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GABAB receptors are involved in ventrolateral orbital cortex-evoked antinociception in rats with neuropathic and inflammatory pain

GABAB receptors are involved in ventrolateral orbital cortex...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Yan ZHAO~2,Wen-Jin XU~1,Feng-Yi XU~1,Fu-Quan HUO~(1,*),Chun-Xia YAN~2,Jing-Shi TANG~1 1 Department of Physiology,2 Department of Forensic Medicine,Xi’an Jiaotong University School of Medicine,Xi’an, Shaanxi 710061,China

Objective Previous studies have shown that the ventrolateral orbital cortex(VLO)is part of the endogenous analgesic system,which consists of an ascending pathway from the spinal cord to the VLO through the thalamic nucleus submedius and a descending pathway to the spinal cord via the periaqueductal gray(PAG).And the GABAergic interneurons tonically depress this antinociceptive pathway via GABA *** present study examined the role of GABA receptor,an autoreceptor,in the VLO-evoked antinociception in rats with neuropathic pain and inflammatory *** The paw withdrawal threshold(PWT)was measured for 60-min in response to mechanical stimulation(von Frey hairs)using the up-down method in a 10-min interval in spared nerve injury(SNI) rats,and the number of flinches and the durations of licking/biting of the affected paw during each 5-min period were record for 60-min as well as the expression of Fos in the spinal dorsal horn was counted by two experimenters blind to the different groups in formalin test ***(1)Microinjection of baclofen(0.5,1,2μg/0.5μL),a GABA receptor agonist,into the VLO attenuated the SNI-induced mechanical allodynia in a dose-dependent *** effect was completely blocked by the GABA receptor antagonist CGP35348(2.5μg/0.5μL).(2)Microinjection of baclofen(2μg/0.5μL)into the VLO also decreased the formalin-induced nociceptive behavior and the expression of Fos in the spinal dorsal *** effects were also completely reversed by the CGP35348(2.5μg/0.5μL).(3) When CGP35348 was injected alone into the VLO,there was no effect on the SNI-induced mechanical allodynia and formalin-induced nociceptive behavior as well as the expression of Fos in the spinal dorsal horn,suggesting that the blocking effects of CGP35348 on the baclofen-induced inhibition are not a result of facilitation of the nociceptive responses *** GABA receptors are involved in the VLO-evoked antinociception in rats with neuropathic and inflammatory

关键词： GABAB receptor neuropathic pain inflammatory pain ventrolateral orbital cortex

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SIP30 in the ventrolateral orbital cortex contributes to affective pain in rat

SIP30 in the ventrolateral orbital cortex contributes to aff...

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中国神经科学学会第十二届全国学术会议

作者： Ru-Yi Huang Mei Han Zhi-Qi Zhao Hong Cao Yu-Qiu Zhang Institutes of Brain Science and State Key Laboratory of Medical Neurobiology Fudan University

Objective SIP30（SNAP25 interacting protein of 30）, interacting with SNAP25, is widely expressed in the mammal brain and plays a role in neural activities. Our previous studies demonstrated that SIP30 in the r ACC mediates neuropathic pain-evoked negative emotion via modulation of glutamate release and excitatory synaptic transmission. Here, using a chronic constriction injury（CCI） model of neuropathic pain, we aim to explore the role of SIP30 in the ventrolateral orbital cortex（VLO） in painrelated negative emotion. Methods Rats were performed 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. Results Bilateral excitotoxic（quinolinic acid 200 nmol/ml） lesions of the VLO significantly blocked the formation of pain-related emotion without influence on CCI-induced mechanical allodynia and heat hyperalgesia. CCI induced a bilateral increase of SIP30 in the VLO. Upregulated SIP30 is predominantly colocalized with Neu N, a neuronal marker, but not with GFAP, an astrocyte marker, or OX-42, a microglial marker. Inhibition of CCImediated induction of SIP30 by intra-VLO injection of sh RNA targeting the rat sip30 gene reduced affective pain in the PEAP test. Interestingly, knockdown of SIP30 did not affect CCI-induced evoked pain hyperalgesia. Neither did it affect general learning and memory. Conclusion The present study strongly suggests that SIP30 in the ventrolateral orbital cortex plays an important role in neuropathic pain-evoked aversion.

关键词： ventrolateral orbital cortex neuropathic pain affective pain SIP30

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Sex differentiation of effect of microinjection of somatostatin into ventrolateral orbital cortex on formalin-induced nociceptive behavior in rats

Sex differentiation of effect of microinjection of somatosta...

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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

作者： Chao-Ling QU~(1,*),Bo XING~2,Yong-Hui DANG~2,Yan ZHAO~2,Feng-Yi XU~1,Fu-Quan HUO~1,Jing-Shi TANG~1 1 Department of Physiology and Pathophysiology,Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education,Xi’an Jiaotong University School of Medicine,Xi’an 710061,China 2 Department of Forensic Medicine,Key Laboratory of Environment and Gene Related to Diseases,Ministry of Education, Xi’an Jiaotong University School of Medicine,Xi’an 710061,China

Objective As a neuromodulator,somatostatin(SOM) and its receptors are involved in the antinociception in the spinal cord and the supraspinal ***,sex differences are observed in some pain-related *** studies have indicated that the ventrolateral orbital cortex(VLO) is involved in modulation of nociception as part of an endogenous analgesic system consisting of the spinal cord-nucleus submedius-VLO-periaqueductal gray-spinal cord *** aim of the current study was to examine whether the SOM and its receptors are involved in the VLO-induced antinociception in the rat formalin test,and determine whether there was a sex differentiation in the formalin *** After 5%formalin (50μl) was injected subcutaneously into the plantar surface of the hindpaw,the number of times of flinching the hindpaw per 5 min was measured as an index of nociceptive response to observe the effect of microinjection of SOM into the VLO on the nociceptive behavior in different sex *** SOM(10μg/0.5μl)microinjected into the VLO significantly decreased the number of the flinches in either early or later phases in the female rat,and this inhibitory effect was blocked by pre-treatment with its antagonist cyclo-somatostatin(c-SOM,25μg/0.5μl),whereas the SOM had no effect on the formalin-induced flinching behavior in the male ***,c-SOM microinjected alone into the VLO did not influence the flinching behavior in both male and female *** These results suggest that SOM and its receptors are involved in the antinociception in the VLO of the female,but not the male rats in the formalin test.

关键词： ventrolateral orbital cortex sex difference octreotide cyclo-somatostatin formalin test Flinching rat

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D2- like but not D1- like dopamine receptors in ventrolateral orbital cortex are involved in apomorphine-induced antiallodynia in a neuropathic pain model of rats

D2- like but not D1- like dopamine receptors in ventrolatera...

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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

作者： Yong-Hui DANG~1,Yan ZHAO~1,Bo XING~1,Xiao-Jie ZHAO~1,Teng CHEN~1,Jing-Shi TANG~2,Fu-Quan HUO~2,Feng-Yi XU~2, Chao-LingQU~(2,*) 1 Department of Forensic Medicine,Key Laboratory of Environment and Gene Related to Diseases,Ministry of Education, Xi''an Jiaotong University School of Medicine,Xi''an 710061,China 2 Department of Physiology and Pathophysiology,Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education,Xi''an Jiaotong University School of Medicine,Xi''an 710061,China

＜正＞Objective The ventrolateral orbital cortex（VLO） is part of an endogenous analgesic system consisting of an ascending pathway from the spinal cord to VLO via the thalamic nucleus submedius（Sm） and a descending pathway to the spinal cord relaying in the periaqueductal gray（PAG）.The aim of the present study was to examine whether dopamine and its receptors are involved in the antinociception in *** The animal model of persistent peripheral neuropathic pain-spared nerve injury（SNI） was *** withdrawal threshold in response to von-Frey hair stimulation of the injury side hindpaw was measured as an index of mechanical ***（1） Microinjection of the nonselective dopamine receptor agonist apomorphine（1.0,2.5,5.0μg in 0.5μl） into the VLO significantly increased the paw withdrawal threshold in a dose-dependent manner,which was reversed by pretreatment with selective D2-like dopamine receptor antagonist raclopride（1.5μg in 0.5μl）,but not selective D1-like dopamine receptor antagonist（SCH23390 5.0μg in 0.5μl）.（2） Microinjection of raclopride or SCH23390 alone into the VLO had no effects on mechanical paw withdrawal threshold. Conclusion The results suggest that dopamine neurotransmitter is involved in VLO-induced anti-allodynia,and this effect is mediated by D2-like but not Dl-like dopamine receptors.

关键词： ventrolateral orbital cortex dopamine receptor raclopride SCH23390 mechanical allodynia spared nerve injury rat

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5-HT2 receptor mediated antinociception in the ventrolateral orbital cortex:A possible pre-synaptic facilitatory effect

5-HT2 receptor mediated antinociception in the ventrolateral...

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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

作者： Hai-Yan SHENG,Fu-Quan HUO~*,Chao-Ling QU,Jing-Shi TANG Department of Physiology and Pathophysiology,Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education,Xi''an Jiaotong University School of Medicine,Xi''an 710061,China

＜正＞Objective Behavioral study has shown that 5-HT2 receptor was involved in the VLO-mediated descending *** 5-HT2 receptor is an excitatory G-protein-coupled receptor and is distributed not only in the postsynaptic neurons,but also in pre-synaptic neurons or ***,we suppose that activation of 5-HT2 receptor induced antinociception in VLO may be produced,except for by post-synaptic activation of the VLO neurons projecting to PAG,also probably through a pre-synaptic facilitatory effect on the excitatory synapse *** provide support for this hypothesis,the current study was designed to examine whether 5-HT2 receptor activation-induced antinociception could be blocked by glutamate receptor antagonist and enhanced by its *** radiant heatevoked tail flick（TF） reflex was used as an index of nociceptive *** effect of microinjection of drugs into the VLO on the TF reflex was *** Microinjection of DOI（4,8,16 nmol）,a 5-HT2 receptor agonist,into VLO depressed the TF reflex in a dose-dependent manner（r=0.999,P=0.008,y=5.351+3.534x）,and this inhibitory effect was significantly attenuated,but not completely blocked,by pre-microinjection of a non-selective glutamate receptor antagonist KA into VLO.A small dose（100 nmol） of glutamate administered into the VLO significantly enhanced the DOI-induced *** of KA alone into VLO did not change the baseline of TF *** These results provide support for above-mentioned hypothesis that 5-HT2 receptor activation-induced antinociception in VLO is produced at least partially through a pre-synaptic facilitatory effect on excitatory synapse transmission leading to activation of the VLO-PAG brainstem descending inhibitory system and depression of the nociceptive inputs at the spinal level.

关键词： antinocieption 5-HT2 receptor glutamate ventrolateral orbital cortex

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The relationship of serotoninergic terminals and GABAergic neurons in the ventrolateral orbital cortex of the rat:a light and electron microscopic study

The relationship of serotoninergic terminals and GABAergic n...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Fu-Quan HUO~(1*),Tao CHEN~(2*),Jing WANG~1,Yun-Qing LI~2,Jing-Shi TANG~1 1 Department of Physiology and Pathophysiology,Xi''an Jiaotong University School of Medicine,Key Laboratory of Environment and Genes Related to Diseases,Ministry of Education,Xi''an 710061 2 Department of Anatomy and K.K.Leung Brain Research Centre,The Fourth Military Medical University,Xi''an 710032

＜正＞Previous studies have indicated that the ventrolateral orbital cortex（VLO） is involved in an endogenous analgesic system consisting of the spinal cord-nucleus submedius -VLO-periaqueductal gray -spinal cord *** evidence showed serotonin（5-HT） ergic neurons in the dorsal raphe nucleuss（DR） sent their axons to the VLO and behavioral study results indicated GABAergic modulation is involved in the VLO 5-HT1 A receptor activation-induced *** current study examined the relationship of 5-HTergic terminals and GABAergic neurons in the rat’s VLO by using anterogradely labeled bind with immunofluorescence histochemical and immunoelectron microscopic method. The results showed that 5-HT-like immunoreactive（5-HT-ir） terminals and 5-HTl A receptor-like immunoreactive（5-HT1 A R-ir） neuronal cell bodies and terminals were distributed sparsely throughout layersⅡ-Ⅳof the VLO;The 5-HT-ir terminals were closely connected with GABA-like immunoreactive（GABA-ir） neurons;The majority of GABA-ir neurons express 5- HT1A R-ir and 5-HT-ir terminals made symmetrical synapses with GABA-ir *** results provide morphological evidences for GABAergic neurons involved in 5-HT1 A receptor activation-induced antinociception at the cortex level.

关键词： 5-HT 5-HT1A receptor GABAergic neuron ventrolateral orbital cortex immunofluorescence histochemical immunoelectron microscopy

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μ-opioid presynaptic inhibition of GABA release in rat ventrolateral orbital cortex neurons

μ-opioid presynaptic inhibition of GABA release in rat vent...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Chao-Ling QU~1,Fu-Quan HUO~1,Fen-Sheng HUANG~1,Yun-Qing LI~2,Jing-Shi TANG~1 1 Department of Physiology and Pathophysiology,Xi''an Jiaotong University School of Medicine,Key Laboratory of Environment and Genes Related to Diseases,Ministry of Education,Xi''an 710061 2 Department of Anatomy and K.K.Leung Brain Research Centre,The Fourth Military Medical University,Xi''an 710032

＜正＞Previous studies have indicated that the ventrolateral orbital cortex（VLO） is involved in modulation of nociception as part of an endogenous analgesic system consisting of the spinal cord-nucleus submedius（Sm）-VLO-periaqueductal gray（PAG）-spinal cord *** of morphine into the VLO depresses the rat tail-flick reflex and suggests that the GABAergic modulation may be involved in the VLO morphine-induced *** provide electrophysiological evidence for the GABAergic modulation mechanism,the present study examined whether the presynapticμ-opioid activation inhibited release of the GAB A neurotransmitter in rat VLO *** TTX,a voltage-dependent Na+ channel blocker and kynurentic acid,a non-selective excitatory amino acid receptor antagonist,pharmacologically separated spontaneous GABAergic miniature inhibitory postsynaptic currents（mIPSCs） were recorded using the whole-cell patch clamp *** results showed that DAMGO,a specificμ-opioid receptor agonist,inhibited mlPSCs frequency in a dose-dependent manner without affecting mIPSC amplitude in the same VLO *** presynaptic opioid effect was blocked by CTOP,a specificμ-opioid receptor *** alone application did not affect the mIPSC amplitude or *** results provide support for the hypotheses that GABAergic modulation is involved in the opioidinduced antinociception,i.e.,theμ-opioid receptor activation presynaptically inhibits the inhibitory effect of GABAergic neurons on the projection neurons leading to activation of the VLO-PAG brainstem descending inhibitory system and depression of the nociceptive inputs at the spinal cord level.

关键词： ventrolateral orbital cortex mIPSCs DAMGO CTOP whole-cell patch clamp

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Modulation of pain by activating circuit of thalamic nucleus submediusventrolateral orbital cortex-periaqueductal gay

Modulation of pain by activating circuit of thalamic nucleus...

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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

作者： Jing-Shi TANG~*,Fu-Quan HUO,Chao-Ling QU Department of Physiology and Pathophysiology,Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education,Xi’an Jiaotong University School of Medicine,Xi’an 710061,China

In view of the anatomical and electrophysiological studies,we propose that the thalamic submedius nucleus (Sm) and the ventrolateral orbital cortex(VLO) are involved in modulation of nociception such that activation of ascending nociceceptive pathway through Sm to VLO leads to activation of the periaqueductal gray(PAG) brainstem descending inhibitory system and depression of nociceptive inputs at the spinal and trigeminal *** provide support for this hypothesis,we carried out a series of experiments using animal behavioral,electrophysiological,neuropharmacological and immunohistochemical *** results are summarized as follows.(1).Bilateral electrolytic lesions or GABAinduced inhibition of Sm or VLO facilitated the rat tail-flick(TF) reflex(shortened TF latency) and eliminated the analgesia induced by high intensity(5 mA) electroacupuncture(EA) stimulation but not by low intensity(0.5 mA) EA stimulation as assessed by the TF test and the nociceptive responses of neurons in the spinal dorsal horn.(2).Electrically or chemically evoked-activation of Sm or VLO depressed the TF reflex,jaw-opening reflex and nociceptive responses of the spinal dorsal horn neurons,and that these antinociceptive effects were blocked by electrolytic lesions of or GABA-induced depression of VLO or PAG.(3).Microinjection of opioid agents into Sm or VLO depressed the TF reflex,formalin or bee venom-induced nociceptive behaviors and Fos expression in the spinal dorsal horn as well as the allodynia induced in a neuropathic pain model,and that these effects were antagonized byμ-opioid receptor antagonist,but not by 8- and K-opioid receptor *** morphine inhibited the activity of On-cells and excited the activity of Off-cells in Sm,the interaction of two classes of pain modulatory neurons may be the cellular mechanism of opioid-induced descending antinociception. (4).Microinjection of 5-HT receptor agonists into Sm or VLO depressed the TF reflex,formalin-induced nocicept

关键词： thalamic submedius nucleus ventrolateral orbital cortex periaqueductal gray nociceptive modulation opioid serotonin dopamine glutamate GABA

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