Presynaptic cGMP-dependent protein kinase I(PKG-I) facilitates spinal synaptic plasticity and inflammatory pain
作者单位：Pharmakologisches InstitutUniversity HeidelbergIm Neuenheimer Feld 36669120 HeidelbergGermany
会议名称：《中国神经科学学会第四次会员代表大会暨第八届全国学术会议》
会议日期：2009年
学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学]
基 金：supported by a C.H.S.Prize and grants from the Deutsche Forschungsgemeinschaft (DFG) to R.K key NSFC grant(No.30530260) FMMU grant
关 键 词：PKG-I synaptic plasticity inflammatory pain LTP
摘 要：Objective Mechanisms underlying chronic,pathological pain are not *** in peripheral nociceptors and their synapses with spinal neurons can serve as a cellular basis for the development and maintenance of chronic pain following inflammation or nerve *** studies have shown that activation of nociceptive nerve afferents at frequencies relevant to pathological pain states can trigger a unique form of long-term potentiation(LTP) at spinal synapses between nociceptor terminals and spinal neurons projecting nociceptive information to the ***, relative pre- and post-synaptic contributions and underlying mechanisms of spinal LTP are not *** of the nitric oxide(NO)-cGMP-PKG-I pathway has been suggested in the induction of pathological pain in behavioural studies *** To address a potential presynaptic component to C-fiber-evoked LTP on spinal neurons,we generated mice conditionally lacking PKG-I,a key molecular target of cGMP,specifically in nociceptors(SNS-PKG-I mice).This led to absence of PKG-I in nociceptors,while preserving expression in spinal neurons,brain and all other organs.A combination of electrophysiological,behavioural and biochemical methods was used in the present study. Results We recorded homosynaptic LTP from spinal lamina I neurons projecting to the periaqueductal grey(PAG),which were visualized via retrograde labelling upon stereotactic injection of the fluorescent tracer DiI in the PAG.A conditioning low frequency stimulation of 2 Hz for 2 min(LFS) produced LTP of monosynaptic C-fiber-evoked EPSCs by more than 200%at 30 min in spinal-PAG projection neurons of control mice(PKG-Ifl/fl),but failed to do so in SNS-PKG-P’ mice.A protocol of minimal stimulation revealed that a decrease of frequency of synaptic failure was evoked following LFS conditioning stimulus in slices derived from PKG-Ifl/fl mice,while the rate of synaptic failure did not change significantly following LFS in slices