Nathan Berger
Pronouns: he/him
Research Mentor(s): Emily Jutkiewicz
Research Mentor School/College/Department: Pharmacology / Medicine
Program:
Authors: Nathan Berger, Jacob Ormes, Emily Jutkiewicz
Session: Session 2: 10:00 am – 10:50 am
Poster: 54
Abstract
Opioid analgesics can be an effective treatment for pain; however, their use is limited due to factors such as the development of tolerance to their analgesic effects and side effects such as constipation and respiratory depression. Morphine acts on µ-opioid receptors (MORs) to induce analgesia. Previous evidence has shown Gbeta-gamma (GBG) inhibition using the small molecule, gallein, downstream of MOR agonist-induced activation to potentiate morphine-induced antinociception in the warm water tail withdrawal assay (WWTW) without enhancing opioid-related side effects. Therefore, GBG inhibition may be a promising strategy for improving the safety and efficacy of opioid analgesics. Still, it has yet to be demonstrated whether the effects of gallein on MOR-mediated antinociception are MOR agonist-dependent. Therefore, we sought to evaluate the effects of gallein on antinociception -induced by MOR agonists other than morphine. In female and male C57BL/6 mice aged 7-12 weeks, the effects of gallein were investigated on nalbuphine- and buprenorphine-induced antinociception in the WWTW assay. Intracerebroventricular (ICV) pretreatments of gallein (100 nmol) or vehicle were administered 30 min prior to a bolus dose of the partial MOR agonists nalbuphine or buprenorphine and tail withdrawal latencies were recorded every 30 minutes for 3 hours. While nalbuphine did not dose-dependently increase antinociception in the 50°C WWTW assay, antinociception was significantly enhanced when nalbuphine (32 mg/kg) was preceded by gallein pretreatment compared with vehicle. Buprenorphine did produce dose-dependent increases in antinociception in the WWTW assay (55°C). Furthermore, buprenorphine- (0.32 mg/kg) induced antinociception was potentiated by gallein pretreatment compared with vehicle. These data suggest that the effects of gallein on MOR-mediated antinociception do not appear specific to morphine. Future work should confirm these findings, investigate additional MOR agonists, and establish whether gallein acts downstream of other opioid receptor subtypes.
