Oxysophocarpine induces anti-nociception and increases the expression of GABAAα1 receptors in mice

Xu,Tingting; Li,Yuxiang; Wang,Haiyan; Xu,Yaqiong; Ma,Lin; Sun,Tao; Ma,Hanxiang; Yu,Jianqiang

doi:10.3892/mmr.2013.1414

Oxysophocarpine induces anti-nociception and increases the expression of GABAAα1 receptors in mice

Authors:
- Tingting Xu
- Yuxiang Li
- Haiyan Wang
- Yaqiong Xu
- Lin Ma
- Tao Sun
- Hanxiang Ma
- Jianqiang Yu
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Affiliations: Department of Anesthesiology, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China, Department of Nursing, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China, Department of Pharmacology, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China, Ningxia Key Laboratory of Craniocerebral Diseases, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China, Department of Anesthesiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China
Published online on: April 4, 2013 https://doi.org/10.3892/mmr.2013.1414
Pages: 1819-1825

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Abstract

Oxysophocarpine (OSC) is an alkaloid extracted from Siphocampylus verticillatus. The aim of this study was to investigate the anti-nociceptive effects of OSC through systemic and intracerebroventricular administration in mice. Moreover, to evaluate its effectiveness and mechanism of action, this study investigated whether OSC altered the expression of γ-aminobutyric acid type A α1 (GABAAα1) receptors in the central nervous system. Thermal and chemical behavioral models of nociception were used to assess the anti‑nociceptive action of OSC. The warm water tail-flick test, the hot‑plate test, acetic acid-induced abdominal constriction and formalin‑induced pain were used in mice. OSC was administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.). Results showed that OSC (80 mg/kg, i.p.) significantly increased the tail withdrawal threshold with a peak effect of 25.46% maximal possible effect (MPE) at 60 min (P﹤0.01). Additionally, OSC (80 mg/kg) increased the positive staining of GABAAα1 receptors in cells. In conclusion, OSC administration is suggested to have anti-nociceptive effects on the central and peripheral nervous systems. The involvement of GABAA receptors in the anti-nociceptive activity of OSC is currently being investigated.

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1	Millan MJ: Descending control of pain. Prog Neurobiol. 66:355–474. 2002. View Article : Google Scholar
2	Malcangio M and Bowery NG: GABA and its receptors in the spinal cord. Trends Pharmacol Sci. 17:457–462. 1996. View Article : Google Scholar : PubMed/NCBI
3	Zhang JT, Wang W and Duan ZH: Progress of research and application of matrine-type alkaloids. Prog Mod Biomed. 7:541–544. 2007.(In Chinese).
4	Rodrigues AL, da Silva GL, Mateussi AS, et al: Involvement of monoaminergic system in the antidepressant-like effect of the hydroalcoholic extract of Siphocampylus verticillatus. Life Sci. 70:1347–1358. 2002. View Article : Google Scholar : PubMed/NCBI
5	Trentin AP, Santos AR, Miguel OG, Pizzolatn MG, Yunes RA and Calixto JB: Mechanisms involved in the antinociceptive effect in mice of the hydroalcoholic extract of Siphocampylus verticillatus. J Pharm Pharmacol. 49:567–572. 1997. View Article : Google Scholar : PubMed/NCBI
6	Li ZHR: The pharmaceutical effect and clinical development of kushenin. West China J Pharm Sci. 18:435–437. 2003.(In Chinese).
7	Wang XH, Huang SK and Lin P: Pharmacokinetics and pharmacodynamics of sophocarpine and oxysophocarpine. J China Pharm Univ. 23:161–164. 1992.(In Chinese).
8	Yan L and Jiang YX: Studies of analgesia effect of oxysophoridien. Chin Tradit Herb Drugs. 37:1061–1062. 2006.(In Chinese).
9	Grant GJ, Vermenulen K, Zakowski MI, Stener M, Turndorf H and Langerman L: Prolonged analgesia and decreased toxicity with liposomal morphine in a mouse model. Anesth Analg. 79:706–709. 1994.PubMed/NCBI
10	Goyal R and Anil K: Protective effect of alprazolam in acute immobilization stress-induced certain behavioral and biochemical alterations in mice. Pharmacol Rep. 59:284–290. 2007.PubMed/NCBI
11	Eddy NB and Leimbach D: Synthetic analgesics. II Dithienylbutenyl- and dithienylbutylamines. J Pharmacol Exp Ther. 107:385–393. 1953.PubMed/NCBI
12	Qian LW, Dai WH and Wang LL: Toxicity study on sophocarpine and oxysophocarpine in mice. Chin J Exp Tradit Med Formulae. 18:256–258. 2012.(In Chinese).
13	Dongmo AB, Nguelefack T and Lacaille-Dubois MA: Antinociceptive and anti-inflammatory activities of Acacia pennata wild (Mimosaceae). J Ethnopharmacol. 98:201–206. 2005. View Article : Google Scholar : PubMed/NCBI
14	Corrêa CR and Calixto JB: Evidence for participation of B1 and B2 kinin receptors in formalin-induced nociceptive response in the mouse. Br J Pharmacol. 110:193–198. 1993.PubMed/NCBI
15	Vaz ZR, Filho VC, Yunes R and Calixto JB: Antinociceptive action of 2-(4-bromobenzoyl)-3-methyl-4,6-dimethoxy benzofuran, a novel xanthoxyline derivative on chemical and thermal models of nociception in mice. J Phamacol Exp Ther. 278:304–312. 1996.PubMed/NCBI
16	Santos AR and Calixto JB: Further evidence for the involvement of tachykinin receptor subtypes in formalin and capsaicin models of pain in mice. Neuropeptides. 31:381–389. 1997. View Article : Google Scholar : PubMed/NCBI
17	Xu SY, Bian RL and Chen X: Methods of pharmacological experiments. 3rd ed. The People’s Medical Publishing House; Beijing: pp. 7022002
18	Le Bars D, Gozariu M and Cadden SW: Animal models of nociception. Pharmacol Rev. 53:597–652. 2001.
19	Thomsen M, Wörtwein G, Olesen MV, et al: Involvement of Y(5) receptors in neuropeptide Y agonist-induced analgesic-like effect in the rat hot plate test. Brain Res. 1155:49–55. 2002. View Article : Google Scholar : PubMed/NCBI
20	Tjølsen A, Berge OG, Hunskaar S, Rosland JH and Hole K: The formalin test: an evaluation of the method. Pain. 51:5–17. 1992.
21	Chau T: Pharmacological methods in the control of inflammation. Modern Methods in Pharmacology. Chang JY and Lewis AJ: Alan R. Liss; New York: pp. 195–212. 1989
22	Walwyn WM, Matsuka Y, Arai D, et al: HSV-1-mediated NGF delivery delays nociceptive deficits in a genetic model of diabetic neuropathy. Exp Neurol. 198:260–270. 2006. View Article : Google Scholar : PubMed/NCBI
23	Rujjanawate C, Kanjanapothi D and Panthony A: Pharmacological effect and toxicity of alkaloids from Gelsemium elegans Benth. J Ethnopharmacol. 89:91–95. 2003. View Article : Google Scholar : PubMed/NCBI
24	Hunskaar S and Hole K: The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain. 30:103–114. 1987. View Article : Google Scholar : PubMed/NCBI
25	Koster R, Anderson M and De Beer EJ: Acetic acid for analgesic screening. Fed Proc. 18:412–416. 1959.
26	Hendershot LC and Forsaith J: Antagonism of the frequency of phenylquinone-induced writhing in the mouse by weak analgesics and nonanalgesics. J Pharmacol Exp Ther. 125:237–240. 1959.PubMed/NCBI
27	Collier HO, Dinneen LC, Johnson CA and Schneider C: The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br J Pharmacol Chemother. 32:295–310. 1968. View Article : Google Scholar : PubMed/NCBI
28	Martire M, Castaldo P, D’Amico M, Preziosi P, Annuzito L and Taglialatela M: M channels containing KCNQ2 subunits modulate norepinephrine, aspartate, and GABA release from hippocampal nerve terminals. J Neurosci. 24:592–597. 2004. View Article : Google Scholar : PubMed/NCBI
29	Lujan R: Subcellular regulation of metabotropic GABA receptors in the developing cerebellum. Cerebellum. 6:123–129. 2007. View Article : Google Scholar : PubMed/NCBI
30	Condés-Lara M, Rojas-Piloni G, Martínez-Lorenzana G, López-Hidalgo M and Rodríguez-Jiménez J: Hypothalamospinal oxytocinergic antinociception is mediated by GABAergic and opiate neurons that reduce A-delta and C fiber primary afferent excitation of spinal cord cells. Brain Res. 1247:38–49. 2009.
31	Barnard EA, Skolnick P, Olsen RW, et al: International Union of Pharmacology. XV Subtypes of γ-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function. Pharmacol Rev. 50:291–313. 1998.PubMed/NCBI
32	Knabl J, Witschi R, Hösl K, et al: Reversal of pathological pain through specific spinal GABA_A receptors subtypes. Nature. 451:330–334. 2008. View Article : Google Scholar : PubMed/NCBI
33	Whiting PJ, Bonnert TP, McKernan RM, et al: Molecular and functional diversity of the expanding GABA_A receptor gene family. Ann N Y Acad Sci. 868:645–653. 1999. View Article : Google Scholar : PubMed/NCBI
34	Sieghart W: Structure, pharmacology, and function of GABA_A receptor subtypes. Adv Pharmacol. 54:231–263. 2006. View Article : Google Scholar
35	Nutt D: GABA_A receptors: subtypes, regional distribution, and function. J Clin Sleep Med. 2:S7–S11. 2006.
36	Möhler H, Fritschy JM and Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 300:2–8. 2002.
37	Sieghart W and Sperk G: Subunit composition, distribution and function of GABA(A) receptor subtypes. Curr Top Med Chem. 2:795–816. 2002. View Article : Google Scholar : PubMed/NCBI
38	Pirker S, Schwarzer C, Wieselthaler A, Sieghart W and Sperk G: GABA(A) receptors: immunocytochemical distribution of 13 subunits in the adult rat brain. Neuroscience. 101:815–850. 2000. View Article : Google Scholar : PubMed/NCBI
39	Crestani F, Martin JR, Möhler H and Rudolph U: Mechanism of action of the hypnotic zolpidem in vivo. Br J Pharmacol. 131:1251–1254. 2000. View Article : Google Scholar : PubMed/NCBI
40	Melzack R and Wall PD: Pain mechanism: a new theory. Science. 150:971–979. 1965. View Article : Google Scholar : PubMed/NCBI
41	Wall PD: The substantia gelatinosa. A gate control mechanism set across sensory pathway. Trends Neurosci. 3:221–224. 1980. View Article : Google Scholar
42	Redecker C, Luhmann HJ, Hagemann G, Fritschy JM and Witte OW: Differential downregulation of GABA_A receptor subunits in widespread brain regions in the freeze-lesion model of local cortical malformations. J Neurosci. 20:5045–5053. 2000.PubMed/NCBI