Loss Of Sur1 Subtype Katp Channel Activity Alters Mechanical Antinociception And Decreases Potassium Flux After Acute Buprenorphine, Damgo, And Fentanyl Administration

Abstract

Opioids are the most commonly used analgesics to treat acute and chronic pain. The development of novel therapeutics and treatments of pain is extremely important due to the opioid epidemic. In the search of new analgesic targets, KATP channels have been selected in part due to their expression in the nervous system and several studies indicating their role in morphine-mediated analgesia. This project used genetic and pharmacological strategies to target SUR1-type KATP channels, to study their role in synthetic and semi-synthetic opioid antinociception and drug-seeking behaviors. Buprenorphine, DAMGO, and fentanyl, opioids used clinically and in research, were assessed for changes in mechanical and thermal sensitivity and locomotion after administration in SUR1-deficient mice. Mechanical sensitivity was attenuated in SUR1-deficient mice, while thermal sensitivity was not affected. Opioid induced hyperlocomotion was only affected after buprenorphine administration. In vitro studies revealed a decrease in potassium flux in the cell bodies of peripheral neurons across all opioid treatments. These results indicate that KATP channel activation by buprenorphine, DAMGO, and fentanyl play a role in opioid analgesia and may also be useful for targeting opioid addiction.