[Altered expression of transporter and analgesic of morphine in neuropathic pain mice].

It is known that morphine is less effective for patients with neuropathic pain, accounting for approximately 70% of cancer patients with severe pain. One of the causes of the decline is reported as a decreased function of the μ-opioid receptor, which binds to the active metabolites of morphine in the mesencephalic ventral tegmental area. However, the details of this mechanism are not understood. We hypothesized that a decrease in the concentration of morphine in the brain reduces its analgesic effect on neuropathic pain, and found that the analgesic effect of morphine was correlated with its concentration in the brain. We examined the reason for the decreased concentration of morphine in the brain in case of neuropathic pain. We discovered increased P-glycoprotein (P-gp) expression in the small intestine, increased expression and activity of UGT2B in the liver, and increased P-gp expression in the brain under conditions of neuropathic pain. In this symposium, we argue that low brain morphine concentration is considered one of the causes of lower sensitivity to morphine in neuropathic pain patients.