神经病理性疼痛大鼠不同大小DRG神经元兴奋性分型的研究
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摘要
目的研究神经病理性疼痛状态下,不同大小背根神经节(DRG)神经元兴奋性分型的特点,探讨不同大小DRG神经元兴奋性分型与神经病理性疼痛的关系。方法将SD大鼠随机分成正常组(Control组)、假手术组(Sham组)和坐骨神经分支选择性损伤模型组(SNI组)。运用热和冷刺激实验观察大鼠疼痛行为学变化;运用膜片钳技术记录不同大小DRG神经元兴奋性分型变化。结果与Control组比较,SNI组大鼠热缩足潜伏期无改变,但冷刺激抬足时间增加(P<0.05);与Control组比较,SNI组大鼠DRG神经元的1型和2型细胞构成比增加,3型细胞构成比减少(P <0.05);在Control组内,与大细胞比较,中、小细胞3型细胞的构成比较低,而1型和2型细胞的构成比较高(P <0.05);在SNI组内,与大细胞比较,中细胞3型细胞构成比较低,1型和2型细胞构成比较高(P <0.05),而小细胞与大细胞的构成比差异无统计学意义(P>0.05)。结论不同大小的DRG神经元兴奋性分型的改变是产生神经病理性疼痛的机制之一。
Objective To study the type of excitatory of DRG neurons in rats with neuropathic pain. Methods SD rats were randomly divided into normal group, sham operation group and SNI model group. The pain behavior changes of rats were observed by heat and cold stimulation experiments. The patch clamp technique was used to record the changes of excitability types of DRG neurons in different size. Results Compared with the normal group,the cold stimulation time was significantly increased(P < 0.05), while no significant change in the thermal paw latency in SNI model group was observed. Compared with the normal group, ratio of type 1 and type 2 DRG neurons were increased while ratio of type 3 cells decreased in the model group(P < 0.05). Composition of medium and small cells was lowered than that of large cells in SNI group when compared with those in the normal group(P < 0.05). In the SNI model group, the type of medium cell type 3 cells was relatively lower while type 1 and 2 cells was relatively higher compared with large cells(P < 0.05). There was no significant difference in the ratio of small cells to large cells among groups(P > 0.05). Conclusions The changes in excitatory typing of dorsal root ganglion cells with different sizes are potentially the mechanisms of neuropathic pain.
Objective To study the type of excitatory of DRG neurons in rats with neuropathic pain. Methods SD rats were randomly divided into normal group, sham operation group and SNI model group. The pain behavior changes of rats were observed by heat and cold stimulation experiments. The patch clamp technique was used to record the changes of excitability types of DRG neurons in different size. Results Compared with the normal group,the cold stimulation time was significantly increased(P < 0.05), while no significant change in the thermal paw latency in SNI model group was observed. Compared with the normal group, ratio of type 1 and type 2 DRG neurons were increased while ratio of type 3 cells decreased in the model group(P < 0.05). Composition of medium and small cells was lowered than that of large cells in SNI group when compared with those in the normal group(P < 0.05). In the SNI model group, the type of medium cell type 3 cells was relatively lower while type 1 and 2 cells was relatively higher compared with large cells(P < 0.05). There was no significant difference in the ratio of small cells to large cells among groups(P > 0.05). Conclusions The changes in excitatory typing of dorsal root ganglion cells with different sizes are potentially the mechanisms of neuropathic pain.
引文
[1]HAANPAA M,ATTAL N,BACKONJA M,et al.NeuPSIGguidelines on neuropathic pain assessment[J].Pain,2011,152(1):14-27.
[2]DECOSTERD I,WOOLF C J.Spared nerve injury:an animal model of persistent peripheral neuropathic pain[J].Pain,2000,87(2):149-158.
[3]MA B J,LIU X M,HUANG X H,et al.Translocator protein agonist Ro5-4864 alleviates neuropathic pain and promotes remyelination in the sciatic nerve[J].Molecular Pain,2018,10.1177/1744806917748019.
[4]DING C P,GUO Y J,LI H N,et al.Red nucleus interleukin-6participates in the maintenance of neuropathic pain through JAK/STAT3 and ERK signaling pathways[J].Experimental Neurology,2018(300):212-221.
[5]FANG X,DJOUHRI L,MCMULLAN S,et al.Intense isolectin-B4binding in rat dorsal root ganglion neurons distinguishes C-fiber nociceptors with broad action potentials and high Nav1.9expression[J].Journal of Neuroscience,2006,26(27):7281-7292.
[6]ZHANG J,CAVANAUGH D J,NEMENOV M I,et al.The modality-specific contribution of peptidergic and non-peptidergic nociceptors is manifest at the level of dorsal horn nociresponsive neurons[J].Journal of Physiology,2013,591(4):1097-1110.
[7]XIE R G,CHU W G,HU S J,et al.Characterization of different types of excitability in large somatosensory neurons and its plastic changes in pathological pain states[J].International Journal of Molecular Sciences,2018,10.3390/ijms 19010161.
[8]RICHNER M,BJERRUM O J,NYKJAER A,et al.The spared nerve injury(SNI)model of induced mechanical allodynia in mice[J].Journal of Visualized Experiments,2011(54):57-66.
[9]张萌,陈沁怡,谭朝阳,等.PAR2和TMEM16A在神经病理性疼痛模型大鼠背根神经节上的表达及意义[J].实用医学杂志,2017(22):3702-3706.
[10]韩媛媛,黄征,王艳萍,等.氯离子转运体在神经病理性疼痛大鼠背根神经节上表达的研究[J].中国疼痛医学杂志,2016,22(8):583-590.
[11]NORCINI M,SIDERIS A,HERNANDEZ L A M,et al.An approach to identify microRNAs involved in neuropathic pain following a peripheral nerve injury[J].Frontiers in Neuroscience,2014,8(8):266.
[12]WANG L J,WANG Y,CHEN M J,et al.Effects of niflumic acid onγ-aminobutyric acid-induced currents in isolated dorsal root ganglion neurons of neuropathic pain rats[J].Experimental&Therapeutic Medicine,2017,14(2):1373-1380.
[13]YANG Y,SI J Q,FAN C,et al.Effects of ropivacaine on GABA-activated currents in isolated dorsal root ganglion neurons in rats[J].Chinese Journal of Applied Physiology,2013,29(3):263-266.
[14]芦碧含,张文雯,李丽,等.炎症痛模型大鼠背根神经节神经元动作电位改变[J].中国疼痛医学杂志,2015,21(9):658-661.
[15]TREEDE R D,JENSEN T S,CAMPBELL J N,et al.Neuropathic pain:redefinition and a grading system for clinical and research purposes[J].Neurology,2009,72(14):1282-1283.
[16]HODGKIN A L.The local electric changes associated with repetitive action in a non-medullated axon[J].The Journal of Physiology,1948,107(2):165-181.
[17]LI L,RUTLIN M,ABRAIRA V,et al.The functional organization of cutaneous low-threshold mechanosensory neurons[J].Cell,2011,147(7):1615-1627.
[18]MEYER R A,RINGKAMP M,CAMPBELL J N,et al.Peripheral mechanisms of cutaneous nociception[M].Wall and Melzack's Textbook of Pain,2006,DOI:10.1016/BO-443-07287-6/50006-0.
[19]LI C L,LI K C,WU D,et al.Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity[J].Cell Research,2016,26(1):83.
[20]KANG X J,CHI Y N,CHEN W,et al.Increased expression of CaV3.2 T-type calcium channels in damaged DRG neurons contributes to neuropathic pain in rats with spared nerve injury[J].Molecular Pain,2018,10.1177/1744806918765808.
[21]JIANG H,SHEN X,CHEN Z,et al.Nociceptive neuronal Fcgamma receptor I is involved in IgG immune complex induced pain in the rat[J].Brain Behavior&Immunity,2017,62(351):351-361.
[2]DECOSTERD I,WOOLF C J.Spared nerve injury:an animal model of persistent peripheral neuropathic pain[J].Pain,2000,87(2):149-158.
[3]MA B J,LIU X M,HUANG X H,et al.Translocator protein agonist Ro5-4864 alleviates neuropathic pain and promotes remyelination in the sciatic nerve[J].Molecular Pain,2018,10.1177/1744806917748019.
[4]DING C P,GUO Y J,LI H N,et al.Red nucleus interleukin-6participates in the maintenance of neuropathic pain through JAK/STAT3 and ERK signaling pathways[J].Experimental Neurology,2018(300):212-221.
[5]FANG X,DJOUHRI L,MCMULLAN S,et al.Intense isolectin-B4binding in rat dorsal root ganglion neurons distinguishes C-fiber nociceptors with broad action potentials and high Nav1.9expression[J].Journal of Neuroscience,2006,26(27):7281-7292.
[6]ZHANG J,CAVANAUGH D J,NEMENOV M I,et al.The modality-specific contribution of peptidergic and non-peptidergic nociceptors is manifest at the level of dorsal horn nociresponsive neurons[J].Journal of Physiology,2013,591(4):1097-1110.
[7]XIE R G,CHU W G,HU S J,et al.Characterization of different types of excitability in large somatosensory neurons and its plastic changes in pathological pain states[J].International Journal of Molecular Sciences,2018,10.3390/ijms 19010161.
[8]RICHNER M,BJERRUM O J,NYKJAER A,et al.The spared nerve injury(SNI)model of induced mechanical allodynia in mice[J].Journal of Visualized Experiments,2011(54):57-66.
[9]张萌,陈沁怡,谭朝阳,等.PAR2和TMEM16A在神经病理性疼痛模型大鼠背根神经节上的表达及意义[J].实用医学杂志,2017(22):3702-3706.
[10]韩媛媛,黄征,王艳萍,等.氯离子转运体在神经病理性疼痛大鼠背根神经节上表达的研究[J].中国疼痛医学杂志,2016,22(8):583-590.
[11]NORCINI M,SIDERIS A,HERNANDEZ L A M,et al.An approach to identify microRNAs involved in neuropathic pain following a peripheral nerve injury[J].Frontiers in Neuroscience,2014,8(8):266.
[12]WANG L J,WANG Y,CHEN M J,et al.Effects of niflumic acid onγ-aminobutyric acid-induced currents in isolated dorsal root ganglion neurons of neuropathic pain rats[J].Experimental&Therapeutic Medicine,2017,14(2):1373-1380.
[13]YANG Y,SI J Q,FAN C,et al.Effects of ropivacaine on GABA-activated currents in isolated dorsal root ganglion neurons in rats[J].Chinese Journal of Applied Physiology,2013,29(3):263-266.
[14]芦碧含,张文雯,李丽,等.炎症痛模型大鼠背根神经节神经元动作电位改变[J].中国疼痛医学杂志,2015,21(9):658-661.
[15]TREEDE R D,JENSEN T S,CAMPBELL J N,et al.Neuropathic pain:redefinition and a grading system for clinical and research purposes[J].Neurology,2009,72(14):1282-1283.
[16]HODGKIN A L.The local electric changes associated with repetitive action in a non-medullated axon[J].The Journal of Physiology,1948,107(2):165-181.
[17]LI L,RUTLIN M,ABRAIRA V,et al.The functional organization of cutaneous low-threshold mechanosensory neurons[J].Cell,2011,147(7):1615-1627.
[18]MEYER R A,RINGKAMP M,CAMPBELL J N,et al.Peripheral mechanisms of cutaneous nociception[M].Wall and Melzack's Textbook of Pain,2006,DOI:10.1016/BO-443-07287-6/50006-0.
[19]LI C L,LI K C,WU D,et al.Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity[J].Cell Research,2016,26(1):83.
[20]KANG X J,CHI Y N,CHEN W,et al.Increased expression of CaV3.2 T-type calcium channels in damaged DRG neurons contributes to neuropathic pain in rats with spared nerve injury[J].Molecular Pain,2018,10.1177/1744806918765808.
[21]JIANG H,SHEN X,CHEN Z,et al.Nociceptive neuronal Fcgamma receptor I is involved in IgG immune complex induced pain in the rat[J].Brain Behavior&Immunity,2017,62(351):351-361.