Strategy for spinal cord injury-induced pain

脊髓损伤引起的疼痛的策略

• 批准号: 13671599
• 负责人: KAWAMATA Mikito
• 金额: $ 2.5万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671599/
• 关键词: spinal cord injury; hyperalgesia; spinal dorsal norn; wide-dynamic-range neuron; high-threshold neuron

Background : Spinal cord injury(SCI) results in chronic central neuropathic pain in dermatomes caudal to the lesion(below-level pain) and rostral to the lesion(above-level pain), which has remained refractory to clinical, treatment despite the development of various therapeutic strategies. In order to gain a better understanding of the pain, we investigated changes in physiological and pharmacological properties of spinal dorsal horn neurons in spinal segments rostral and caudal to the lesion in rats with SCI.Methods : The right spinal cord of Sprague-Dawley rats was hemisected at the level of L2. At 10 to 14 days after the SCI, when mechanical hyperalgesia/allodynia had fully developed, spontaneous activity and evoked responses to non-noxious and noxious mechanical stimuli of wide-dynamic-range(WDR) and high-threshold(HT) neurons rostral and caudal to the lesion were recorded. Cumulative doses of morphine were administered systemically(0.1-3mg/kg) and spinally(0.1-5μg), and spontaneou … More s activity and evoked responses to the stimuli of the neurons were evaluated.Results : Spontaneous activity significantly increased in WDR neurons both rostral and caudal to the SCI site, but high-frequency background discharges with burst patterns were observed only in neurons rostral to the SCI site. After the SCI, which involved cutting the L2 dorsal root and hemisectioning the spinal cord, WDR and HT neurons rostral to the SCI site still had receptive fields on the skin of the hindpaw, dermatomes L3,L4 and L5. Significant increases in responses to the mechanical stimuli were seen both in WDR and HT neurons located both rostrally and caudally to the lesion. The responses to non-noxious and noxious stimuli were significantly greater in WDR neurons caudal to the SCI site than those in WDR neurons rostral to the SCI site. In contrast, the responses to noxious stimuli were significantly higher in HT neurons rostral to the SCI site than those in HT neurons caudal to the SCI site. Systemically administered morphine had a greater effect on responses to non-noxious and noxious stimuli of WDR neurons rostral to the SCI site than those caudal to the SCI site. Spinally administered morphine significantly suppressed responses of WDR neurons in SCI animals to non-noxious stimuli compared to those in sham-operated control animals.Conclusions : The findings suggest that changes in properties of spinal dorsal horn neurons after SCI are caused by different physiological and pharmacological mechanisms depending on the classification of the neurons and their segmental locations and that different spinal mechanisms contribute to SCI-induced pain. Less

背景：脊髓损伤（SCI）可导致皮节的慢性中枢神经性疼痛，发生在病变的尾侧（低水平疼痛）和吻侧（高水平疼痛），尽管发展了各种治疗策略，但临床治疗仍然难治性。为了更好地理解疼痛，我们研究了脊髓损伤大鼠脊髓节段吻侧和尾侧脊髓背角神经元的生理和药理学特性的变化。方法：取Sprague-Dawley大鼠右脊髓L2半切。在脊髓损伤后10至14天，当机械性痛觉过敏/异常性痛完全发展时，记录损伤侧吻侧和尾侧宽动态范围（WDR）和高阈值（HT）神经元对无害和有害机械刺激的自发活动和诱发反应。分别给药（0.1 ~ 3mg/kg）和（0.1 ~ 5μg），观察大鼠神经细胞的自发性活动和对刺激的反应。结果：脊髓损伤部位吻侧和尾侧的WDR神经元自发活动显著增加，但仅在脊髓损伤部位吻侧的神经元中观察到高频背景放电的爆发模式。脊髓损伤后，切断L2背根和脊髓半切，脊髓损伤部位吻侧的WDR和HT神经元在后爪、L3、L4和L5皮节皮肤上仍有接受野。对机械刺激的反应显著增加，在WDR和HT神经元均位于病变的眼侧和尾侧。脊髓损伤部位尾侧的WDR神经元对非有害和有害刺激的反应明显大于脊髓损伤部位吻侧的WDR神经元。相比之下，脑损伤部位吻侧的HT神经元对有害刺激的反应明显高于脑损伤部位尾侧的HT神经元。系统给药吗啡对脊髓损伤部位吻侧WDR神经元的非有害和有害刺激反应的影响大于脊髓损伤部位尾侧WDR神经元。与假手术对照动物相比，脊髓注射吗啡显著抑制脊髓损伤动物WDR神经元对非有害刺激的反应。结论：脊髓损伤后脊髓背角神经元性质的改变是由不同的生理和药理学机制引起的，这取决于神经元的分类和节段位置，不同的脊髓机制导致了脊髓损伤引起的疼痛。少

项目成果

Narimatsu E: "NMDA receptor-mediated mechanism of ketamine-induced facilitation of glutamatergic excitatory synaptic transmission"Brain Research. 953. 272-275 (2002)

Narimatsu E：“NMDA 受体介导的氯胺酮诱导的谷氨酸兴奋性突触传递促进机制”脑研究。

Kawamata M et al.: "Effects of halothane and isoflurane on hHyperexcitability of spinal dorsal horn neurons after incision in the rat"Anesthesiology. (in press). (2004)

Kawamata M 等人：“氟烷和异氟烷对大鼠切口后脊髓背角神经元超兴奋性的影响”麻醉学。

Koshizaki M, Kawamata M, Shimada SG, Saito Y, Collins JG: "5-HT3 receptors partially mediate halothane depression of spinal dorsal horn sensory neurons."Anesth Analg. 96(4). 1027-1031 (2003)

Koshizaki M、Kawamata M、Shimada SG、Saito Y、Collins JG：“5-HT3 受体部分介导脊髓背角感觉神经元的氟烷抑制。”Anesth Analg。

Kawamata T: "Involvement of capsaicin-sensitive fibers in spinal NMDA-indued glutamate rolease"Neuroreport. 12. 3447-3450 (2001)

Kawamata T：“辣椒素敏感纤维参与脊髓 NMDA 诱导的谷氨酸作用酶”Neuroreport。

Kwamata M et al.: "Effects of halothane and isoflurane on hHyperexcitability of spinal dorsal horn neurons after incision in the rat"Anesthesiology. (In press). (2004)

Kwamata M 等人：“氟烷和异氟烷对大鼠切口后脊髓背角神经元超兴奋性的影响”麻醉学。