| First Author | Hayashi Y | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 11697 | PubMed ID | 27241733 |
| Mgi Jnum | J:239914 | Mgi Id | MGI:5882018 |
| Doi | 10.1038/ncomms11697 | Citation | Hayashi Y, et al. (2016) BK channels in microglia are required for morphine-induced hyperalgesia. Nat Commun 7:11697 |
| abstractText | 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 Ca(2+)-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 mu-opioid receptors leads to the sole activation of microglial BK channels in the spinal cord. Silencing BK channel auxiliary beta3 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. |
