Pain & Neuroscience, Discovery Research Laboratories for Core Therapeutic Areas, Shionogi & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan.
Shionogi TechnoAdvance Research & Co., Ltd., 1-1 Futaba-cho, 3-chome, Toyonaka, Osaka 561-0825, Japan.
Brain Res. 2019 Jul 15;1715:35-40. doi: 10.1016/j.brainres.2019.03.019. Epub 2019 Mar 18.
The mechanisms underlying central post-stroke pain are not well understood and there is no satisfactory treatment. Here, in a rat model of stroke, we measured nociceptive threshold using current stimulation of primary afferent neurons in both hind paws. Male Wistar rats underwent middle cerebral artery occlusion (MCAO) for 50 min. Nociceptive thresholds for Aβ, Aδ and C fiber stimulation (at 2000, 250, and 5 Hz, respectively, using a Neurometer), and neurological deficits, were measured for 23 days after MCAO. Sensory thresholds in both hind paws were significantly lower in MCAO model rats than in control rats for 23 days after MCAO, with the greatest difference seen in Aδ fibers and the smallest in C fibers. Brain infarct area was measured histologically, and the correlation between neurological deficit and infarct size was examined. Neurological deficits were worse in animals with larger infarcts. Furthermore, correlations were observed between infarct size, neurological deficit, and sensory threshold of Aδ fibers 1 day after MCAO. These findings indicate that rats develop hyperalgesia after MCAO and that sensory abnormalities in Aδ fibers after cerebral ischemia may play an important role in post-stroke pain.
中风后中枢性疼痛的发病机制尚不清楚,也没有令人满意的治疗方法。在这里,我们在中风大鼠模型中通过测量后肢初级传入神经元的电流刺激来测量痛觉阈值。雄性 Wistar 大鼠进行大脑中动脉闭塞(MCAO)50 分钟。在 MCAO 后 23 天,使用 Neurometer 分别以 2000、250 和 5 Hz 的频率测量 Aβ、Aδ 和 C 纤维刺激的痛觉阈值和神经功能缺损。MCAO 模型大鼠的后肢痛觉阈值在 MCAO 后 23 天内均显著低于对照组大鼠,其中 Aδ 纤维差异最大,C 纤维差异最小。通过组织学测量脑梗死面积,并检查神经功能缺损与梗死面积之间的相关性。梗死面积较大的动物神经功能缺损更严重。此外,在 MCAO 后 1 天,还观察到梗死面积、神经功能缺损和 Aδ 纤维感觉阈值之间的相关性。这些发现表明,大鼠在 MCAO 后会出现痛觉过敏,并且脑缺血后 Aδ 纤维的感觉异常可能在中风后疼痛中起重要作用。