Spinal and peripheral analgesic effects of the CB2 cannabinoid receptor agonist AM1241 in two models of bone cancer-induced pain
Spinal and peripheral analgesic effects of the CB2 cannabinoid receptor agonist AM1241 in two models of bone cancer-induced pain
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DOI：
10.1111/j.1476-5381.2009.00629.x
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发表时间：
2010-06-01
影响因子：
7.3
通讯作者：
Baamonde, A.
中科院分区：
文献类型：
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作者：
Curto-Reyes, V.;Llames, S.;Baamonde, A.
背景和目的：在慢性疼痛的实验模型中，CB 2受体的激活诱导镇痛。本实验旨在研究外周或脊髓CB 2受体的激活是否减轻两种骨癌疼痛模型中的热痛觉过敏和机械异常性疼痛。实验方法：将NCTC 2472骨肉瘤或B16-F10黑色素瘤细胞胫骨内接种到C3 H/He和C57 BL/6小鼠。热痛觉过敏通过单侧热板试验进行评估，机械异常性疼痛通过von Frey试验进行评估。使用了AM 1241（CB 2受体激动剂）、AM 251（CB 1受体拮抗剂）、SR 144528（CB 2受体拮抗剂）和纳洛酮。关键结果：AM 1241（0.3-10 mg center dot kg-1）消除两种肿瘤模型中的热痛觉过敏和机械异常性疼痛。皮下、鞘内或肿瘤周围给予SR 144528可拮抗抗痛觉过敏作用。相比之下，全身或鞘内注射SR 144528可抑制抗异常性疼痛作用，但肿瘤周围注射无抑制作用。AM 1241的作用不受AM 251的影响，但被纳洛酮阻止。脊髓或背根神经节CB 2受体表达无明显变化。结论和意义：脊髓CB 2受体参与AM 1241在两种肿瘤模型中诱导的抗痛觉超敏作用，而外周和脊髓受体参与抗痛觉过敏作用。这两种作用均由内源性阿片类物质介导。使用激活CB 2受体的药物可能是抵消骨癌引起的疼痛症状的有用策略。
Background and purpose:The activation of CB2 receptors induces analgesia in experimental models of chronic pain. The present experiments were designed to study whether the activation of peripheral or spinal CB2 receptors relieves thermal hyperalgesia and mechanical allodynia in two models of bone cancer pain.Experimental approach:NCTC 2472 osteosarcoma or B16-F10 melanoma cells were intratibially inoculated to C3H/He and C57BL/6 mice. Thermal hyperalgesia was assessed by the unilateral hot plate test and mechanical allodynia by the von Frey test. AM1241 (CB2 receptor agonist), AM251 (CB1 receptor antagonist), SR144528 (CB2 receptor antagonist) and naloxone were used. CB2 receptor expression was measured by Western blot.Key results:AM1241 (0.3-10 mg center dot kg-1) abolished thermal hyperalgesia and mechanical allodynia in both tumour models. The antihyperalgesic effect was antagonized by subcutaneous, intrathecal or peri-tumour administration of SR144528. In contrast, the antiallodynic effect was inhibited by systemic or intrathecal, but not peri-tumour, injection of SR144528. The effects of AM1241 were unchanged by AM251 but were prevented by naloxone. No change in CB2 receptor expression was found in spinal cord or dorsal root ganglia.Conclusions and implications:Spinal CB2 receptors are involved in the antiallodynic effect induced by AM1241 in two neoplastic models while peripheral and spinal receptors participate in the antihyperalgesic effects. Both effects were mediated by endogenous opiates. The use of drugs that activate CB2 receptors could be a useful strategy to counteract bone cancer-induced pain symptoms.