We profiled gene expression in the rat spinal cord and brain,and identified sip30 as a gene whose expression was elevated in a chronic constriction injury(CCI)model of neuropathic pain.Here we show that in the rostral anterior cingulate cortex(rACC),a key structure of pain affect,SIP30 increased in both sides after CCI.Inhibition of CCI-induced SIP30 upregulation by intra-rACC injection of shRNA targeting rat sip30 gene,neuropathic pain-evoked place escape/avoidance paradigm(PEAP),a behavioral test designed to quantify the level of negative emotion evoked by painful stimuli,was prevented.Interestingly,this blockade did not affect CCI-induced hyperalgesia and allodynia as well as general learning and memory.Consistently,intra-rACC PKA or ERK inhibitor suppressed CCI-induced SIP30 upregulation and blocked PEAP induction.Moreover,knocking down SIP30 robustly attenuated the frequency of miniature EPSCs(mEPSCs)in rACC slices and decreased extracellular glutamate concentration.All together,our results highlight the possibility that SIP30,as a PKA and ERK target,in the rACC mediated neuropathic pain-evoked negative emotion via modulating excitatory neurotransmitter release.