Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl- homeostasis

Treatment of pain with morphine leads to paradoxical hyperalgesia. The authors provide evidence that morphine-induced hyperalgesia is a result of downregulation of the chloride transporter KCC2 in spinal lamina I neurons. Microglial expression of P2X4 receptors and release of BDNF may underlie this change in neuronal chloride homeostasis and morphine-induced hyperalgesia.