Administration of endocannabinoids prevents a referred hyperalgesia associated with inflammation of the urinary bladder
Administration of endocannabinoids prevents a referred hyperalgesia associated with inflammation of the urinary bladder
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DOI：
10.1097/00000542-200103000-00023
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发表时间：
2001-03-01
期刊：
影响因子：
8.8
通讯作者：
Rice, ASC
中科院分区：
文献类型：
--
作者：
Farquhar-Smith, WP;Rice, ASC
背景：在松节油引起的大鼠膀胱炎症后，体表部位的痛觉过敏是内脏炎性疼痛的主要症状。作者检查了内源性大麻素anandamide和棕榈酰乙醇酰胺油与该模型相关的痛觉过敏的作用。方法50只雌性Wistar大鼠膀胱灌胃0.5 ml 50%松节油致炎症后，测量其对有害热刺激的基线肢体戒断潜伏期。在引入松节油之前立即施用10或25 mg/kg的大麻酰胺或棕榈酰乙醇酰胺或对照物，大麻素CB1和CB2受体的拮抗剂仅与较高剂量的内源性大麻素共同施用。去除松节油后2、4、6、8和24 h记录潜伏期。将前肢和后肢退缩潜伏期的差异随时间绘制，并比较曲线下的面积。结果：膀胱炎症与后肢的相对热痛觉过敏有关。阿南达胺和棕榈酰乙醇酰胺减弱了这一参考；在10和25 mg/kg剂量下，受体拮抗剂SR141716A降低了阿南胺的镇痛作用，而受体拮抗剂SR144528则没有。SR141716A与棕榈酰基草酰胺共给药不影响镇痛效果，但SR144528可降低其镇痛效果。结论：阿南达明（通过CB1受体）和棕榈酰乙醇酰胺（推测通过CB受体）以剂量依赖性的方式减轻了痛觉过敏。CB和CB受体的位置可以影响神经生长因子驱动的与膀胱炎症相关的痛觉过敏。这些数据表明大麻素是一种治疗膀胱疼痛的新方法，
Background: Referred hyperalgesia to a somatopically appropriate superficial site is a cardinal symptom of visceral inflammatory pain and has been demonstrated after turpentine-induced urinary bladder inflammation in the rat. The authors examined the effect of the endocannabinoids anandamide and palmitoylethanolamide oil the referred hyperalgesia associated with this model.Methods After measurement of baseline limb withdrawal latencies to a noxious heat stimulus, the bladders of 50 female Wistar rats mere inflamed by intravesical administration of 0.5 ml 50% turpentine. Ten or 25 mg/kg of anandamide or palmitoylethanolamide or vehicle were administered immediately before introduction of turpentine, Antagonists to both the cannabinoid CB1 and CB2 receptors mere coadministered with the higher dose of endocannabinoids. Latencies were recorded 2, 4, 6, 8, and 24 h after removal of turpentine. The difference between fore limb and hind limb withdrawal latencies was plotted against time, and areas under these curves were compared.Results: Inflammation of the urinary bladder was associated with a relative thermal hyperalgesia referred to the hind limb. Anandamide and palmitoylethanolamide attenuated this referred;hyperalgesia at doses of 10 and 25 mg/kg, The CB, receptor antagonist SR141716A reduced the antihyperalgesic effect of anandamide, but the CB, antagonist SR144528 did not. Coadministration of SR141716A with palmitoylethatlolamide did not affect the antihyperalgesic effect but was reduced by SR144528.Conclusions: Anandamide (via CB1 receptors) and palmitoylethanolamide (putatively via CB, receptors) attenuated a referred hyperalgesia in a dose-dependent fashion. CB, and CB, receptors are strategically situated to influence the nerve growth factor-driven referred hyperalgesia associated with inflammation of the urinary bladder. These data implicate cannabinoids as a novel treatment for vesical pain,