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 and Hiroshi Nakanishi ()
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Yoshinori Hayashi: Faculty of Dental Sciences, Kyushu University
Saori Morinaga: Faculty of Dental Sciences, Kyushu University
Jing Zhang: Faculty of Dental Sciences, Kyushu University
Yasushi Satoh: National Defense Medical College
Andrea L. Meredith: University of Maryland School of Medicine
Takahiro Nakata: Faculty of Health Promotional Sciences, Tokoha University
Zhou Wu: Faculty of Dental Sciences, Kyushu University
Shinichi Kohsaka: National Institute of Neuroscience
Kazuhide Inoue: Graduate School of Pharmaceutical Sciences, Kyushu University
Hiroshi Nakanishi: Faculty of Dental Sciences, Kyushu University

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11697

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