title: Analgesic effect in rodents of native and recombinant Ph alpha 1beta toxin, a high-voltage-activated calcium channel blocker isolated from armed spider venom.
abstract: Calcium influx through neuronal voltage-sensitive calcium channels (VSCC S) mediates nociceptive information in the spinal dorsal horn. In fact, spinally administered VSCC S blockers, such as omega-conotoxin MVIIA, have analgesic effect apart of their low therapeutic index and many side effects. Here we study the analgesic potential of Ph alpha 1beta, a calcium channel blocker, in rodent models of acute and persistent pain. Spinally administered Ph alpha 1beta showed higher efficacy and long-lasting analgesia in a thermal model of pain, when compared with omega-conotoxin MVIIA. Moreover, Ph alpha 1beta was more effective and potent than omega-conotoxin MVIIA not only to prevent, but especially to reverse, previously installed persistent chemical and neuropathic pain. Furthermore, the analgesic action of both toxins are related with the inhibition of Ca2+-evoked release of pro-nociceptive neurotransmitter, glutamate, from rat spinal cord synaptosomes and decrease of glutamate overflow in cerebrospinal fluid. When side effects were assessed, we found that Ph alpha 1beta had a therapeutic index wider than omega- conotoxin MVIIA. Finally, recombinant Ph alpha 1beta expressed in Escherichia coli showed marked analgesic activity similar to the native toxin. Taken together, the present study demonstrates that native and recombinant Ph alpha 1beta have analgesic effects in rodent models of pain, suggesting that this toxin may have potential to be used as a drug in the control of persistent pathological pain.
authors.affiliation: Departamento de Farmacologia, ICB, UFMG, 31270-901 Belo Horizonte, MG, Brazil Departamento de Quimica UFSM, 97105-900 Santa Maria, RS, Brazil Fundação Ezequiel Dias, Belo Horizonte, MG, Brazil Departamento de Bioquimica e Imunologia, ICB, UFMG, 31270-901 Belo Horizonte, MG, Brazil Nucleo Pós Graduação, Santa Casa de Belo Horizonte, Brazil Robarts Research Institute, University of Western Ontario, London, Ontario, Canada Laboratório de Neurociência, Faculdade de Medicina, UFMG, 30130-100, Brazil.
authors.forename: Alessandra H
authors.initials: AH
authors.lastname: Souza
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
authors.forename: Marta do Nascimento
authors.initials: MDN
authors.lastname: Cordeiro
authors.forename: Luciene Bruno
authors.initials: LB
authors.lastname: Vieira
authors.forename: Celio J
authors.initials: CJ
authors.lastname: De Castro
authors.forename: Gabriela
authors.initials: G
authors.lastname: Trevisan
authors.forename: Helton
authors.initials: H
authors.lastname: Reis
authors.forename: Ivana Assis
authors.initials: IA
authors.lastname: Souza
authors.forename: Michael
authors.initials: M
authors.lastname: Richardson
authors.forename: Marco A M
authors.initials: MAM
authors.lastname: Prado
authors.forename: Vânia F
authors.initials: VF
authors.lastname: Prado
authors.forename: Marcus Vinicius
authors.initials: MV
authors.lastname: Gomez
mesh_terms: D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000302:isolation & purification*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D006930:Hyperalgesia / Q000175:diagnosis / Q000503:physiopathology* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects*; D011994:Recombinant Proteins / Q000378:metabolism; D013111:Spider Venoms / Q000737:chemistry* / Q000235:genetics
chemical_list: D000700:Analgesics; D002121:Calcium Channel Blockers; D011994:Recombinant Proteins; D013111:Spider Venoms
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