BK channels in microglia are required for morphine-induced hyperalgesia.
BK channels in microglia are required for morphine-induced hyperalgesia.
复制标题
吗啡诱导的痛觉过敏需要小胶质细胞中的BK通道。
DOI：
10.1038/ncomms11697
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发表时间：
2016-05-31
影响因子：
16.6
通讯作者：
Nakanishi H
中科院分区：
文献类型：
--
作者：
Hayashi Y;Morinaga S;Zhang J;Satoh Y;Meredith AL;Nakata T;Wu Z;Kohsaka S;Inoue K;Nakanishi H
尽管吗啡是金标准药物，但长期使用阿片类药物会带来严重的副作用，例如吗啡引起的痛觉过敏 (MIH) 和抗伤害耐受。小胶质细胞到神经元的信号传导与疼痛过敏密切相关。然而，在长期吗啡治疗下控制小胶质细胞状态的分子仍然未知。在这里，我们表明 Ca2+ 激活的 K+ (BK) 通道的小胶质细胞特异性亚型负责 MIH 的产生和抗伤害耐受性。我们发现，长期服用吗啡后，通过 μ-阿片受体的花生四烯酸水平增加导致脊髓中小胶质细胞 BK 通道的唯一激活。沉默 BK 通道辅助 β3 亚基可显着减弱 MIH 的产生和抗伤害耐受性，并增加长期吗啡给药后的神经传递。因此，小胶质细胞特异性 BK 通道有助于 MIH 和抗伤害耐受的产生。 长期使用阿片类药物会导致疼痛敏感性反常增加。在这里，林等人。将小胶质细胞上钾通道的激活与吗啡诱导的小鼠痛觉过敏和抗伤害耐受性联系起来。
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. Long-term use of opioids can lead to a paradoxical increase in pain sensitivity. Here, Hayashi et al. link activation of potassium channels on microglia with morphine-induced hyperalgesia and anti-nociceptive tolerance in mice.