TRPV1 channel inhibition contributes to the antinociceptive effects of Croton macrostachyus extract in mice

BMC Complementary and Alternative Medicine

João Batista Calixto²  Edinéia Lemos de Andrade³  Ana Flavia Paszcuk³  Rafael Cypriano Dutra¹  Télesphore Benoît Nguelefack³ 

[1] Laboratory of Autoimmunity and Immunopharmacology, Campus Araranguá, Universidade Federal de Santa Catarina, Araranguá, 88900-000, SC, Brazil;Centre of inovation and preclinic studies (CIEnP), Av. Luiz Boiteux Piazza 1302, Cachoeira do Bom Jesus, Florianópolis, SC, Brazil;Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina UFSC, Campus Universitario, Rua Ferreira Lima 82, Trindade, Florianopolis, 88049-900, SC, Brazil

关键词: TRPV1;    Antinociceptive;    Inflammatory pain;    Neuropathic pain;    Croton macrostachyus;   

Others  :  1222679
DOI  :  10.1186/s12906-015-0816-z

 received in 2014-12-19, accepted in 2015-08-10,  发布年份 2015

【 摘 要 】

Background

Previous study showed that extracts from Croton macrostachyus (Euphorbiaceae) exhibit analgesic effects in acute pain models. The present study evaluates the antinociceptive properties of the methanol/methylene chloride extract (MECM) of the stem bark of this plant using mice models of persistent inflammatory and neuropathic pain, and assesses its mechanism of action.

Methods

MECM was tested on Complete Freund adjuvant (CFA)-induced persistent thermal and mechanical pain, neuropathic pain induced by partial sciatic nerve ligation (PSNL), prostaglandin E ₂(PGE ₂ )-induced acute mechanical hyperalgesia, as well as on nociception induced by capsaicin in mice. Mechanical hyperalgesia was assessed using von Frey hair in awake mice. The mechanism of action of MECM was evaluated by using glibenclamide on PGE ₂ -induced hyperalgesia or rimonabant on capsaicin-induced pain.

Results

MECM administered orally at the doses of 250 and 500 mg/kg, induced long lasting and significant antihyperalgesic effects on CFA-inflammatory and PSNL-induced neuropathic pain. MECM significantly reduced the mechanical hyperalgesia induced by PGE ₂either when administered preventively or therapeutically. MECM also significantly and time dependently inhibited the capsaicin-induced nociception. These effects were not affected by glibenclamide or by rimonabant.

Conclusions

The present results demonstrate that the oral administration of MECM to mice resulted in long lasting antihyperalgesic activity in inflammatory and neuropathic pain as well as in acute and persistent pain. The mechanism underlying the long lasting MECM antihyperalgesic effect is currently unknown, but might be mediated, at least partially, through the modulation of TRPV1 receptors.

【 授权许可】

   
2015 Nguelefack et al.

【 图 表 】

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【 参考文献 】

• [1]Wen YR, Tan PH, Cheng JK, Liu YC, Ji RR. Microglia: a promising target for treating neuropathic and postoperative pain, and morphine tolerance. J Formos Med Assoc. 2011; 110:487-94.
• [2]Li Y, Zhang Y, Liu D, H-y L, W-g H, Dong Y-s. Curcumin attenuates diabetic neuropathic pain by downregulating TNF-α in a rat model. Int J Med Sci. 2013; 10:377-81.
• [3]Luo H, Xu IS, Chen Y, Yang F, Yu L, Li G-X et al.. Behavioral and electrophysiological evidence for the differential functions of TRPV1 at early and late stages of chronic Inflammatory Nociception in Rats. Neurochem Res. 2008; 33:2151-8.
• [4]Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med. 2005; 352:1324-34.
• [5]Calixto JB, Beirith A, Ferreira J, Santos AR, Filho VC, Yunes RA. Naturally occurring antinociceptive substances from plants. Phytother Res. 2000; 14:401-18.
• [6]Gurib-Fakim A. Medicinal plants: traditions of yesterday and drugs of tomorrow. Mol Aspects Med. 2006; 27:1-93.
• [7]Albrecht JED. Livre de main de graine d’arbre du Kenya. Kenya de graine de sylviculture de GTZ, Centre Muguga; 1993.
• [8]Bein E. Arbres et arbustes utiles en Erythrée. Unité régionale de conservation de sol (RSCU), Nairobi; 1996.
• [9]Kamanyi A, Mbiantcha M, Nguelefack TB, Ateufack G, Watcho P, Ndontsa BL, Tane P. Anti-Nociceptive and anti-inflammatory activities of extracts from the stem bark of Croton macrostachyus (Euphorbiaceae) in mice and rats. J Compl Alter Med. 2009; 6:Art 20.
• [10]Tene M, Ndontsa BL, Tane P, Tamokou J, Kuiate J-R. Antimicrobial diterpenoids and triterpenoids from the stem bark of Croton macrostachyus. Int J Biol Chem Sci. 2009; 3:538-44.
• [11]Nguelefack TB, Dutra RC, Paszcuk AF, Andrade EL, Tapondjou LA, Calixto JB. Antinociceptive activities of the methanol extract of the bulbs of Dioscorea bulbifera L. var sativa in mice is dependent of NO-cGMP-ATP-sensitive-K + channel activation. J Ethnopharmacol. 2010; 128:567-74.
• [12]Quintao NL, Medeiros R, Santos AR, Campos MM, Calixto JB. The effects of diacerhein on mechanical allodynia in inflammatory and neuropathic models of nociception in mice. Anesth Analg. 2005; 101:1763-9.
• [13]Da Silva KA, Manjavachi MN, Paszcuk AF, Pivatto M, Viegas C, Bolzani VS et al.. Plant derived alkaloid (−)-cassine induces anti-inflammatory and anti-hyperalgesics effects in both acute and chronic inflammatory and neuropathic pain models. Neuropharmacol. 2012; 62:967-77.
• [14]Sotocinal SG, Sorge RE, Zaloum A, Tuttle AH, Martin LJ, Wieskopf JS et al.. The Rat Grimace Scale: a partially automated method for quantifying pain in the laboratory rat via facial expressions. Mol Pain. 2011; 7:55. BioMed Central Full Text
• [15]Meotti FC, Luiz AP, Pizzolatti MG, Kassuya CA, Calixto JB, Santos AR. Analysis of the antinociceptive effect of the flavonoid myricitrin: evidence for a role of the L-arginine-nitric oxide and protein kinase C pathways. J Pharmacol Exp Ther. 2006; 316:789-96.
• [16]Binzen U, Greffrath W, Hennessy S, Bausen M, Saaler-Reinhardt S, Treede R-D. Co-expression of the voltage-gated potassium channel Kv1.4 with transient receptor potential channels (TRPV1 and TRPV2) and the cannabinoid receptor CB1 in rat dorsal root ganglion neurons. Neuroscience. 2006; 142:527-39.
• [17]Hagues G, Costentin J, Duterte-Boucher D. Modulation of morphine and alcohol motor stimulant effects by cannabinoid receptors ligands. Behav Brain Res. 2007; 178:274-82.
• [18]Suárez AI, Compagnone RS, Salazar-Bookaman MM, Tillett S, Monache FD, Di Giulio C et al.. Antinociceptive and anti-inflammatory effects of Croton malambo bark aqueous extract. J Ethnopharmacol. 2003; 88:11-4.
• [19]Santos FA, Jeferson FA, Santos CC, Silveira ER, Rao VSN. Antinociceptive effect of leaf essential oil from Croton sonderianus in mice. Life Sci. 2005; 77:2953-63.
• [20]Zhao J, Fang F, Yu L, Wang G, Yang L. Anti-nociceptive and anti-inflammatory effects of Croton crassifolius ethanol extract. J Ethnopharmacol. 2012; 42:367-73.
• [21]Raghavendra V, DeLeo JA. The role of astrocytes and microglia in persistent pain. In: Non-neuronal cells in the nervous system: function and dysfunction. Hertz L, editor. Elsevier, Amsterdam; 2003: p.951-66.
• [22]Hui J, Zhang Z-J, Zhang X, Shen Y, Gao Y-J. Repetitive hyperbaric oxygen treatment attenuates Complete Freund’s Adjuvant-induced pain and reduces glia-mediated neuroinflammation in the spinal cord. J Pain. 2013; 14:747-58.
• [23]Peng HY, Chen GD, Hsieh MC, Lai CY, Huang YP, Lin TB. Spinal SGK1/GRASP-1/Rab4 is involved in complete Freund’s adjuvant-induced inflammatory pain via regulating dorsal horn GluR1-containing AMPA receptor trafficking in rats. Pain. 2012; 153:2380-92.
• [24]Huang CP, Chen HN, Su HL, Hsieh CL, Chen WH, Lai ZR, et al. Electroacupuncture reduces carrageenan- and CFA-induced inflammatory pain accompanied by changing the expression of Nav1.7 and Nav1.8, rather than Nav1.9, in mice dorsal root ganglia. Evid Based Complement Alternat Med. 2013. doi:10.1155/2013/312184.
• [25]Liang L, Fan L, Tao B, Yaster M, Tao YX. Protein Kinase B/Akt is required for Complete Freund’s Adjuvant-induced upregulation of Nav1.7 and Nav1.8 in primary sensory neurons. J Pain. 2013; 14:638-47.
• [26]Cunha TM, Waldiceu A, Jr V, Fukada SY, Guerrero ATG, Santodomingo-Garzón T et al.. TNF-α and IL-1β mediate inflammatory hypernociception in mice triggered by B1 but not B2 kinin receptor. Eur J Pharmacol. 2007; 573:221-9.
• [27]Ma W, Eisenach JC. Four PGE 2 EP receptors are up-regulated in injured nerve following partial sciatic nerve ligation. Exp Neurol. 2003; 183:581-92.
• [28]Ocaña M, Del Pozo E, Barrios M, Robles LI, Baeyens JM. An ATP-dependent potassium channel blocker antagonizes morphine analgesia. Eur J Pharmacol. 1990; 186:377-8.
• [29]Alves D, Duarte I. Involvement of ATP-sensitive K + channels in the peripheral antinociceptive effect induced by dipyrone. Eur J Pharmacol. 2002; 444:47-52.
• [30]Alves DP, Tatsuo MA, Leite R, Duarte ID. Diclofenac-induced peripheral antinociception is associated with ATP-sensitive K + channels activation. Life Sci. 2004; 74:2577-91.
• [31]Vale ML, Rolim DE, Cavalcante IF, Ribeiro RA, Souza MH. Role of NO/cGMP/KATP pathway in antinociceptive effect of sildenafil in zymosan writhing response in mice. Inflamm Res. 2007; 56:83-8.
• [32]Romero TR, Duarte ID. Involvement of ATP-sensitive K + channels in the peripheral antinociceptive effect induced by the alpha(2)-adrenoceptor agonist xylazine. J Pharmacol Sci. 2009; 111:323-37.
• [33]Loram LC, Fuller A, Fick LG, Cartmell T, Poole S, Mitchell D. Cytokine profiles during carrageenan-induced inflammatory hyperalgesia in rat muscle and hind paw. J Pain. 2007; 8:127-36.
• [34]Claudino RF, Kassuya CA, Ferreira J, Calixto JB. Pharmacological and molecular characterization of the mechanisms involved in prostaglandin E 2 -induced mouse paw edema. J Pharmacol Exp Ther. 2006; 318:611-8.
• [35]Wang W, Cao X, Liu C, Liu L. Cannabinoid WIN 55,212-2 inhibits TRPV1 in trigeminal ganglion neurons via PKA and PKC pathways. Neurol Sci. 2012; 33:79-85.
• [36]Schnizler K, Shutov LP, Van Kanegan MJ, Merrill MA, Nichols B, McKnight GS et al.. Protein kinase A anchoring via AKAP150 is essential for TRPV1 modulation by forskolin and prostaglandin E2 in mouse sensory neurons. J Neurosci. 2008; 28:4904-17.
• [37]Cao E, Cordero-Morales JF, Liu B, Qin F, Julius D. TRPV1 channels are intrinsically heat sensitive and negatively regulated by phosphoinositide lipids. Neuron. 2013; 77:667-79.
• [38]Yang Y, Yang H, Wang Z, Varadaraj K, Kumari SS, Mergler S et al.. Cannabinoid receptor 1 suppresses transient receptor potential vanilloid 1-induced inflammatory responses to corneal injury. Cell Signal. 2013; 25:501-11.