Ph¦Á1¦Â toxin prevents capsaicin-induced nociceptive behavior and mechanical hypersensitivity without acting on TRPV1 channels

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• 作者：Celio J. Castro-Junior^a ; ¹ ; ^{celiojcjunior@gmail.com} ; Julie Milano^a ; ¹ ; ^{juliemmilano@hotmail.com} ; Alessandra H. Souza^b ; ^{alessandrahubnersouza@gmail.com} ; Juliana F. Silva^b ; Flá ; via K. Rigo^c ; ^{flakrigo@hotmail.com} ; Geruza Dalmolin^c ; ^{gerusadalmolin@yahoo.com.br} ; Marta N. Cordeiro^d ; ^{martadonascimento.phoneutria@gmail.com} ; Michael Richardson^d ; ^{michael@funed.mg.gov.br} ; Alexandre G.A. Barros^b ; ^{xandebarros@gmail.com} ; Renato S. Gomez^b ; ^{renatogomez2000@yahoo.com.br} ; Marco A.R. Silva^b ; ^{romanosilva@gmail.com} ; Christopher Kushmerick^e ; ^{kushmerick@icb.ufmg.br} ; Juliano Ferreira^b ; ^c ; ^{ferreiraj99@gmail.com} ; Marcus V. Gomez^a ; ^b ; ^{marcusvgomez@gmail.com.br} ; ^{marcusvgomez@gmail.com}
• 关键词：Pain ; Ph¦Á1¦Â ; Ca2+ ; Capsaicin ; TRPV1 ; Calcium channel
• 刊名：Neuropharmacology
• 出版年：2013
• 出版时间：August, 2013
• 年：2013
• 卷：71
• 期：Complete
• 页码：237-246
• 全文大小：1747 K

文摘

Ph¦Á1¦Â toxin is a peptide purified from the venom of the armed spider Phoneutria nigriventer, with markedly antinociceptive action in models of acute and persistent pain in rats. Similarly to ziconotide, its analgesic action is related to inhibition of high voltage activated calcium channels with more selectivity for N-type. In this study we evaluated the effect of Ph¦Á1¦Â when injected peripherally or intrathecally in a rat model of spontaneous pain induced by capsaicin. We also investigated the effect of Ph¦Á1¦Â on Ca²⁺ transients in cultured dorsal root ganglia (DRG) neurons and HEK293 cells expressing the TRPV1 receptor. Intraplantar or intrathecal administered Ph¦Á1¦Â reduced both nocifensive behavior and mechanical hypersensitivity induced by capsaicin similarly to that observed with SB366791, a specific TRPV1 antagonist. Peripheral nifedipine and mibefradil did also decrease nociceptive behavior induced by intraplantar capsaicin. In contrast, ¦Ø-conotoxin MVIIA (a selective N-type Ca²⁺ channel blocker) was effective only when administered intrathecally. Ph¦Á1¦Â, MVIIA and SB366791 inhibited, with similar potency, the capsaicin-induced Ca²⁺ transients in DRG neurons. The simultaneous administration of Ph¦Á1¦Â and SB366791 inhibited the capsaicin-induced Ca²⁺ transients that were additive suggesting that they act through different targets. Moreover, Ph¦Á1¦Â did not inhibit capsaicin-activated currents in patch-clamp recordings of HEK293 cells that expressed TRPV1 receptors. Our results show that Ph¦Á1¦Â may be effective as a therapeutic strategy for pain and this effect is not related to the inhibition of TRPV1 receptors.