title: Effect of ω-conotoxin MVIIA and Phα1β on paclitaxel-induced acute and chronic pain.
abstract: The treatment with the chemotherapeutic agent paclitaxel produces a painful peripheral neuropathy, and is associated with an acute pain syndrome in a clinically significant number of patients. However, no standard therapy has been established to manage the acute pain or the chronic neuropathic pain related to paclitaxel. In the present study, we evaluated the analgesic potential of two N-type voltage-gated calcium channel (VGCC) blockers, ω-conotoxin MVIIA and Phα1β, on acute and chronic pain induced by paclitaxel. Adult male rats were treated with four intraperitoneal injections of paclitaxel (1+1+1+1mg/kg, in alternate days) and the development of mechanical hyperalgesia was evaluated 24h (acute painful stage) or 15days (chronic painful stage) after the first paclitaxel injection. Not all animals showed mechanical hyperalgesia 24h after the first paclitaxel injection, but those that showed developed a more intense mechanical hyperalgesia at the chronic painful stage. Intrathecal administration (i.t.) of ω-conotoxin MVIIA (3-300pmol/site) or Phα1β (10-300pmol/site) reduced the mechanical hyperalgesia either at the acute or at the chronic painful stage induced by paclitaxel. When administered at the acute painful stage, ω-conotoxin MVIIA (300pmol/site, i.t.) and Phα1β (300pmol/site, i.t.) prevented the worsening of chronic mechanical hyperalgesia. Furthermore, Phα1β (30-300pmol/site, i.t.) elicited less adverse effects than ω-conotoxin MVIIA (10-300 pmol/site, i.t.). Taken together, our data evidence the involvement of N-type VGCC in pain sensitization induced by paclitaxel and point out the potential of Phα1β as a safer alternative than ω-conotoxin MVIIA to treat the pain related to paclitaxel.
authors.affiliation: Programa de Pós-graduação em Farmacologia Bioquímica e Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Núcleo de Pós-graduação, Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil.
authors.forename: Flávia K
authors.initials: FK
authors.lastname: Rigo
authors.forename: Gerusa D
authors.initials: GD
authors.lastname: Dalmolin
authors.forename: Gabriela
authors.initials: G
authors.lastname: Trevisan
authors.forename: Raquel
authors.initials: R
authors.lastname: Tonello
authors.forename: Mariane A
authors.initials: MA
authors.lastname: Silva
authors.forename: Mateus F
authors.initials: MF
authors.lastname: Rossato
authors.forename: Jonatas Z
authors.initials: JZ
authors.lastname: Klafke
authors.forename: Marta do N
authors.initials: Mdo N
authors.lastname: Cordeiro
authors.forename: Célio J
authors.initials: CJ
authors.lastname: Castro Junior
authors.forename: Danuza
authors.initials: D
authors.lastname: Montijo
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Gomez
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
mesh_terms: D000208:Acute Disease; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002908:Chronic Disease; D008297:Male; D017239:Paclitaxel / Q000009:adverse effects*; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000494:pharmacology / Q000627:therapeutic use*; D020960:omega-Conotoxins / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000700:Analgesics; C583821:Phalpha1beta toxin, Phoneutria nigriventer; D013111:Spider Venoms; D020960:omega-Conotoxins; C078452:ziconotide; D017239:Paclitaxel
keywords: Calcium channel blockers; Chemotherapy; Neuropathy; Peptide toxins; Phoneutria nigriventer