SIP30 Is Required for Neuropathic Pain-Evoked Aversion in Rats
SIP30 Is Required for Neuropathic Pain-Evoked Aversion in Rats
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SIP30 是大鼠神经性疼痛诱发厌恶所必需的
DOI：
10.1523/jneurosci.3160-13.2014
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发表时间：
2014-01-08
影响因子：
5.3
通讯作者：
Zhang, Yu-Qiu
中科院分区：
文献类型：
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作者：
Han, Mei;Xiao, Xiao;Zhang, Yu-Qiu
SIP30 （SNAP25相互作用蛋白30）是一个30 kDa的SNAP25相互作用蛋白，在神经递质释放中起作用。利用神经性疼痛慢性收缩损伤（CCI）模型，我们分析了大鼠脊髓和脑中的基因表达，并鉴定了CCI后sip30表达上调。在这里，我们发现CCI诱导了双侧吻侧前扣带皮层（rACC）中SIP30的增加，这是一个与疼痛有关的关键大脑区域。我们将大鼠放在一个一半涂成白色（浅色区），另一半涂成黑色（深色区）的房间里，并测量神经性疼痛诱发的地方逃避/回避范式（PEAP），以量化疼痛刺激引起的负面情绪水平。通过在racc内注射靶向大鼠SIP30基因的shRNA抑制cci介导的SIP30诱导，降低了PEAP。有趣的是，SIP30的敲低并不影响cci诱导的诱发性疼痛，如热痛觉过敏和机械异常性疼痛。它也不会影响一般的学习和记忆。cci诱导的SIP30上调与rACC中ERK、PKA和CREB的激活相关。在racc内给予PKA或ERK抑制剂可抑制cci诱导的SIP30上调并阻断PEAP的诱导。此外，SIP30的敲低抑制了mepsc的频率，增加了rACC切片中的成对脉冲比，降低了细胞外谷氨酸浓度。总之，我们的研究结果强调了SIP30作为rACC中PKA和ERK的靶点，通过调节谷氨酸释放和兴奋性突触传递来介导神经性疼痛诱发的负性情绪。
SIP30 (SNAP25 interacting protein of 30) is a SNAP25 interaction protein of 30 kDa that functions in neurotransmitter release. Using a chronic constriction injury (CCI) model of neuropathic pain, we profiled gene expression in the rat spinal cord and brain and identified sip30, which was upregulated after CCI. Here, we show that CCI induced a bilateral increase of SIP30 in the rostral anterior cingulate cortex (rACC), a key brain region that has been implicated in pain affect. We put rats in a chamber with one half painted white (light area) and the other half painted black (dark area), and measured neuropathic pain-evoked place escape/avoidance paradigm (PEAP) to quantify the level of negative emotion evoked by painful stimuli using a Von Frey hair. Inhibition of CCI-mediated induction of SIP30 by intra-rACC injection of shRNA targeting the rat sip30 gene reduced PEAP. Interestingly, knockdown of SIP30 did not affect CCI-induced evoked pain such as heat hyperalgesia and mechanical allodynia. Neither did it affect general learning and memory. CCI-induced upregulation of SIP30 was correlated with activation of ERK, PKA, and CREB in the rACC. Intra-rACC administration of PKA or ERK inhibitors suppressed CCI-induced SIP30 upregulation and blocked the induction of PEAP. Additionally, knockdown of SIP30 suppressed the frequency of mEPSCs and increased paired-pulse ratios in rACC slices and decreased extracellular glutamate concentrations. Together, our results highlight SIP30 as a target of PKA and ERK in the rACC to mediate neuropathic pain-evoked negative emotion via modulation of glutamate release and excitatory synaptic transmission.