BK channels in microglia are required for morphine-induced hyperalgesia

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

Research output: Contribution to journalArticle

24 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

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morphine
Large-Conductance Calcium-Activated Potassium Channels
Hyperalgesia
Microglia
Morphine
Calcium-Activated Potassium Channels
spinal cord
pain
Opioid Receptors
neurons
Arachidonic Acid
Synaptic Transmission
Opioid Analgesics
Neurons
Spinal Cord
Hypersensitivity
Chemical activation
activation

All Science Journal Classification (ASJC) codes

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

Cite this

Hayashi, Y., Morinaga, S., Zhang, J., Satoh, Y., Meredith, A. L., Nakata, T., ... Nakanishi, H. (2016). BK channels in microglia are required for morphine-induced hyperalgesia. Nature communications, 7, [11697]. https://doi.org/10.1038/ncomms11697

BK channels in microglia are required for morphine-induced hyperalgesia. / Hayashi, Yoshinori; Morinaga, Saori; Zhang, Jing; Satoh, Yasushi; Meredith, Andrea L.; Nakata, Takahiro; Take, Hiro; Kohsaka, Shinichi; Inoue, Kazuhide; Nakanishi, Hiroshi.

In: Nature communications, Vol. 7, 11697, 31.05.2016.

Research output: Contribution to journalArticle

Hayashi, Y, Morinaga, S, Zhang, J, Satoh, Y, Meredith, AL, Nakata, T, Take, H, Kohsaka, S, Inoue, K & Nakanishi, H 2016, 'BK channels in microglia are required for morphine-induced hyperalgesia', Nature communications, vol. 7, 11697. https://doi.org/10.1038/ncomms11697
Hayashi Y, Morinaga S, Zhang J, Satoh Y, Meredith AL, Nakata T et al. BK channels in microglia are required for morphine-induced hyperalgesia. Nature communications. 2016 May 31;7. 11697. https://doi.org/10.1038/ncomms11697
Hayashi, Yoshinori ; Morinaga, Saori ; Zhang, Jing ; Satoh, Yasushi ; Meredith, Andrea L. ; Nakata, Takahiro ; Take, Hiro ; Kohsaka, Shinichi ; Inoue, Kazuhide ; Nakanishi, Hiroshi. / BK channels in microglia are required for morphine-induced hyperalgesia. In: Nature communications. 2016 ; Vol. 7.
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