Microglia: a newly discovered role in visceral hypersensitivity?
Microglia: a newly discovered role in visceral hypersensitivity?
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DOI：
10.1017/s1740925x07000439
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发表时间：
2006-01-01
影响因子：
--
通讯作者：
Al-Chaer, Elie D.
中科院分区：
文献类型：
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作者：
Saab, Carl Y.;Wang, Jing;Al-Chaer, Elie D.
鉴于越来越多的证据表明神经胶质细胞在疼痛调制中发挥作用，似乎有可能慢性疾病中夸大的内脏疼痛可能是由神经胶质激活来调节的。在这项研究中，我们研究了小胶质细胞在慢性内脏高敏感和先前报道的神经元功能改变的大鼠中的可能作用。实验在新生大鼠结肠刺激(CI)预处理的成年雄性SD大鼠和正常大鼠上进行。研究了Fractalkine(FKN，一种参与神经元到小胶质细胞信号转导的趋化因子)和米诺环素(小胶质细胞的抑制剂)对内脏敏感性的影响。通过记录肌电(EMG)对轻度镇静大鼠分级结直肠扩张(CRD)的反应来评估内脏敏感性。记录注射FKN、米诺环素或赋形剂前后CRD的反应。通过对辐射热的缩足潜伏期来衡量躯体热痛觉过敏。用OX-(42)荧光显微镜观察比较脑梗死组和对照组大鼠脊髓L6-S2区小胶质细胞的分布模式和强度。结果表明：(1)FKN显著促进对照组大鼠对~gt；52%的伤害性CRD的肌电反应，FKN还引起对照组大鼠的热痛觉过敏，与以往的报道一致；(2)与对照组相比，米诺环素显著抑制CI大鼠60min对>；70%的伤害性CRD的肌电反应。米诺环素对脑梗塞大鼠的抗伤害性作用持续180min，注射后60min达高峰。我们的结果表明，FKN增强内脏和躯体的伤害性，而米诺环素抑制内脏超敏反应，这表明小胶质细胞在内脏超敏反应中起作用。
Given the growing body of evidence for a role of glia in pain modulation, it is plausible that the exaggerated visceral pain in chronic conditions might be regulated by glial activation. In this study, we have investigated a possible role for microglia in rats with chronic visceral hypersensitivity and previously documented altered neuronal function. Experiments were performed on adult male Sprague-Dawley rats pre-treated with neonatal colon irritation (CI) and on control rats. Effects of fractalkine (FKN, a chemokine involved in neuron-to-microglia signaling) and of minocycline (an inhibitor of microglia) on visceral sensitivity were examined. Visceral sensitivity was assessed by recording the electromyographic (EMG) responses to graded colorectal distension (CRD) in mildly sedated rats. Responses to CRD were recorded before and after injection of FKN, minocycline or vehicle. Somatic thermal hyperalgesia was measured by latency of paw withdrawal to radiant heat. The pattern and intensity of microglial distribution at L6-S2 in the spinal cord was also compared in rats with CI and controls by fluorescence microscopy using OX-(42). Results show that: (i) FKN significantly facilitated EMG responses to noxious CRD by > 52% in control rats, FKN also induced thermal hyperalgesia in control rats, consistent with previous reports; (2) minocycline significantly inhibited EMG responses to noxious CRD by > 7o% in rats with CI compared to controls 60 min after injection. The anti-nociceptive effect of minocycline lasted for 180 min in rats with CI, reaching peak values 60 min after injection. Our results show that FKN enhances visceral and somatic nociception, whereas minocycline inhibits visceral hypersensitivity in chronically sensitized rats, which indicates a role for microglia in visceral hypersensitivity.