Effects of aquaporin 4 deficiency on morphine analgesia and chronic tolerance: a study at spinal level

Recent reports showed that aquaporin 4 (AQP4) deficiency potentiated morphine analgesia but attenuated chronic morphine-induced tolerance in hot-plate test, predominantly reflecting supraspinal pain response. The present study investigated the effects of AQP4 deficiency on morphine analgesia and tolerance using tail flick test, primarily reflecting spinal response. It was found that (1) chronic morphine treatment resulted in decreased expression of spinal AQP4 in mice detected by Western blotting analysis; (2) in tail flick test, AQP4 knockout mice displayed significant impaired morphine analgesia without influencing the progress of chronic tolerance; and (3) the expressions of mu-opioid receptor (MuOR) and glutamate transporter 1 (GLT-1) in AQP4 knockout mice spinal cord were lower than those in wild-type mice, whereas chronic morphine-induced alteration characteristics of spinal MuOR or GLT-1 expression were not affected by AQP4 deficiency. In conclusion, AQP4 deficiency attenuated morphine acute antinociception but did not affect chronic tolerance in tail flick test, implying a role for spinal AQP4 in morphine analgesia but not in chronic tolerance.