title: An evaluation of the antinociceptive effects of Phα1β, a neurotoxin from the spider Phoneutria nigriventer, and ω-conotoxin MVIIA, a cone snail Conus magus toxin, in rat model of inflammatory and neuropathic pain.
abstract: Voltage-sensitive calcium channels (VSCCs) underlie cell excitability and are involved in the mechanisms that generate and maintain neuropathic and inflammatory pain. We evaluated in rats the effects of two VSCC blockers, ω-conotoxin MVIIA and Phα1β, in models of inflammatory and neuropathic pain induced with complete Freund's adjuvant (CFA) and chronic constrictive injury (CCI), respectively. We also evaluated the effects of the toxins on capsaicin-induced Ca(2+) influx in dorsal root ganglion (DRG) neurons obtained from rats exposed to both models of pain. A single intrathecal injection of Phα1β reversibly inhibits CFA and CCI-induced mechanical hyperalgesia longer than a single injection of ω-conotoxin MVIIA. Phα1β and MVIIA also inhibited capsaicin-induced Ca(2+) influx in DRG neurons. The inhibitory effect of Phα1β on capsaicin-induced calcium transients in DRG neurons was greater in the CFA model of pain, while the inhibitory effect of ω-conotoxin MVIIA was greater in the CCI model. The management of chronic inflammatory and neuropathic pain is still a major challenge for clinicians. Phα1β, a reversible inhibitor of VSCCs with a preference for N-type Ca(2+) channels, has potential as a novel therapeutic agent for inflammatory and neuropathic pain. Clinical studies are necessary to establish the role of Phα1β in the treatment of chronic pain.
authors.affiliation: Programa de Pós-Graduação em Medicina Molecular, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Alessandra Hubner
authors.initials: AH
authors.lastname: de Souza
authors.forename: Célio J
authors.initials: CJ
authors.lastname: Castro
authors.forename: Flavia Karine
authors.initials: FK
authors.lastname: Rigo
authors.forename: Sara Marchesan
authors.initials: SM
authors.lastname: de Oliveira
authors.forename: Renato Santiago
authors.initials: RS
authors.lastname: Gomez
authors.forename: Danuza Montijo
authors.initials: DM
authors.lastname: Diniz
authors.forename: Marcia Helena
authors.initials: MH
authors.lastname: Borges
authors.forename: Marta Nascimento
authors.initials: MN
authors.lastname: Cordeiro
authors.forename: Marco Aurélio Romano
authors.initials: MA
authors.lastname: Silva
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
authors.forename: Marcus Vinicius
authors.initials: MV
authors.lastname: Gomez
mesh_terms: D000700:Analgesics / Q000302:isolation & purification / Q000627:therapeutic use*; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000473:pathology; D009498:Neurotoxins / Q000302:isolation & purification / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012908:Snails; D013111:Spider Venoms / Q000302:isolation & purification / Q000627:therapeutic use*; D013112:Spiders; D020960:omega-Conotoxins / Q000302:isolation & purification / Q000627:therapeutic use*
chemical_list: D000700:Analgesics; D009498:Neurotoxins; C583821:Phalpha1beta toxin, Phoneutria nigriventer; D013111:Spider Venoms; D020960:omega-Conotoxins; C053423:Conus magus toxin