Effect of the morphine/heroin vaccine on opioid and non-opioid drug-induced antinociception in mice

Eur J Pharmacol. 2021 Jan 15:891:173718. doi: 10.1016/j.ejphar.2020.173718. Epub 2020 Nov 7.

Abstract

Pain is a common symptom in patients with opioid use disorder (OUD), which increases synthetic and illicit synthetic opioid abuse and even fatalities due to opioid overdose. Many FDA-approved drugs are available for the treatment of OUD, however, the use of these medications is limited, mainly due to the development of various side effects. Active vaccination is a new therapeutic approach but the resulting antibodies may compromise the use and efficiency of opioid and non-opioid drugs. In this study, we evaluated whether the antibodies produced by the morphine/heroin vaccine (M-TT) would alter the antinociceptive effects of opioid and non-opioid drugs. Female Balb-c mice were immunized with the M-TT vaccine. A solid-phase antibody-capture ELISA was used for monitoring antibody titer responses after each booster dose in vaccinated animals, followed by tail-flick testing. This study found that the M-TT vaccine did not affect the antinociception induced by different doses of morphine or the ability of non-opioid and synthetic opioid drugs to decrease thermal pain. Moreover, the combination of vaccination and naloxone increased the time-course of morphine antagonism relative to either vaccination or naloxone alone. These results suggest that the antibody titers generated by the M-TT vaccine 1) are capable of reducing morphine-induced antinociception and 2) are selective enough not to alter antinociception induced by non-opioid or synthetic drugs. These characteristics support its potential as a treatment agent for patients with symptoms of pain comorbid to OUD.

Keywords: Active vaccination; Antibodies; M-TT vaccine; Morphine; Nociception.

MeSH terms

  • Analgesics, Non-Narcotic / pharmacology*
  • Analgesics, Opioid / immunology
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Antibodies / blood*
  • Dose-Response Relationship, Drug
  • Female
  • Gabapentin / pharmacology*
  • Immunization
  • Immunogenicity, Vaccine*
  • Mice
  • Mice, Inbred BALB C
  • Morphine / immunology
  • Morphine / pharmacology*
  • Morphine Dependence / drug therapy*
  • Morphine Dependence / immunology
  • Nociception / drug effects*
  • Vaccines / pharmacology*

Substances

  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Antibodies
  • Vaccines
  • Gabapentin
  • Morphine