BK channels in microglia are required for morphine-induced hyperalgesia

Yoshinori Hayashi, Saori Morinaga, Jing Zhang, Yasushi Satoh, Andrea L. Meredith, Takahiro Nakata, Zhou Wu, Shinichi Kohsaka, Kazuhide Inoue, Hiroshi Nakanishi

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Although morphine is a gold standard medication, long-term opioid use is associated with serious side effects, such as morphine-induced hyperalgesia (MIH) and anti-nociceptive tolerance. Microglia-to-neuron signalling is critically involved in pain hypersensitivity. However, molecules that control microglial cellular state under chronic morphine treatment remain unknown. Here we show that the microglia-specific subtype of Ca2+ -activated K+ (BK) channel is responsible for generation of MIH and anti-nociceptive tolerance. We find that, after chronic morphine administration, an increase in arachidonic acid levels through the μ-opioid receptors leads to the sole activation of microglial BK channels in the spinal cord. Silencing BK channel auxiliary β3 subunit significantly attenuates the generation of MIH and anti-nociceptive tolerance, and increases neurotransmission after chronic morphine administration. Therefore, microglia-specific BK channels contribute to the generation of MIH and anti-nociceptive tolerance.

Original languageEnglish
Article number11697
JournalNature communications
Volume7
DOIs
Publication statusPublished - May 31 2016

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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