Characterization of three different sensory fibers by use of neonatal capsaicin treatment, spinal antagonism and a novel electrical stimulation-induced paw flexion test
Characterization of three different sensory fibers by use of neonatal capsaicin treatment, spinal antagonism and a novel electrical stimulation-induced paw flexion test
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DOI：
10.1186/1744-8069-2-16
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发表时间：
2006-05-08
期刊：
影响因子：
3.3
通讯作者：
Ueda, Hiroshi
中科院分区：
文献类型：
--
作者：
Matsumoto, Misaki;Inoue, Makoto;Ueda, Hiroshi
在本研究中，我们首先报告了小鼠电刺激诱导爪屈曲（EPF）测试中三种不同正弦波刺激诱导的屈肌反应的体内特征。对小鼠后爪进行 5 Hz（C 纤维）、250 Hz（A δ 纤维）和 2000 Hz（A β 纤维）的固定正弦波电刺激可诱导爪弯曲反应和发声。正弦波刺激引起的爪屈肌反应的平均阈值远低于发声的平均阈值。新生儿（P3）用辣椒素预处理以退化多峰物质 P 能 C 纤维神经元，将阈值增加到 5 Hz（C 纤维）刺激，但没有增加到 250 Hz（Ad 纤维）和 2000 Hz（A β 纤维）。分别用 CP-99994 和 MK-801（NKI 和 NMDA 受体拮抗剂）进行鞘内 (i.t) 预处理，可显着阻断屈肌对 5 Hz 刺激的反应，但 CNQX（AMPA/红藻氨酸受体拮抗剂）则不会。另一方面，250 Hz 刺激引起的屈肌反应被 MK-801 (i. t.) 阻断，但不被 CP-99994 或 CNQX 阻断。相比之下，2000 Hz 刺激引起的屈肌反应仅被 CNQX 治疗阻断。这些数据表明我们已经确定了通过不同初级传入纤维介导的三种药理学不同类别的反应。此外，我们还利用 EPF 测试对神经损伤小鼠的每种感觉纤维类型的体内功能敏感性进行了表征，发现对 250 Hz 和 2000 Hz 刺激的阈值均显着降低，而对 5 Hz 刺激的阈值显着升高。因此，我们发现小鼠神经损伤对特定感觉纤维介导的反应产生相反的影响。这些结果还表明 EPF 分析可用于评估动物疾病模型中感觉功能的可塑性。
In the present study, we first report an in vivo characterization of flexor responses induced by three distinct sine-wave stimuli in the electrical stimulation-induced paw flexion (EPF) test in mice. The fixed sine-wave electric stimulations of 5 Hz (C-fiber), 250 Hz (A delta-fiber) and 2000 Hz (A beta-fiber) to the hind paw of mice induced a paw-flexion response and vocalization. The average threshold for paw flexor responses by sine-wave stimulations was much lower than that for vocalization. Neonatally (P3) pretreatment with capsaicin to degenerate polymodal substance P-ergic C-fiber neurons increased the threshold to 5 Hz (C-fiber) stimuli, but not to 250 Hz (Ad-fiber) and 2000 Hz (A beta-fiber). The flexor responses to 5 Hz stimuli were significantly blocked by intrathecal (i.t.) pretreatment with both CP-99994 and MK-801, an NKI and NMDA receptor antagonist, respectively, but not by CNQX, an AMPA/kainate receptor antagonist. On the other hand, the flexor responses induced by 250 Hz stimuli were blocked by MK-801 (i. t.) but not by CP-99994 or CNQX. In contrast, flexor responses induced by 2000 Hz stimuli were only blocked by CNQX treatment. These data suggest that we have identified three pharmacologically different categories of responses mediated through different primary afferent fibers. Furthermore, we also carried out characterization of the in vivo functional sensitivity of each of the sensory fiber types in nerveinjured mice using the EPF test, and found that the threshold to both 250 Hz and 2000 Hz stimulations were markedly decreased, whereas the threshold to 5 Hz stimulations was significantly increased. Thus we found opposing effects on specific sensory fiber-mediated responses as a result of nerve injury in mice. These results also suggest that the EPF analysis is useful for the evaluation of plasticity in sensory functions in animal disease models.