Alteration in sensitivity of ionotropic glutamate receptors and tachykinin receptors in spinal cord contribute to development and maintenance of nerve injury-evoked neuropathic pain
Alteration in sensitivity of ionotropic glutamate receptors and tachykinin receptors in spinal cord contribute to development and maintenance of nerve injury-evoked neuropathic pain
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DOI：
10.1016/j.neures.2006.04.015
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发表时间：
2006-09-01
影响因子：
2.9
通讯作者：
Yonehara, Norifumi
中科院分区：
文献类型：
--
作者：
Yoshimura, Masakazu;Yonehara, Norifumi
周围神经损伤引起的痛觉异常或痛觉过敏可能与脊髓水平神经递质的敏感性改变有关。为了阐明神经递质在周围神经损伤中的功能作用，我们使用了坐骨神经慢性压迫所致神经损伤的大鼠(CCI大鼠模型)，并评估了鞘内注射已知影响谷氨酸和速激肽受体的药物的效果。在假手术大鼠，NMDA受体激动剂NMDA和AMPA-激动剂RS-(5)-溴马豆素缩短了戒断潜伏期。非竞争性NMDA受体拮抗剂MK-801、竞争性NMDA受体拮抗剂AP-5和AMPA-Kinate受体拮抗剂NBQX延长戒断潜伏期。P物质(SP)使戒断潜伏期延长，但只是一过性的。NK1受体拮抗剂RP67580延长戒断潜伏期，而NK2受体拮抗剂SR48968无此作用。在CCI大鼠，RS-(5)-溴马豆素缩短了戒断潜伏期，但对NMDA无影响。NBQX可延长戒断潜伏期，而MK-801和AP-5对戒断潜伏期无明显影响。SP缩短了戒断潜伏期，RP67580和SR48968均延长了戒断潜伏期。这些结果表明，脊髓内离子型谷氨酸受体和速激肽受体敏感性的改变参与了神经损伤性神经病理性疼痛的发生和维持。(C)2006年爱思唯尔爱尔兰有限公司和日本神经科学学会。版权所有。
Allodynia or hyperalgesia induced by peripheral nerve injury may be involved in changes in the sensitivity of neurotransmitters at the spinal cord level. In order to clarify the functional role of neurotransmitters in peripheral nerve injury, we used rats with nerve injury induced by chronic constriction of the sciatic nerve (CCI rat model) and estimated the effects of the intrathecal injection of drugs known to affect glutamate and tachykinin receptors. In sham-operated rats, the NMDA receptor agonist NMDA and AMPA-kinate receptor agonist RS-(5)-bromowillardin reduced withdrawal latency. The non-competitive NMDA receptor antagonist MK-801, competitive NMDA receptor antagonist AP-5 and AMPA-kinate receptor antagonist NBQX increased withdrawal latency. Substance P (SP) increased the withdrawal latency but only transitorily. The NK1 receptor antagonist RP67580 increased withdrawal latency, but the NK2 receptor antagonist SR48968 did not show an effect. In CCI rats, RS-(5)-bromowillardin reduced withdrawal latency, but NMDA did not show an effect. NBQX increased withdrawal latency, while MK-801 and AP-5 showed little or no effect. SP reduced withdrawal latency, and both RP67580 and SR48968 increased it. These results indicate that the alteration in sensitivity of ionotropic glutamate receptors and tachykinin receptors in the spinal cord contribute to development and maintenance of nerve injury-evoked neuropathic pain. (c) 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.