Hypersensitivity of Prelimbic Cortex Neurons Contributes to Aggravated Nociceptive Responses in Rats With Experience of Chronic Inflammatory Pain.
Hypersensitivity of Prelimbic Cortex Neurons Contributes to Aggravated Nociceptive Responses in Rats With Experience of Chronic Inflammatory Pain.
复制标题
边缘前皮层神经元的超敏反应导致患有慢性炎性疼痛的大鼠伤害性反应加剧
DOI：
10.3389/fnmol.2018.00085
复制
发表时间：
2018
影响因子：
4.8
通讯作者：
Wan Y
中科院分区：
文献类型：
--
作者：
Fan XC;Fu S;Liu FY;Cui S;Yi M;Wan Y
先前的慢性疼痛经历会导致人类和动物对即将到来的有害事件的反应增强，但其潜在机制仍不清楚。在本研究中，我们发现完全弗氏佐剂（CFA）诱导的慢性炎性疼痛的大鼠表现出加重的疼痛反应，后来福尔马林试验。在慢性炎性疼痛大鼠的前边缘皮层（PL）中观察到福尔马林攻击后神经元活化增强和磷酸化cAMP反应元件结合蛋白（CREB）增加，抑制PL神经元活动可逆转加重的疼痛。炎性疼痛的经验诱导持续p38丝裂原活化蛋白激酶（MAPK; p38），但不是细胞外调节蛋白激酶（ERK）或c-Jun N-末端激酶（JNK）在PL的过度磷酸化。抑制PL中p38磷酸化可逆转对福尔马林实验的伤害性反应，并下调PL中磷酸化CREB的表达。化学遗传学鉴定PL-中脑导水管周围灰质（PAG）而不是PL-延髓核（NAc）是诱导加重的福尔马林疼痛的关键通路。我们的研究结果表明，持续过度磷酸化的p38在PL的基础加重慢性炎症疼痛的大鼠的伤害性反应的经验。
Previous experience of chronic pain causes enhanced responses to upcoming noxious events in both humans and animals, but the underlying mechanisms remain unclear. In the present study, we found that rats with complete Freund’s adjuvant (CFA)-induced chronic inflammatory pain experience exhibited aggravated pain responses to later formalin test. Enhanced neuronal activation upon formalin assaults and increased phosphorylated cAMP-response element binding protein (CREB) were observed in the prelimbic cortex (PL) of rats with chronic inflammatory pain experience, and inhibiting PL neuronal activities reversed the aggravated pain. Inflammatory pain experience induced persistent p38 mitogen-activated protein kinase (MAPK; p38) but not extracellular regulated protein kinase (ERK) or c-Jun N-terminal kinase (JNK) hyperphosphorylation in the PL. Inhibiting the p38 phosphorylation in PL reversed the aggravated nociceptive responses to formalin test and down-regulated enhanced phosphorylated CREB in the PL. Chemogenetics identified PL–periaqueductal gray (PAG) but not PL–nucleus accumbens (NAc) as a key pathway in inducing the aggravated formalin pain. Our results demonstrate that persistent hyperphosphorylation of p38 in the PL underlies aggravated nociceptive responses in rats with chronic inflammatory pain experience.
登录
查看更多内容
影响因子：
3.7
作者：
Baliki MN;Mansour AR;Baria AT;Apkarian AV
通讯作者：
Apkarian AV
影响因子：
3.3
作者：
Gisquet-Verrier, P.;Delatour, B.
通讯作者：
Delatour, B.
影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R
影响因子：
5.8
作者：
Edelmayer, Rebecca M.;Brederson, Jill-Desiree;Bitner, Robert S.
通讯作者：
Bitner, Robert S.
影响因子：
2.5
作者：
Gao, Yong-Jing;Ji, Ru-Rong
通讯作者：
Ji, Ru-Rong