title: Action of Phα1β, a peptide from the venom of the spider Phoneutria nigriventer, on the analgesic and adverse effects caused by morphine in mice.
abstract: Opioids are standard therapy for the treatment of pain; however, adverse effects limit their use. Voltage-gated calcium channel blockers may be used to increase opioid analgesia, but their effect on opioid-induced side effects is little known. Thus, the goal of this study was to evaluate the action of the peptide Phα1β, a voltage-gated calcium channel blocker, on the antinociceptive and adverse effects produced by morphine in mice. A single administration of morphine (3-10 mg/kg) was able to reduce heat nociception as well as decrease gastrointestinal transit. The antinociception caused by a single injection of morphine was slightly increased by an intrathecal injection of Phα1β (30 pmol/site). Repeated treatment with morphine caused tolerance, hyperalgesia, withdrawal syndrome, and constipation, and the Phα1β (.1-30 pmol/site, intrathecal) was able to reverse these effects. Finally, the effects produced by the native form of Phα1β were fully mimicked by a recombinant version of this peptide. Taken together, these data show that Phα1β was effective in potentiating the analgesia caused by a single dose of morphine as well as in reducing tolerance and the adverse effects induced by repeated administration of morphine, indicating its potential use as an adjuvant drug in combination with opioids.
  
  
  CONCLUSIONS
  This article presents preclinical evidence for a useful adjuvant drug in opioid treatment. Phα1β, a peptide calcium channel blocker, could be used not only to potentiate morphine analgesia but also to reduce the adverse effects caused by repeated administration of morphine.
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Raquel
authors.initials: R
authors.lastname: Tonello
authors.affiliation: Núcleo de Pós-graduação, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil.
authors.forename: Flávia
authors.initials: F
authors.lastname: Rigo
authors.affiliation: Núcleo de Pós-graduação, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Gewehr
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil; Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Trevisan
authors.affiliation: Núcleo de Pós-graduação, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil.
authors.forename: Elizete Maria Rita
authors.initials: EM
authors.lastname: Pereira
authors.affiliation: Núcleo de Pós-graduação, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil.
authors.forename: Marcus Vinicius
authors.initials: MV
authors.lastname: Gomez
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil; Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: ferreiraj99@gmail.com.
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D060829:Arthropod Proteins / Q000737:chemistry / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005772:Gastrointestinal Transit / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use*; D009270:Naloxone; D009292:Narcotic Antagonists; D059226:Nociceptive Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D060829:Arthropod Proteins; D002121:Calcium Channel Blockers; D009292:Narcotic Antagonists; D010455:Peptides; D009270:Naloxone; D009020:Morphine
keywords: Calcium channel blocker; constipation; hyperalgesia; opioid; tolerance; withdrawal syndrome