title: SIP30 is required for neuropathic pain-evoked aversion in rats.
abstract: 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.
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China, and Department of Life Science, Fudan University, Shanghai 200433, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Han
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Ru-Yi
authors.initials: RY
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Zhao
authors.forename: Yu-Qiu
authors.initials: YQ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004195:Disease Models, Animal; D004644:Emotions / Q000502:physiology*; D006179:Gyrus Cinguli / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D017551:Microdialysis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism* / Q000523:psychology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D059467:Transcriptome
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D009419:Nerve Tissue Proteins; C459407:Zwint protein, rat
keywords: SIP30; anterior cingulate cortex; chronic constriction injury; neuropathic pain; pain-related negative emotion; place escape/avoidance paradigm