Lowered response threshold and increased responsiveness to mechanical stimulation of cutaneous nociceptive fibers in streptozotocin-diabetic rat skin in vitro - correlates of mechanical allodynia and hyperalgesia observed in the early stage of diabetes

Lowered response threshold and increased responsiveness to mechanical stimulation of cutaneous nociceptive fibers in streptozotocin-diabetic rat skin in vitro - correlates of mechanical allodynia and hyperalgesia observed in the early stage of diabetes
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DOI:
10.1016/s0168-0102(02)00033-0
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发表时间:
2002-06-01
影响因子:
2.9
通讯作者:
Mizumura, K
Mizumura, K
中科院分区:
医学4区
文献类型:
--
作者:
Suzuki, Y;Sato, J;Mizumura, K

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链脲佐菌素(STZ)致糖尿病大鼠表现出异常性疼痛和痛觉过敏,因此,已被提供作为糖尿病神经病变疼痛的模型。然而,最近对这些大鼠的电生理学研究发现,C-纤维伤害感受器并不总是对von Frey毛的机械刺激过度兴奋,并且它们的反应阈值没有变化。在本研究中,我们使用大鼠皮肤隐神经在体外制剂,其中确定的单一C-多模态受体(CPRs)的感受野可以准确地刺激与伺服控制的机械刺激器。在STZ注射后7-19天,糖尿病大鼠的行为伤害性反应增加,对CPRs进行单纤维记录。在糖尿病制剂中,具有自发活动的单位的比例和这种活动的幅度增加。糖尿病大鼠CPRs对斜坡压力刺激的反应阈值显著降低,对阈上刺激的反应幅度显著增加。此外,对机械刺激的反应模式也改变为非适应型。这些发现表明,CPRs的变化有助于在糖尿病神经病变的早期阶段观察到的伤害性感受增强。(C)2002 Elsevier Science爱尔兰有限公司和日本神经科学学会。All rights reserved.
Rats rendered diabetic by streptozotocin (STZ) show allodynia and hyperalgesia and thus, have been offered as a model of pain in diabetic neuropathy. However, recent electrophysiological studies on these rats found that C-fiber nociceptors were not consistently hyperexcitable to mechanical stimulations by von Frey hairs and that there was no change in their response thresholds. In the present study, we used rat skin-saphenous nerve in vitro preparations, in which the receptive fields of identified single C-polymodal receptors (CPRs) can be accurately stimulated with a servo-controlled mechanical stimulator. Single fiber recordings from CPRs were performed in diabetic rats with an increased behavioral nociceptive response 7-19 days after STZ injection. The proportion of units with spontaneous activity and the magnitude of this activity increased in the diabetic preparations. The response thresholds of CPRs were significantly decreased with ramp-pressure stimulation and their response magnitude to the suprathreshold stimulation was significantly increased in diabetic rats. In addition, the response pattern to mechanical stimulation was also changed to a non-adapting type. These findings suggest that changes in CPRs contribute to the enhanced nociception observed in the early stage of diabetic neuropathy. (C) 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.