A Novel Approach to Avoiding Opioid Tolerance

Chronic opioid use leads to narcotic misuse by altering neuronal µ-opioid receptor (MOR) function in peripheral nociceptors, which results in both tolerance to the analgesic effect and opioid-induced hyperalgesia (OIH). This series of animal experiments was designed to explore the potential therapeutic applications of this observation.

Chronic morphine administration was shown to result in antinociceptive tolerance and OIH in wild-type mice but not in MOR-knockout mice, although spinal microglial activation occurred in both groups. By selectively altering MOR genes, the researchers determined that loss of MOR signaling in dorsal root ganglion nociceptors prevented tolerance and OIH. Then, the investigators studied the combination of morphine…