Zhang Ping-An, Xu Qi-Ya, Xue Lu, Zheng Hang, Yan Jun, Xiao Ying, Xu Guang-Yin
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Laboratory of Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China.
The Second Affiliated Hospital of Soochow University, Suzhou, China.
CNS Neurosci Ther. 2017 Feb;23(2):145-154. doi: 10.1111/cns.12663. Epub 2016 Dec 15.
Insular cortex (IC) is involved in processing the information of pain. The aim of this study was to investigate roles and mechanisms of P2X7 receptors (P2X7Rs) in IC in development of visceral hypersensitivity of adult rats with neonatal maternal deprivation (NMD).
Visceral hypersensitivity was quantified by abdominal withdrawal reflex threshold to colorectal distension (CRD). Expression of P2X7Rs was determined by qPCR and Western blot. Synaptic transmission in IC was recorded by patch-clamp recording.
The expression of P2X7Rs and glutamatergic neurotransmission in IC was significantly increased in NMD rats when compared with age-matched controls. Application of BzATP (P2X7R agonist) enhanced the frequency of spontaneous excitatory postsynaptic currents (sEPSC) and miniature excitatory postsynaptic currents (mEPSC) in IC slices of control rats. Application of BBG (P2X7R antagonist) suppressed the frequencies of sEPSC and mEPSC in IC slices of NMD rats. Microinjection of BzATP into right IC significantly decreased CRD threshold in control rats while microinjection of BBG or A438079 into right IC greatly increased CRD threshold in NMD rats.
Data suggested that the enhanced activities of P2X7Rs in IC, likely through a presynaptic mechanism, contributed to visceral hypersensitivity of adult rats with NMD.
岛叶皮质（IC）参与疼痛信息的处理。本研究旨在探讨P2X7受体（P2X7Rs）在新生期母婴分离（NMD）成年大鼠内脏高敏性发展过程中在岛叶皮质的作用及机制。
通过对结直肠扩张（CRD）的腹部退缩反射阈值来量化内脏高敏性。采用qPCR和蛋白质免疫印迹法检测P2X7Rs的表达。通过膜片钳记录来记录岛叶皮质的突触传递。
与年龄匹配的对照组相比，NMD大鼠岛叶皮质中P2X7Rs的表达和谷氨酸能神经传递显著增加。应用BzATP（P2X7R激动剂）可增加对照组大鼠岛叶皮质切片中自发性兴奋性突触后电流（sEPSC）和微小兴奋性突触后电流（mEPSC）的频率。应用BBG（P2X7R拮抗剂）可抑制NMD大鼠岛叶皮质切片中sEPSC和mEPSC的频率。向右侧岛叶皮质微量注射BzATP可显著降低对照组大鼠的CRD阈值，而向右侧岛叶皮质微量注射BBG或A438079可显著提高NMD大鼠的CRD阈值。
数据表明，岛叶皮质中P2X7Rs活性增强，可能通过突触前机制，导致NMD成年大鼠出现内脏高敏性。
