Potentiation of Paclitaxel-Induced Pain Syndrome in Mice by Angiotensin I Converting Enzyme Inhibition and Involvement of Kinins

Autor(es):Mostrar menos -

Brusco, Indiara ^[1] ; Silva, Cassia Regina ^{[2, 1]} ; Trevisan, Gabriela ^[3] ; Velho Gewehr, Camila de Campos ^{[4, 5]} ; Rigo, Flavia Karine ^{[4, 5]} ; Tamiozzo, Lidia La Rocca ^[1] ; Rossato, Mateus Fortes ^[1] ; Tonello, Raquel ^{[6, 1]} ; Dalmolin, Gerusa Duarte ^[1] ; Cabrini, Daniela de Almeida ^[7] ; Gomez, Marcus Vinicius ^{[4, 5]} ; Ferreira, Juliano ^{[6, 1, 3]} ; Oliveira, Sara Marchesan ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Santa Maria, Dept Biochem & Mol Biol, Grad Program Biol Sci Biochem Toxicol, Av Roraima 1000, BR-97105900 Santa Maria, RS - Brazil

^[2] Univ Fed Uberlandia, Inst Genet & Biochem, Uberlandia, MG - Brazil

^[3] Univ Fed Santa Maria, Grad Program Pharmacol, Santa Maria, RS - Brazil

^[4] Univ Fed Minas Gerais, Fac Med, Grad Program Biochem & Mol Pharmacol, Belo Horizonte, MG - Brazil

^[5] Inst Educ & Res Santa Casa, Grad Program Med & Biomed, Belo Horizonte, MG - Brazil

^[6] Univ Fed Santa Catarina, Dept Pharmacol, Florianopolis, SC - Brazil

^[7] Univ Fed Parana, Dept Pharmacol, Curitiba, Parana - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular Neurobiology; v. 54, n. 10, p. 7824-7837, DEC 2017.
• Citações Web of Science: 3

Resumo

Paclitaxel is a chemotherapeutic agent used to treat solid tumours. However, it causes an acute and neuropathic pain syndrome that limits its use. Among the mechanisms involved in neuropathic pain caused by paclitaxel is activation of kinin receptors. Angiotensin converting enzyme (ACE) inhibitors can enhance kinin receptor signalling. The goal of this study was to evaluate the role of kinins on paclitaxel-associated acute pain syndromes (P-APS) and the effect of ACE inhibition on P-APS and paclitaxel-associated chronic peripheral neuropathy (P-CPN) in mice. Herein, we show that paclitaxel caused mechanical allodynia and spontaneous nociceptive behaviour that was reduced by antagonists of kinin receptors B-1 (DALBk and SSR240612) and B-2 (Hoe140 and FR173657). Moreover, enalapril (an ACE inhibitor) enhanced the mechanical allodynia induced by a low dose of paclitaxel. Likewise, paclitaxel injection inhibited ACE activity and increased the expressions of B-1 and B-2 receptors and bradykinin-related peptides levels in peripheral tissue. Together, our data support the involvement of kinin receptors in the P-APS and suggest kinin receptor antagonists to treat this syndrome. Because hypertension is the most frequent comorbidity affecting cancer patients, treatment of hypertension with ACE inhibitors in patients undergoing paclitaxel chemotherapy should be reviewed, since this could enhance the P-APS and P-CPN. (AU)