Action of Phα1β, a Peptide From the Venom of the Spider Phoneutria nigriventer, on the Analgesic and Adverse Effects Caused by Morphine in Mice

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 Ph alpha 1 beta, 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 Ph alpha 1 beta (30 pmol/site). Repeated treatment with morphine caused tolerance, hyperalgesia, withdrawal syndrome, and constipation, and the Ph alpha 1 beta (.1-30 pmol/site, intrathecal) was able to reverse these effects. Finally, the effects produced by the native form of Ph alpha 1 beta were fully mimicked by a recombinant version of this peptide. Taken together, these data show that Ph alpha 1 beta 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. Perspective: This article presents preclinical evidence for a useful adjuvant drug in opioid treatment. Ph alpha 1 beta, 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. (C) 2014 Published by Elsevier Inc. on behalf of the American Pain Society