Shih Hsi-Chien, Kuan Yung-Hui, Shyu Bai-Chung
Neuroscience, Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan.
Pain. 2017 Jul;158(7):1302-1313. doi: 10.1097/j.pain.0000000000000915.
Approximately 7% to 10% of patients develop a chronic pain syndrome after stroke. This chronic pain condition is called central poststroke pain (CPSP). Recent studies have observed an abnormal increase in the secretion of brain-derived neurotrophic factor (BDNF) in spinal cord tissue after spinal cord injury. An animal model of CPSP was established by an intrathalamus injection of collagenase. Mechanical and thermal allodynia was induced after lesions of the thalamic ventral basal complex in rats. Four weeks after the injection, the number of neurons decreased, the number of astrocytes, microglia, and P2X4 receptors increased, and BDNF mRNA expression increased in the brain lesion area. Nociceptive activity in the medial thalamus (MT) and the coherence coefficient of spontaneous field potential oscillations in the anterior cingulate cortex were enhanced in CPSP animals, and these enhancements were blocked by an acute injection of TrkB-Fc and TrkB antagonist Tat Cyclotraxin-B. Instead of being inhibited by the γ-aminobutyric acid (GABA) system in normal rats, multiunit activity in the MT was enhanced after a microinjection of muscimol, a GABAA receptor agonist, in CPSP animals. After CPSP, BDNF expression was enhanced in the MT, whereas the expression of GABAA channels and the cotransporter KCC2 decreased in the same area. These findings suggest that neuronal plasticity in the MT that was induced by BDNF overexpression after the thalamic lesion was a key factor in CPSP.
约7%至10%的中风患者会发展为慢性疼痛综合征。这种慢性疼痛状况被称为中风后中枢性疼痛（CPSP）。最近的研究观察到脊髓损伤后脊髓组织中脑源性神经营养因子（BDNF）的分泌异常增加。通过丘脑内注射胶原酶建立了CPSP动物模型。大鼠丘脑腹侧基底复合体损伤后诱发机械性和热痛觉过敏。注射四周后，脑损伤区域神经元数量减少，星形胶质细胞、小胶质细胞和P2X4受体数量增加，BDNF mRNA表达增加。CPSP动物内侧丘脑（MT）的伤害性活动以及前扣带回皮质自发场电位振荡的相干系数增强，急性注射TrkB-Fc和TrkB拮抗剂Tat Cyclotraxin-B可阻断这些增强作用。在正常大鼠中，MT的多单位活动受γ-氨基丁酸（GABA）系统抑制，但在CPSP动物中微量注射GABAA受体激动剂蝇蕈醇后，MT的多单位活动增强。CPSP后，MT中BDNF表达增强，而同一区域GABAA通道和共转运体KCC2的表达降低。这些发现表明，丘脑损伤后BDNF过表达诱导的MT神经元可塑性是CPSP的关键因素。
