Pharmacological switch in Abeta-fiber stimulation-induced spinal transmission in mice with partial sciatic nerve injury.
Pharmacological switch in Abeta-fiber stimulation-induced spinal transmission in mice with partial sciatic nerve injury.
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DOI：
10.1186/1744-8069-4-25
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发表时间：
2008-07-11
期刊：
影响因子：
3.3
通讯作者：
Ueda H
中科院分区：
文献类型：
--
作者：
Matsumoto M;Xie W;Ma L;Ueda H
我们之前已经证明了不同的脊髓传递参与了由使用Neurometer®在幼稚小鼠中电刺激Aβ、Aδ或C纤维引起的伤害性行为。在这项研究中，我们试图重新描述部分坐骨神经损伤引起的脊髓传递的改变，在伤害性行为和脊髓背角细胞外信号调节激酶（pERK）的磷酸化。Aβ纤维反应（2000 Hz）在未处理小鼠中被AMPA/红藻氨酸拮抗剂CNQX选择性阻断，在电刺激诱导的缩爪（EPW）试验中，在损伤小鼠中被NMDA受体拮抗剂MK-801和AP-5超敏但被阻断。虽然Aδ-纤维反应（250 Hz）也因神经损伤而超敏，但通过NMDA受体的Aδ-纤维反应的药理学特征没有改变。相反，C-纤维反应（5-Hz）被神经损伤降低敏感性。此外，Aδ-和C-纤维刺激，而不是Aβ-纤维刺激显着增加pERK阳性神经元的数量在浅脊髓背角的幼稚小鼠，和相应的拮抗剂中使用的EPW测试抑制这种增加。在神经损伤的小鼠中，Aβ和Aδ纤维刺激显著增加了浅层脊髓背角中pERK阳性神经元的数量，而C纤维刺激减少了这一数量。MK-801和AP-5可抑制Aβ刺激诱导的神经损伤特异性pERK升高，但CNQX不抑制。然而，Aβ和Aδ刺激不影响背根神经节中pERK阳性神经元的数量或大小，而C纤维刺激选择性地减少pERK阳性神经元的数量。这些结果表明，在神经损伤的动物中，Aβ纤维感知通过NMDA受体介导的机制新传递到脊髓神经元，这些神经元最初仅接受Aδ和C纤维介导的疼痛传递。这种Aβ纤维脊髓传递的药理学开关可能是神经性异常性疼痛的潜在机制。
We have previously demonstrated that different spinal transmissions are involved in the nociceptive behavior caused by electrical stimulation of Aβ-, Aδ- or C-fibers using a Neurometer® in naïve mice. In this study, we attempted to pharmacologically characterize the alteration in spinal transmission induced by partial sciatic nerve injury in terms of nociceptive behavior and phosphorylation of extracellular signal-regulated kinase (pERK) in the spinal dorsal horn. Aβ-fiber responses (2000-Hz), which were selectively blocked by the AMPA/kainate antagonist CNQX in naïve mice, were hypersensitized but blocked by the NMDA receptor antagonists MK-801 and AP-5 in injured mice in an electrical stimulation-induced paw withdrawal (EPW) test. Although Aδ-fiber responses (250-Hz) were also hypersensitized by nerve injury, there was no change in the pharmacological characteristics of Aδ-fiber responses through NMDA receptors. On the contrary, C-fiber responses (5-Hz) were hyposensitized by nerve injury. Moreover, Aδ- and C-, but not Aβ-fiber stimulations significantly increased the number of pERK-positive neurons in the superficial spinal dorsal horns of naïve mice, and corresponding antagonists used in the EPW test inhibited this increase. In mice with nerve injury, Aβ- as well as Aδ-fiber stimulations significantly increased the number of pERK-positive neurons in the superficial spinal dorsal horn, whereas C-fiber stimulation decreased this number. The nerve injury-specific pERK increase induced by Aβ-stimulation was inhibited by MK-801 and AP-5, but not by CNQX. However, Aβ- and Aδ-stimulations did not affect the number or size of pERK-positive neurons in the dorsal root ganglion, whereas C-fiber-stimulation selectively decreased the number of pERK-positive neurons. These results suggest that Aβ-fiber perception is newly transmitted to spinal neurons, which originally receive only Aδ- and C-fiber-mediated pain transmission, through NMDA receptor-mediated mechanisms, in animals with nerve injury. This pharmacological switch in Aβ-fiber spinal transmission could be a mechanism underlying neuropathic allodynia.
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影响因子：
25
作者：
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通讯作者：
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