Upregulations of P2X3 and ASIC3 involve in hyperalgesia induced by cisplatin administration in rats
Upregulations of P2X3 and ASIC3 involve in hyperalgesia induced by cisplatin administration in rats
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DOI：
10.1016/j.pain.2010.03.005
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发表时间：
2010-05-01
期刊：
影响因子：
7.4
通讯作者：
Sugiura, Yasuo
中科院分区：
文献类型：
--
作者：
Hori, Kiyomi;Ozaki, Noriyuki;Sugiura, Yasuo
在顺铂诱导的周围神经病变的大鼠模型中，检测了感觉神经元中表达的离子通道在机械和热痛觉过敏中的作用。大鼠腹腔注射顺铂3 mg/kg，每周1次，连续5周。采用von Frey试验、针刺试验和足底试验检测皮肤的毒性敏感性。腓肠肌（GM）的Randall-Selitto测试和握力的测量来量化肌肉痛觉过敏。通过旋转杆测试评估协调/运动。在背根神经节（DRG）神经元和支配GM的肌传入神经元中检测TRPV 1、TRPV 2、P2 X（3）和ASIC 3等离子通道的表达。评估了针对P2 X（3）或ASIC的拮抗剂对行为反应的影响。在顺铂治疗的动物中观察到皮肤和肌肉的机械性痛觉过敏和异常性疼痛。所有背根节神经元中TRPV 2、P2 X（3）和ASIC 3的表达均增加。此外，P2 X（3）和ASIC 3在背根节的肌肉传入神经元中的表达也增加。针对P2 X（3，2/3）和ASICs的拮抗剂显示对顺铂给药诱导的皮肤和肌肉痛觉过敏的抑制作用。TRPV 2、P2 X（3）和ASIC 3的上调可能在顺铂诱导的机械性痛觉过敏中起重要作用。此外，顺铂治疗还诱导与P2 X（3）和ASIC 3上调相关的肌肉传入神经元的肌肉痛觉过敏。(C)2010年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
The role of ion channels expressed in sensory neurons on mechanical and thermal hyperalgesia was examined in a rat model of cisplatin-induced peripheral neuropathy. The rats were injected with 3 mg/kg of cisplatin intraperitoneally once per week for five consecutive weeks. The von Frey test, pin-prick test and plantar test were performed to examine any noxious sensitivity of the skin. The Randall-Selitto test of the gastrocnemius muscle (GM) and the measurement of grip forces were performed to quantify muscle hyperalgesia. Coordination/motor was assessed by Rota-rod testing. Expressions of the ion channels TRPV1, TRPV2, P2X(3) and ASIC3 were examined in dorsal root ganglion (DRG) neurons and the muscle afferent neurons innervating GM. Effects of antagonists against either P2X(3) or ASICs on behavioral responses were evaluated. Mechanical hyperalgesia and allodynia of both skin and muscle were observed in cisplatin-treated animals. Expressions of TRPV2, P2X(3), and ASIC3 increased in all DRG neurons. In addition, expressions of P2X(3) and ASIC3 also increased in muscle afferent neurons in DRGs. Antagonists against P2X(3,2/3) and ASICs showed a suppressive effect on both skin and muscle hyperalgesia induced by cisplatin administration. Upregulation of TRPV2, P2X(3), and ASIC3 may play important roles in the mechanical hyperalgesia induced by cisplatin. Furthermore, cisplatin treatment also induced muscle hyperalgesia in muscle afferent neurons in connection with the upregulation of P2X(3) and ASIC3. (C) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.