Bagdas Deniz, Sonat Fusun Ak, Hamurtekin Emre, Sonal Songul, Gurun Mine Sibel
Department of Pharmacology and Toxicology, Faculty of Medicine, Uludag University, Bursa, Turkey.
Behav Pharmacol. 2011 Sep;22(5-6):589-98. doi: 10.1097/FBP.0b013e32834a1efb.
This study was designed to test the effects of intracerebroventricularly (i.c.v.) administered CDP-choline (cytidine-5'-diphosphate-choline; citicoline) and its metabolites in rat models of inflammatory and neuropathic pain. The i.c.v. administration of CDP-choline (0.5, 1.0 and 2.0 µmol) produced a dose and time-dependent reversal of mechanical hyperalgesia in both carrageenan-induced inflammatory and chronic constriction injury-induced neuropathic pain models in rats. The antihyperalgesic effect of CDP-choline was similar to that observed with an equimolar dose of choline (1 µmol). The CDP-choline-induced antihyperalgesic effect was prevented by central administration of the neuronal high-affinity choline uptake inhibitor hemicholinium-3 (1 µg), the nonselective nicotinic receptor antagonist mecamylamine (50 µg), the α7-selective nicotinic ACh receptor antagonist, α-bungarotoxin (2 µg) and the γ-aminobutyric acid B receptor antagonist CGP-35348 (20 µg). In contrast, i.c.v. pretreatment with the nonselective opioid receptor antagonist naloxone (10 µg) only prevented the CDP-choline-induced antihyperalgesic effect in the neuropathic pain model while the nonselective muscarinic receptor antagonist atropine (10 µg) did not alter the antihyperalgesic effect in the two models. These results indicate that CDP-choline-elicited antihyperalgesic effect in different models of pain occurs through mechanisms that seem to involve an interaction with supraspinal α7-selective nicotinic ACh receptors, and γ-aminobutyric acid B receptors, whereas central opioid receptors have a role only in the neuropathic pain model.
本研究旨在测试脑室内（i.c.v.）注射胞二磷胆碱（胞苷-5'-二磷酸胆碱；西地磷胆碱）及其代谢产物在炎症性和神经性疼痛大鼠模型中的作用。在角叉菜胶诱导的炎症性疼痛和慢性缩窄性损伤诱导的神经性疼痛大鼠模型中，脑室内注射胞二磷胆碱（0.5、1.0和2.0 μmol）可产生剂量和时间依赖性的机械性痛觉过敏逆转。胞二磷胆碱的抗痛觉过敏作用与等摩尔剂量的胆碱（1 μmol）相似。神经元高亲和力胆碱摄取抑制剂半胱氨酸-3（1 μg）、非选择性烟碱受体拮抗剂美加明（50 μg）、α7选择性烟碱型乙酰胆碱受体拮抗剂α-银环蛇毒素（2 μg）和γ-氨基丁酸B受体拮抗剂CGP-35348（20 μg）的中枢给药可阻止胞二磷胆碱诱导的抗痛觉过敏作用。相比之下，非选择性阿片受体拮抗剂纳洛酮（10 μg）的脑室内预处理仅能阻止胞二磷胆碱在神经性疼痛模型中诱导的抗痛觉过敏作用，而非选择性毒蕈碱受体拮抗剂阿托品（10 μg）并未改变这两种模型中的抗痛觉过敏作用。这些结果表明，胞二磷胆碱在不同疼痛模型中引发的抗痛觉过敏作用似乎是通过与脊髓上的α7选择性烟碱型乙酰胆碱受体和γ-氨基丁酸B受体相互作用的机制实现的，而中枢阿片受体仅在神经性疼痛模型中起作用。
