title: Antiallodynic effect and side effects of Phα1β, a neurotoxin from the spider Phoneutria nigriventer: comparison with ω-conotoxin MVIIA and morphine.
abstract: Phα1β is a potent toxin obtained from the spider Phoneutria nigriventer that blocks neuronal voltage-sensitive Ca(2+) channels. This study compared the antiallodynic effects of Phα1β, ω-conotoxin MVIIA and morphine in mice and their side effects in rats. Mechanical allodynia was measured in mice receiving single intrathecal administration of Phα1β, ω-conotoxin MVIIA or morphine before or after the incisional plantar procedure. The effect of the treatments on cardiovascular profile and global neurological were evaluated in rats. The expression of pro or anti-inflammatory cytokines of human polymorph mononuclear cells was also evaluated. Preemptive use of ω-conotoxin MVIIA (1.0 or 10 pmol/site) or morphine (1000 pmol/site) induced shorter antiallodynic effect than Phα1β (100 pmol/site) in mice. Post-incision administration of Phα1β (200 pmol/site) induced longer mechanical antiallodynic effect than ω-conotoxin MVIIA (1.0 or 10 pmol/site) or morphine (1000 pmol/site). Intrathecal injection of Phα1β (200 pmol/site) and morphine (433 pmol/site) did not change while ω-conotoxin MVIIA (100 pmol/site) increased the heart rate in rats 3 h after its administration. Phα1β (200 pmol/site), ω-conotoxin MVIIA (100 pmol/site) and morphine (433 pmol/site) did not change mean arterial pressure 0.5 and 3 h after their administration. The treatments did not alter neurological performance assessed by global neurological evaluation and open-field test. The tested drugs did not induced expression of pro or anti-inflammatory cytokines in CD4 monocytes. In conclusion, preemptive administration Phα1β in mice induced longer antiallodynic effect than ω-conotoxin MVIIA and morphine. Phα1β also induced a longer mechanical antiallodynic effect than ω-conotoxin MVIIA and morphine when used after the surgical incision. The present results suggest that Phα1β has a potential application in the management of postoperative pain with low side effects.
authors.affiliation: Laboratório de Neurociência, UFMG, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: A H
authors.initials: AH
authors.lastname: de Souza
authors.forename: M C
authors.initials: MC
authors.lastname: Lima
authors.forename: C C
authors.initials: CC
authors.lastname: Drewes
authors.forename: J F
authors.initials: JF
authors.lastname: da Silva
authors.forename: K C L
authors.initials: KC
authors.lastname: Torres
authors.forename: E M R
authors.initials: EM
authors.lastname: Pereira
authors.forename: C J
authors.initials: CJ
authors.lastname: de Castro Junior
authors.forename: L B
authors.initials: LB
authors.lastname: Vieira
authors.forename: M N
authors.initials: MN
authors.lastname: Cordeiro
authors.forename: M
authors.initials: M
authors.lastname: Richardson
authors.forename: R S
authors.initials: RS
authors.lastname: Gomez
authors.forename: M A
authors.initials: MA
authors.lastname: Romano-Silva
authors.forename: J
authors.initials: J
authors.lastname: Ferreira
authors.forename: M V
authors.initials: MV
authors.lastname: Gomez
mesh_terms: D000328:Adult; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007278:Injections, Spinal; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009460:Neurologic Examination; D009479:Neuropeptides / Q000633:toxicity*; D009498:Neurotoxins / Q000633:toxicity*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000633:toxicity*; D020960:omega-Conotoxins / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D016207:Cytokines; D009479:Neuropeptides; D009498:Neurotoxins; D013111:Spider Venoms; C098736:Tx3 neurotoxin; D020960:omega-Conotoxins; D009020:Morphine