本文采用大鼠坐骨神经慢性压迫损伤引起的神经病理痛模型,研究脊髓背角细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)在外周神经损伤引起的神经病理疼痛发生中的作用。结果显示,单侧坐骨神经压迫性损伤后1天,大鼠损伤侧脊髓背角ERK的磷酸化(激活)水平显著上调,其下游转录因子cAMP反应原件结合蛋白(cAMP response element binding protein,CREB)在双侧脊髓背角的激活水平也同时上调,而此时由神经损伤引起的痛觉敏化行为尚未出现。神经损伤之前和损伤后早期鞘内给予促分裂原活化蛋白激酶激酶(mitogen-activated protein kinase kinase,MEK)的抑制剂U0126,可阻断和延迟坐骨神经损伤引起的触诱发痛和热痛觉过敏行为的发生。这些结果提示,脊髓背角ERK-CREB信号的激活参与外周神经损伤引起的神经病理疼痛的发生,对该信号通路的早期干预可能是控制神经病理性疼痛的重要手段。
Interleukin-33 （IL-33）, a newly recognized IL-1 family member, is expressed by various tissues and cells. Since it can combine with chromosomes, IL-33 is regarded as an intracellular transcription repressor. Upon proinflammatory stimulation, it is released as an extracellular cytokine to function as an alarmin to dangerous signals. The IL-33 receptor is a heterodimer complex composed of ST2 and the IL-1 receptor accessory protein, the latter being conserved in other IL-1 family members. The IL-33/ST2 signaling pathway plays critical roles in inflammatory and immune diseases, as well as in central nervous system （CNS） diseases. Recently, there has been an increasing focus on IL-33, particularly on its production and functions in the CNS. The present review mainly focuses on progress in research on IL-33, especially its roles in the CNS.
Objective To explore the role of the extracellular signal-regulated kinase （ERK）/cAMP response element binding protein （CREB） pathway in the induction of long-term potentiation （LTP） in the anterior cingulate cortex （ACC） that may be implicated in pain-related negative emotion. Methods LTP of field potential was recorded in ACC slice and the expressions of phospho-ERK （pERK） and phospho-CREB （pCREB） were examined using immunohistochemistry method. Results LTP could be induced stably in ACC slice by high frequency stimulation （2-train, 100 Hz, 1 s）, while APv （an antagonist of NMDA receptor） could block the induction of LTP in the ACC, indicating that LTP in this experiment was NMDA receptor-dependent. Bath application of PD98059 （50 μmol/L）, a selective MEK inhibitor, at 30 min before tetanic stimulation could completely block the induction of LTP. Moreover, the protein level of pERK in the ACC was transiently increased after LTP induction, starting at 5 rain and returning to basal at 1 h after tetanic stimulation. The protein level of pCREB was also increased after LTP induction. The up-regulation in pERK and pCREB expressions could be blocked by pretreatment of PD98059. Double immunostaining showed that after LTP induction, most pERK was co-localized with pCREB. Conclusion NMDA receptor and ERK-CREB pathway are necessary for the induction of LTP in rat ACC and may play important roles in pain emotion.
