Activation of spinal extracellular signal-regulated kinases (ERK) 1/2 is associated with the development of visceral hyperalgesia of the bladder.
Activation of spinal extracellular signal-regulated kinases (ERK) 1/2 is associated with the development of visceral hyperalgesia of the bladder.
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DOI：
10.1016/j.pain.2011.05.017
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发表时间：
2011-09
期刊：
影响因子：
7.4
通讯作者：
Gereau RW 4th
中科院分区：
文献类型：
--
作者：
Lai HH;Qiu CS;Crock LW;Morales MEP;Ness TJ;Gereau RW 4th
脊髓背角神经元细胞外信号调节激酶（ERK）1/2的激活在外周炎症后躯体超敏反应和脊髓中枢敏感化的发展中起重要作用。然而，关于脊髓ERK 1/2在内脏痛觉过敏的发展中的作用的数据很少。在这里，我们研究了在无害和有害的扩张后，在小鼠的发炎（环磷酰胺治疗）和非发炎膀胱的腰骶脊髓ERK 1/2的激活。我们还将脊髓ERK 1/2激活与腹内脏反应（VMR）量化的膨胀诱发的膀胱伤害性感受相关。环磷酰胺治疗（膀胱炎症）引起膀胱痛觉过敏和异常性疼痛增加膀胱扩张，明显的VMR刺激反应曲线的向上和向下移动相比，非炎症小鼠。膀胱痛觉过敏的发展与L 6-S1脊髓背角和双侧深层ERK 1/2激活的增强有关。通过鞘内注射上游MEK抑制剂U 0126功能性阻断脊髓ERK 1/2活性可减弱扩张诱发的膀胱伤害性感受，并导致VMR刺激-反应曲线显著下移。总之，我们提供了功能和免疫组织化学证据，表明腰骶脊髓ERK 1/2的激活与原发性内脏（膀胱）痛觉过敏的发生有关。我们的研究结果表明，内脏伤害性信息在腰骶脊髓水平通过激活ERK 1/2信号的异常处理可能有助于慢性膀胱疼痛的炎症背景下。
Activation of extracellular signal-regulated kinases (ERK) 1/2 in dorsal horn neurons is important for the development of somatic hypersensitivity and spinal central sensitization after peripheral inflammation. However, data regarding the roles of spinal ERK1/2 in the development of visceral hyperalgesia are sparse. Here we studied the activation of ERK1/2 in the lumbosacral spinal cord following innocuous and noxious distention of the inflamed (cyclophosphamide- treated) and non-inflamed urinary bladder in mice. We also correlated the spinal ERK1/2 activation to distention-evoked bladder nociception as quantified by the abdominal visceromotor response (VMR). Cyclophosphamide treatment (bladder inflammation) evoked increased bladder hyperalgesia and allodynia to bladder distention, as evident from an upward and leftward shift of the VMR stimulus-response curve compared to that of non-inflamed mice. Development of bladder hyperalgesia was associated with robust enhancement of ERK1/2 activation in the dorsal horn and deeper laminae bilaterally in the L6-S1 spinal cord. Functional blockade of spinal ERK1/2 activity via intrathecal administration of the upstream MEK inhibitor U0126 attenuated distention-evoked bladder nociception, and caused a significant downward shift of the VMR stimulus-response curve. In summary, we have provided functional and immunohistochemical evidence that activation of lumbosacral spinal ERK1/2 is associated with the development of primary visceral (bladder) hyperalgesia. Our results suggest that aberrant processing of visceral nociceptive information at the level of the lumbosacral spinal cord via activation of ERK1/2 signaling may contribute to chronic bladder pain in the context of inflammation.
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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通讯作者：
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作者：
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