Department of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Neuroscience. 2013 Apr 3;235:10-5. doi: 10.1016/j.neuroscience.2013.01.005. Epub 2013 Jan 11.
We demonstrated previously that the lysophosphatidic acid-1 (LPA1) receptor plays a crucial role in the initiation of peripheral nerve injury-induced neuropathic pain through the alternation of pain-related genes/proteins expression and demyelination. The present study revealed that mild cerebral ischemia by left transient middle cerebral artery occlusion (tMCAO) for 15min causes the hypersensitive responses (paw withdrawal) to the nociception by electrical stimuli to the paw by the use of Neurometer Current Perception Threshold/C (CPT/C). The hypersensitivity or neuropathic pain was only observed by the stimulation with 250 and 2000, but not 5Hz, which are the characterized sine-wave frequencies of Aδ-, Aβ- or C-fibers, respectively. The significant neuropathic pain was observed from day 2 through week 2 on the right paw after tMCAO, while there was slight but significant pain sensitivity on the left paw at day 7. The neuropathic pain on the contralateral side at week 2 after tMCAO was completely abolished in LPA1(-/-) mice. These results suggest that LPA1 receptor signaling plays key roles in the development of central neuropathic pain following cerebral ischemia as well as the peripheral neuropathic pain following partial sciatic nerve injury.
我们之前已经证明，溶血磷脂酸-1（LPA1）受体通过改变疼痛相关基因/蛋白的表达和脱髓鞘在周围神经损伤诱导的神经性疼痛的发生中起着关键作用。本研究表明，通过短暂性左大脑中动脉闭塞（tMCAO）缺血 15 分钟会导致对足部电刺激的痛觉超敏反应（足部回缩）。只有用 250Hz 和 2000Hz 的刺激，而不是 5Hz 的刺激才会引起超敏反应或神经性疼痛，这分别是 Aδ、Aβ或 C 纤维的特征正弦波频率。在 tMCAO 后右侧足部第 2 天至第 2 周观察到明显的神经性疼痛，而在 tMCAO 后第 7 天左侧足部则有轻微但明显的疼痛敏感性。在 tMCAO 后第 2 周对侧足部的神经性疼痛在 LPA1（-/-）小鼠中完全消失。这些结果表明，LPA1 受体信号在缺血性脑卒中和部分坐骨神经损伤后周围神经性疼痛的发生中以及在缺血性脑卒中后中枢神经性疼痛的发生中起着关键作用。
