzuki H. A local anesthetic, ropivacaine, suppresses activated microglia via a nerve growth factor-dependent mechanism and astrocytes via a nerve growth factor-independent mechanism in neuropathic pain. Mol Pain. 2011;7:2.CrossRefPubMedPubMedCentral
27.
Tsuda M, Tozaki-Saitoh H, Inoue K. Purinergic system, microglia and neuropathic pain. Curr Opin Pharmacol. 2012;12(1):74–9.CrossRefPubMed
28.
Trang T, Beggs S, Salter MW. ATP receptors gate microglia signaling in neuropathic pain. Exp Neurol. 2012;234(2):354–61.CrossRefPubMed
29.
Jarvis MF. The neural-glial purinergic receptor ensemble in chronic pain states. Trends Neurosci. 2010;33(1):48–57.CrossRefPubMed
Metadata
Title
Anti-allodynic effect of intrathecal processed Aconitum jaluense is associated with the inhibition of microglial activation and P2X7 receptor expression in spinal cord
Authors
Jihoon Yang
Keun Suk Park
Jae Joon Yoon
Hong-Beom Bae
Myung Ha Yoon
Jeong Il Choi
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2016
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1201-2

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