Kcnip3基因敲除对大鼠基础痛行为的影响
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摘要
目的:观察Kcnip3基因敲除对大鼠基础痛行为的影响,以进一步明确KChIP3(Kv4 channel interacting protein 3)分子在疼痛中的作用。方法:对野生型和Kcnip3基因敲除大鼠在基础状态下的痛行为反应和焦虑水平进行检测。结果:Kcnip3基因敲除大鼠与野生型大鼠相比,辐射热缩足潜伏期延长,50%机械缩足阈值升高,而热板实验中的舔足潜伏期和持续时长(30 s内),冷板实验中的抬足潜伏期和持续时长(1 min内),基因敲除大鼠和野生型大鼠相比无显著差异。高架十字迷宫实验中,Kcnip3基因敲除大鼠较野生型大鼠进入开放臂的次数减少,开放臂停留时间缩短。结论:Kcnip3基因敲除可降低基础状态下大鼠的反射性热痛和机械痛反应,而对非反射性痛行为无显著影响,这种差异可能与Kcnip3基因敲除导致大鼠处于高焦虑水平有关。
Objective: To observe the effects of Kcnip3 gene deletion on the basal pain behaviors in rats and further determine the role of KChIP3(Kv4 channel interacting protein 3) in pain modulation. Methods: We measured the pain behaviors of wild type, heterozygous and homozygous Kcnip3 gene deletion rats in the basal state, including the reflexive pain behaviors(plantar radiant heat test and von Frey test) and non-reflexive pain behaviors(hot plate test and cold plate test), and examined the anxiety levels using elevated plus maze test. Results: The heterozygous and homozygous Kcnip3 gene deletion rats showed prolonged paw withdrawal latency in the radiant heat test and elevated 50% paw withdrawal threshold compared to the wild type rats. However, there was no significant difference in the paw licking latency or licking duration(30 s) in the hot plate test and in the paw elevation latency or elevation duration(1 min) in the cold plate test between Kcnip3 gene deletion rats and wild type rats. The Kcnip3 gene deletion rats entered the open arms fewer times and spent less time in the open arms compared to the wild type rats. Conclusion: Kcnip3 gene deletion in rats alleviates the reflexive thermal pain and mechanical pain behaviors, but does not affect the non-reflexive pain behaviors in the basal state. The different responses to the reflexive and non-reflexive pain behavioral tests may be related to the high anxiety level caused by Kcnip3 gene deletion in rats.
Objective: To observe the effects of Kcnip3 gene deletion on the basal pain behaviors in rats and further determine the role of KChIP3(Kv4 channel interacting protein 3) in pain modulation. Methods: We measured the pain behaviors of wild type, heterozygous and homozygous Kcnip3 gene deletion rats in the basal state, including the reflexive pain behaviors(plantar radiant heat test and von Frey test) and non-reflexive pain behaviors(hot plate test and cold plate test), and examined the anxiety levels using elevated plus maze test. Results: The heterozygous and homozygous Kcnip3 gene deletion rats showed prolonged paw withdrawal latency in the radiant heat test and elevated 50% paw withdrawal threshold compared to the wild type rats. However, there was no significant difference in the paw licking latency or licking duration(30 s) in the hot plate test and in the paw elevation latency or elevation duration(1 min) in the cold plate test between Kcnip3 gene deletion rats and wild type rats. The Kcnip3 gene deletion rats entered the open arms fewer times and spent less time in the open arms compared to the wild type rats. Conclusion: Kcnip3 gene deletion in rats alleviates the reflexive thermal pain and mechanical pain behaviors, but does not affect the non-reflexive pain behaviors in the basal state. The different responses to the reflexive and non-reflexive pain behavioral tests may be related to the high anxiety level caused by Kcnip3 gene deletion in rats.
引文
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[14]Tiruppathi C,Soni D,Wang DM,et al.The transcription factor DREAM represses the deubiquitinase A20 and mediates inflammation.Nat Immunol,2014,15(3):239~247.
[15]Gomez-Villafuertes R,Torres B,Barrio J,et al.Downstream regulatory element antagonist modulator regulates Ca2+homeostasis and viability in cerebellar neurons.J Neurosci,2005,25(47):10822~10830.
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[17]Zhang Y,Su P,Liang P,et al.The DREAM protein negatively regulates the NMDA receptor through interaction with the NR1 subunit.J Neurosci,2010,30(22):7575~7586.
[18]Tian NX,Xu Y,Yang JY,et al.KCh IP3 N-Terminal 31-50 Fragment Mediates Its Association with TRPV1 and Alleviates Inflammatory Hyperalgesia in Rats.J Neurosci,2018,38(7):1756~1773.
[19]Gregory NS,Harris AL,Robinson CR,et al.An overview of animal models of pain:disease models and outcome measures.J Pain,2013,14(11):1255~1269.
[20]Bushnell MC,Ceko M,Low LA.Cognitive and emotional control of pain and its disruption in chronic pain.Nat Rev Neurosci,2013,14(7):502~511.
[2]Cheng HY,Pitcher GM,Laviolette SR,et al.DREAM is a critical transcriptional repressor for pain modulation.Cell,2002,108(1):31~43.
[3]Rivera-Arconada I,Benedet T,Roza C,et al.DREAM regulates BDNF-dependent spinal sensitization.Mol Pain,2010,6:95.
[4]Wu LJ,Mellstrom B,Wang H,et al.DREAM(downstream regulatory element antagonist modulator)contributes to synaptic depression and contextual fear memory.Mol Brain,2010,3:3.
[5]Benedet T,Gonzalez P,Oliveros JC,et al.Transcriptional repressor DREAM regulates trigeminal noxious perception.J Neurochem,2017,141(4):544~552.
[6]Chaplan SR,Bach FW,Pogrel JW,et al.Quantitative assessment of tactile allodynia in the rat paw.J Neurosci Methods,1994,53(1):55~63.
[7]Fontan-Lozano A,Romero-Granados R,del-Pozo-Martin Y,et al.Lack of DREAM protein enhances learning and memory and slows brain aging.Curr Biol,2009,19(1):54~60.
[8]Tunur T,Stelly CE,Schrader LA.DREAM/calsenilin/KCh IP3 modulates strategy selection and estradiol-dependent learning and memory.Learn Mem,2013,20(12):686~694.
[9]Mellstrom B,Sahun I,Ruiz-Nuno A,et al.DREAM controls the on/off switch of specific activity-dependent transcription pathways.Mol Cell Biol,2014,34(5):877~887.
[10]Pongs O,Schwarz JR.Ancillary subunits associated with voltage-dependent K+channels.Physiol Rev,2010,90(2):755~796.
[11]Buxbaum JD,Choi EK,Luo Y,et al.Calsenilin:a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment.Nat Med,1998,4(10):1177~1181.
[12]Carrion AM,Link WA,Ledo F,et al.DREAM is a Ca2+-regulated transcriptional repressor.Nature,1999,398(6722):80~84.
[13]Burgoyne RD,Haynes LP.Understanding the physiological roles of the neuronal calcium sensor proteins.Mol Brain,2012,5(1):2.
[14]Tiruppathi C,Soni D,Wang DM,et al.The transcription factor DREAM represses the deubiquitinase A20 and mediates inflammation.Nat Immunol,2014,15(3):239~247.
[15]Gomez-Villafuertes R,Torres B,Barrio J,et al.Downstream regulatory element antagonist modulator regulates Ca2+homeostasis and viability in cerebellar neurons.J Neurosci,2005,25(47):10822~10830.
[16]Savignac M,Pintado B,Gutierrez-Adan A,et al.Transcriptional repressor DREAM regulates T-lymphocyte proliferation and cytokine gene expression.Embo J,2005,24(20):3555~3564.
[17]Zhang Y,Su P,Liang P,et al.The DREAM protein negatively regulates the NMDA receptor through interaction with the NR1 subunit.J Neurosci,2010,30(22):7575~7586.
[18]Tian NX,Xu Y,Yang JY,et al.KCh IP3 N-Terminal 31-50 Fragment Mediates Its Association with TRPV1 and Alleviates Inflammatory Hyperalgesia in Rats.J Neurosci,2018,38(7):1756~1773.
[19]Gregory NS,Harris AL,Robinson CR,et al.An overview of animal models of pain:disease models and outcome measures.J Pain,2013,14(11):1255~1269.
[20]Bushnell MC,Ceko M,Low LA.Cognitive and emotional control of pain and its disruption in chronic pain.Nat Rev Neurosci,2013,14(7):502~511.