Activation of spinal and supraspinal cannabinoid-1 receptors leads to antinociception in a rat model of neuropathic spinal cord injury pain.
Activation of spinal and supraspinal cannabinoid-1 receptors leads to antinociception in a rat model of neuropathic spinal cord injury pain.
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DOI：
10.1016/j.brainres.2011.07.031
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发表时间：
2011-09-15
期刊：
影响因子：
2.9
通讯作者：
Sagen J
中科院分区：
文献类型：
--
作者：
Hama A;Sagen J
中枢神经系统大麻素亚型-1 （CB1）受体的激活已被证明可以介导全身给药的CB受体激动剂的抗痛觉性和其他作用。内源性肽CB受体配体hemopressin （HE）先前在后爪炎症大鼠中显示出抗伤害性作用，没有表现出CB1受体介导的特征性副作用。本研究评估了鞘内（i.t）和脑室内（i.c.v）注射HE对神经性脊髓损伤（SCI）疼痛大鼠模型的影响。非亚型选择性CB受体激动剂WIN 55,212-2也被集中施用于脊髓损伤大鼠作为比较。急性压迫中胸脊髓4周后，大鼠后爪退缩阈值明显降低，表明神经性疼痛低于正常水平。WIN 55,212-2的中央管理显著提高了提取阈值，而HE没有。据报道，加压素在体外可阻断CB1受体，类似于CB1受体拮抗剂利莫那班。利莫那班预处理完全阻断了中央给药WIN 55,212-2的抗伤害感受作用，而HE预处理则没有。虽然数据证实脊髓损伤大鼠脊髓上或脊髓CB1受体的激活可导致显著的抗痛觉作用，但目前的数据不支持急性阻断中枢CB1受体的抗痛觉作用，这是HE推测的神经性脊髓损伤大鼠的抗痛觉机制。尽管这种机制在其他具有显著炎症成分的疼痛模型中可能有用，但目前的数据表明，CB1受体的激活需要改善神经性脊髓损伤疼痛。
Activation of CNS cannabinoid subtype-1 (CB1) receptors has been shown to mediate the antinociceptive and other effects of systemically administered CB receptor agonists. The endogenous peptide CB receptor ligand hemopressin (HE) has previously demonstrated an antinociceptive effect in rats with a hind paw inflammation, without exhibiting characteristic CB1 receptor-mediated side-effects. The current study evaluated the effect of intrathecal (i.t.) and intracerebroventricular (i.c.v.) injection of HE in a rat model of neuropathic spinal cord injury (SCI) pain. The non-subtype selective CB receptor agonist WIN 55,212-2 was also centrally administered in SCI rats as a comparator. Four weeks following an acute compression of the mid-thoracic spinal cord, rats displayed markedly decreased hind paw withdrawal thresholds, indicative of below-level neuropathic pain. Central administration of WIN 55,212-2 significantly increased withdrawal thresholds, whereas HE did not. Hemopressin has been reported to block CB1 receptors in vitro, similar to the CB1 receptor antagonist rimonabant. Pretreatment with rimonabant completely blocked the antinociceptive effect of centrally administered WIN 55,212-2, but pretreatment with HE did not. While the data confirm that activation of either supraspinal or spinal CB1 receptors leads to significant antinociception in SCI rats, the current data do not support an antinociceptive effect from an acute blockade of central CB1 receptors, HE’s putative antinociceptive mechanism, in neuropathic SCI rats. Although such a mechanism could be useful in other models of pain with a significant inflammatory component, the current data indicate that activation of CB1 receptors is needed to ameliorate neuropathic SCI pain.
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