Antinociceptive effect of cyclic phosphatidic acid and its derivative on animal models of acute and chronic pain.
Antinociceptive effect of cyclic phosphatidic acid and its derivative on animal models of acute and chronic pain.
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环磷脂酸及其衍生物对急慢性疼痛动物模型的镇痛作用。
DOI：
10.1186/1744-8069-7-33
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发表时间：
2011-05-14
期刊：
影响因子：
3.3
通讯作者：
Murakami-Murofushi K
中科院分区：
文献类型：
--
作者：
Kakiuchi Y;Nagai J;Gotoh M;Hotta H;Murofushi H;Ogawa T;Ueda H;Murakami-Murofushi K
环磷脂酸（cPA）是溶血磷脂酸（LPA）的结构类似物，但具有不同的生物学功能，如抑制LPA合成酶自分泌运动因子（ATX）。由于LPA是参与外周和中枢系统中的伤害感受的信号分子，因此预期cPA具有镇痛活性。我们表征了cPA和2-carb-cPA（2ccPA）（一种化学稳定的cPA类似物）对急性和慢性疼痛的影响。(1)全身注射2ccPA可显著抑制麻醉大鼠的躯体-心脏和躯体-躯体C反射，但对相应的A反射无明显影响。(2)2ccPA降低了敏感性，测量为通过C纤维对小鼠后爪施加的电刺激的缩爪反应，但不包括Aδ或Aβ。(3)在小鼠中，用2ccPA剂量依赖性地预处理抑制福尔马林诱导的舔和咬反应的第二阶段。(4)在小鼠中，用2ccPA预处理和重复后处理显著减弱了坐骨神经部分结扎后的热痛觉过敏和机械性异常性疼痛。(5)在大鼠中，用2ccPA重复后处理也显著减弱慢性坐骨神经收缩后的热痛觉过敏和机械性异常性疼痛。我们的研究结果表明，cPA及其稳定的类似物2ccPA抑制慢性和急性炎症诱导的C-纤维刺激，并且重复治疗后2ccPA的中枢作用减弱神经性疼痛。
Cyclic phosphatidic acid (cPA) is a structural analog of lysophosphatidic acid (LPA), but possesses different biological functions, such as the inhibition of autotaxin (ATX), an LPA-synthesizing enzyme. As LPA is a signaling molecule involved in nociception in the peripheral and central systems, cPA is expected to possess analgesic activity. We characterized the effects of cPA and 2-carba-cPA (2ccPA), a chemically stable cPA analog, on acute and chronic pain. (1) The systemic injection of 2ccPA significantly inhibited somato-cardiac and somato-somatic C-reflexes but not the corresponding A-reflexes in anesthetized rats. (2) 2ccPA reduced sensitivity measured as the paw withdrawal response to electrical stimulation applied to the hind paws of mice through the C-fiber, but not Aδ or Aβ. (3) In mice, pretreatment with 2ccPA dose-dependently inhibited the second phase of formalin-induced licking and biting responses. (4) In mice, pretreatment and repeated post-treatments with 2ccPA significantly attenuated thermal hyperalgesia and mechanical allodynia following partial ligation of the sciatic nerve. (5) In rats, repeated post-treatments with 2ccPA also significantly attenuated thermal hyperalgesia and mechanical allodynia following chronic sciatic nerve constriction. Our results suggest that cPA and its stable analog 2ccPA inhibit chronic and acute inflammation-induced C-fiber stimulation, and that the central effects of 2ccPA following repeated treatments attenuate neuropathic pain.
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影响因子：
2.5
作者：
McCall, WD;Tanner, KD;Levine, JD
通讯作者：
Levine, JD
影响因子：
5.7
作者：
Kissin, Igor;Freitas, Cristina F.;Bradley, Edwin L., Jr.
通讯作者：
Bradley, Edwin L., Jr.
DOI：
10.1016/s0169-328x(99)00333-2
发表时间：
2000-02-22
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Renbäck, K;Inoue, M;Ueda, H
通讯作者：
Ueda, H
影响因子：
1.8
作者：
KOBAYASHI, S;TOKUNOH, R;MURAKAMIMUROFUSHI, K
通讯作者：
MURAKAMIMUROFUSHI, K
影响因子：
4.8
作者：
Baker, Daniel L.;Fujiwara, Yuko;Tigyi, Gabor
通讯作者：
Tigyi, Gabor