Acute nerve injury induces long-term potentiation of C-fiber evoked field potentials in spinal dorsal horn of intact rat.
Acute nerve injury induces long-term potentiation of C-fiber evoked field potentials in spinal dorsal horn of intact rat.
复制标题
DOI：
--
复制
发表时间：
2004-10
期刊：
影响因子：
--
通讯作者：
Hong-Mei Zhang;Li-Jun Zhou;Xiao-Dong Hu;Neng-Wei Hu;Tong Zhang;Xian-Guo Liu
中科院分区：
文献类型：
--
作者：
Hong-Mei Zhang;Li-Jun Zhou;Xiao-Dong Hu;Neng-Wei Hu;Tong Zhang;Xian-Guo Liu
神经损伤产生持久的神经性疼痛，表现为异常性疼痛、痛阈降低和痛觉过敏、对有害刺激的反应增加。持续异常疼痛的机制尚不清楚。我们之前的工作表明，坐骨神经的强直电刺激会引起脊髓背角C纤维诱发场电位的长时程增强（LTP），这被认为是病理性疼痛的突触模型。在本研究中，我们测试了神经损伤（已被证明会产生神经性疼痛）是否会在完整大鼠中诱导脊髓 LTP。记录坐骨神经电刺激（10-20 V，0.5 ms，1/min）产生的脊髓背角 C 纤维诱发场电位。为了诱导 C 纤维诱发场电位的 LTP，应用了三种类型的有害刺激。 (1) 电强直刺激（40 V，0.5 ms 脉冲，100 Hz，持续 1 秒，以 10 秒的间隔重复四次）。 (2) 在刺激电极远端 4-5 mm 处横断坐骨神经。 (3)用镊子在刺激电极远端4-5mm处挤压坐骨神经4次(从远端到近端间隔1mm，间隔10s)，模拟电破伤风刺激。急性神经损伤是通过刺激电极远端的坐骨神经横断或挤压坐骨神经造成的。我们发现，通过切割或挤压坐骨神经造成的神经损伤会产生C纤维诱发场电位的LTP，持续到实验结束（3-9小时），并且在神经横切前10分钟用利多卡因预处理坐骨神经完全阻断神经横断引起的LTP。 NMDA 受体拮抗剂 AP5 阻断神经横断诱导的 LTP。神经横断产生的LTP不能被电强直刺激进一步增强，而单次强直电刺激诱导的LTP可以通过坐骨神经横断进一步增强。然而，当多次强直电刺激使LTP达到饱和时，神经横断并不影响脊髓LTP。我们得出的结论是，急性神经损伤会诱导完整动物中 C 纤维诱发场电位的 LTP，并且神经横断比电强直刺激更能诱导脊髓 LTP。结果进一步支持了 C 纤维诱发场电位的 LTP 可能是神经性疼痛的基础这一观点。
Nerve injury produces a long lasting neuropathic pain, manifested as allodynia, a decrease in pain threshold and hyperalgesia, an increase in response to noxious stimuli. The mechanism underlying the lasting abnormal pain is not well understood. Our previous works have shown that electrical tetanic stimulation of the sciatic nerve induces long-term potentiation (LTP) of C-fiber evoked field potentials in the spinal dorsal horn, which is considered as a synaptic model of pathological pain. In the present study we tested if nerve injury, which is proved to produce neuropathic pain, induced the spinal LTP in intact rats. C-fiber evoked field potentials in spinal dorsal horn produced by electrical stimulation (10-20 V, 0.5 ms, 1/min) of the sciatic nerve were recorded. For induction of LTP of C-fiber evoked field potentials, three types of noxious stimuli were applied. (1) Electrical tetanic stimulation (40 V, 0.5 ms pulses at 100 Hz for 1 s repeated four times at 10 s intervals). (2) Transection of the sciatic nerve at 4-5 mm distal to the stimulation electrode. (3) Crushing the sciatic nerve with a forceps four times at 4-5 mm distal to stimulation electrode (from distal to proximal with 1 mm spacing at 10 s intervals), which simulated electrical tetanic stimulation. Acute nerve injury was made by either transection of the sciatic nerve at the distal to the stimulating electrode or crushing the sciatic nerve. We found that nerve injury by cutting or crushing the sciatic nerve produced LTP of C-fiber evoked field potentials lasting until the end of the experiments (3-9 h), and that pretreatment of the sciatic nerve with lidocaine 10 min prior to the nerve transectoin completely blocked LTP induced by nerve transection. The nerve transection-induced LTP was blocked by NMDA receptor antagonist AP5. LTP produced by nerve transection could not be further potentiated by electrical tetanic stimulation, while LTP induced by single electrical tetanic stimulation could be further potentiated by transection of the sciatic nerve. However, when LTP was saturated by several times of electrical tetanic stimulation, nerve transection did not affect the spinal LTP. We conclude that acute nerve injury induces LTP of C-fiber evoked field potentials in intact animals and that nerve transection is more powerful than electrical tetanic stimulation for induction of the spinal LTP. The results further support the notion that LTP of C-fiber evoked field potentials may underlie neuropathic pain.