Effects of a cannabinoid agonist on spinal nociceptive neurons in a rodent model of neuropathic pain.
Effects of a cannabinoid agonist on spinal nociceptive neurons in a rodent model of neuropathic pain.
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DOI：
10.1152/jn.00498.2006
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发表时间：
2006-12
影响因子：
2.5
通讯作者：
Cheng Liu;J. Michael Walker
中科院分区：
文献类型：
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作者：
Cheng Liu;J. Michael Walker
研究了合成大麻素WIN 55,212-2对脊髓宽动态范围（WDR）神经元热诱发放电的影响。在慢性收缩性损伤（CCI）大鼠和假手术对照的同侧脊髓背角中记录了58个WDR神经元（1个细胞/只）。与假手术对照相比，CCI大鼠记录的神经元表现出自发放电、有害热诱发反应和放电后放电的升高以及感受野大小的增加。WIN 55,212-2（0.0625, 0.125和0.25 mg/kg，静脉注射）剂量依赖性地抑制了神经损伤大鼠和对照大鼠的热诱发活动，并减少了背角WDR神经元的感受野区域，其中对CCI大鼠的抑制作用更大。在0.125 mg/kg iv剂量下，WIN 55,212-2可逆转神经损伤引起的痛觉过敏。静脉给药WIN 55,212-2的作用似乎是中央介导的，因为直接给药结扎神经并没有抑制CCI大鼠的热诱发神经元活动。用大麻素CB(1)受体拮抗剂SR141716A或AM251预处理，而用CB(2)拮抗剂SR144528预处理，可阻断其作用。这些结果为大麻素有效抑制神经损伤引起的异常感觉反应的报道提供了神经基础。
The effects of the synthetic cannabinoid WIN 55,212-2 on heat-evoked firing of spinal wide dynamic range (WDR) neurons were examined in a rodent model of neuropathic pain. Fifty-eight WDR neurons (1 cell/animal) were recorded from the ipsilateral spinal dorsal horns of rats with chronic constriction injury (CCI) and sham-operated controls. Relative to sham-operated controls, neurons recorded in CCI rats showed elevations in spontaneous firing, noxious heat-evoked responses, and afterdischarge firing as well as increases in receptive field size. WIN 55,212-2 (0.0625, 0.125, and 0.25 mg/kg, intravenous) dose-dependently suppressed heat-evoked activity and decreased the receptive field areas of dorsal horn WDR neurons in both nerve injured and control rats with a greater inhibition in CCI rats. At the dose of 0.125 mg/kg iv, WIN 55,212-2 reversed the hyperalgesia produced by nerve injury. The effect of intravenous administration of WIN 55,212-2 appears to be centrally mediated because administration of the drug directly to the ligated nerve did not suppress the heat-evoked neuronal activity in CCI rats. Pretreatment with the cannabinoid CB(1) receptor antagonists SR141716A or AM251, but not the CB(2) antagonist SR144528, blocked the effects. These results provide a neural basis for reports of potent suppression by cannabinoids of the abnormal sensory responses that result from nerve injury.