大鼠神经病理性疼痛模型的建立及其引起抑郁样状态伴失眠的机制

doi:10.13481/j.1671-587X.20230411

Abstract

Abstract:

Objective：To establish the rat model of depressive state complicated with insomnia caused by neuropathic pain， and to clarify the effect of chronic constrict injury（CCI） on the mood and sleep-wake behaviors of the rats. Methods Sixteen male SD rats were divided into sham operation group （n=8） and CCI group （n=8）， respectively. In CCI group， 4-0 silk thread was used to ligate the right sciatic nerve trunk of the rats， and the intensity was to maintain the blood supply of the sciatic nerve adventitia. In sham operation group， the sciatic nerve trunk of the rats was exposed and separated without ligation. The paw withdraw mechanical threshold （PWMT） of rats in two groups was measured weekly after operation to evaluate the pain threshold changes. Sucrose preference test was used to detect the percentages of sucrose preference of rats in two groups； tail suspension test was used to detect the immobility time in tail suspension of rats in two groups；open field test was used to detect the total distance of horizontal movement of rats in two groups；whether or not the depression-like behaviors of the rats existed were assessed；the implantable electro encepha logram/myoelectricity was used to analyze the sleep-wake behaviors of the rats. Results Compared with sham operation group， during 1－4 weeks after modeling， the PWMT and the percentage of sucrose preference of the rats in CCI group were significantly decreased（P<0.01）， the immobility time in tail suspension of the rats was increased （P<0.01）， and the total distance of horizontal movement of the rats was decreased （P<0.01）. Compared with sham operation group，during 2－4 weeks after modeling，the subjective night wake amount of the rats in model group was increased significantly （P<0.01），the non-rapid eye movement （NREM） sleep amount was decreased （P<0.01）， and the rapid eye movement （REM） sleep amount was increased （P<0.05 or P<0.01）.Compared with sham operation group，the subjective night cumulative amount of sleep-wake states and the REM sleep cumulative amount of the rats in CCI group were increased （P<0.05 or P<0.01），and the NREM sleep cumulative amount was decreased（P<0.01）. Conclusion The CCI rats have the depressive state complicated with insomnia，and these symptoms show a chronic trend and persist until the 4th week after modeling； this model can be used for observation of long-term effect and studying of related mechanism of the depressive state comlicated with insomia.

Key words: Neuropathic pain, Insomnia, Depression, Disease model，animal

CLC Number:

R338

Zhengnan JIANG,Yijia ZHANG,Zhen LIU,Yunfei CHEN. Construction of neuropathic pain model in rats and its mechanism of depressive state complicated with insomnia[J].Journal of Jilin University(Medicine Edition), 2023, 49(4): 905-912.

Figures/Tables 4

Tab.1

PWMT of rats in two groups at different time points"

Group	PWMT
Group	T₀	T₁	T₂	T₃	T₄
Sham operation	15.30 $±$ 4.85	15.77 $±$ 4.64	16.55 $±$ 3.76	16.46 $±$ 4.93	13.84 $±$ 4.79
CCI	16.92 $±$ 3.75	1.56 $±$ 0.68^*△	1.37 $±$ 0.24^*△	1.68 $±$ 0.85^*△	1.43 $±$ 0.42^*△

Tab.1

Tab.2

Percentages of sucrose preference, immobility time in tail suspension, and total distance of horizontal movement of rats in two groups at different time points (n=8，x±s）"

Group	Percentage of sucrose preference (η/%)
Group	T₀	T₁	T₂	T₃	T₄
Sham operation	78.73 $±$ 4.78	82.54 $±$ 4.77	80.38 $±$ 7.70	79.70 $±$ 5.81	80.86 $±$ 6.04
CCI	81.93 $±$ 10.66	70.58 $±$ 10.60^*	57.93 $±$ 9.31^*	53.70 $±$ 11.65^*	54.30 $±$ 12.21^*
Group	Immobility time in tail suspension (t/s)
Group	T₀	T₁	T₂	T₃	T₄
Sham operation	26.95 $±$ 4.79	29.44 $±$ 6.04	34.40 $±$ 9.13	35.00 $±$ 5.58	37.19 $±$ 4.39
CCI	30.31 $±$ 4.97	49.31 $±$ 7.60^*	54.52 $±$ 12.05^*	61.39 $±$ 10.89^*	60.54 $±$ 8.80^*
Group	Total distance of horizontal movement (l/cm)
Group	T₀	T₁	T₂	T₃	T₄
Sham operation	2 833.17 $±$ 384.10	2 446.77 $±$ 419.88	2 670.23 $±$ 345.02	2 723.38 $±$ 212.06	2 418.97 $±$ 282.40
CCI	3 156.96 $±$ 239.11	1 328.83 $±$ 349.89^*	1 410.87 $±$ 397.03^*	1 293.05 $±$ 432.08^*	1 139.77 $±$ 407.49^*

Tab.2

Fig. 1

Fig. 2

References 30

1	MORIN C M， INOUE Y， KUSHIDA C， et al. Endorsement of European guideline for the diagnosis and treatment of insomnia by the World Sleep Society［J］. Sleep Med， 2021， 81： 124-126.
2	LOVATO N， LACK L. Insomnia and mortality： a meta-analysis［J］. Sleep Med Rev， 2019， 43： 71-83.
3	LANCEL M， BOERSMA G J， KAMPHUIS J. Insomnia disorder and its reciprocal relation with psychopathology［J］. Curr Opin Psychol， 2021， 41： 34-39.
4	GEBARA M A， SIRIPONG N， DINAPOLI E A，et al. Effect of insomnia treatments on depression： a systematic review and meta-analysis［J］. Depress Anxiety， 2018， 35（8）： 717-731.
5	刘灿，黄会珍，赵洪庆，等. 复方柴金解郁片对抑郁症失眠大鼠脑内GABA受体表达的影响［J］. 中国药理学通报， 2021， 37（5）： 724-730.
6	胡雪松，陈黎跃，李世福，等. 慢性疼痛患者的失眠情况及影响因素［J］. 昆明医科大学学报， 2021， 42（2）： 118-123.
7	国笑，王瑜，李少源，等. 抑郁与慢性疼痛共病动物模型的研究进展［J］. 世界科学技术-中医药现代化， 2019， 21（4）： 689-695.
8	KHAN J， RAMADAN K， KORCZENIEWSKA O，et al.Interleukin-10 levels in rat models of nerve damage and neuropathic pain［J］. Neurosci Lett， 2015， 592： 99-106.
9	付聪. 针刺申脉、照海穴治疗慢性失眠的临床研究及对失眠大鼠中枢c-fos蛋白表达的影响［D］. 上海：上海中医药大学， 2019.
10	XIA LP， LUO H， MA Q， et al. GPR151 in nociceptors modulates neuropathic pain via regulating P2X3 function and microglial activation［J］.Brain， 2021，144（11）：3405-3420.
11	骆晓峰，李瑶，胡江，等. 栀子苷对实验性帕金森病大鼠睡眠障碍的调节作用及其机制［J］. 吉林大学学报（医学版）， 2020， 46（6）： 1177-1181.
12	IMLACH W L， BHOLA R F， MOHAMMADI S A， et al. Glycinergic dysfunction in a subpopulation of dorsal horn interneurons in a rat model of neuropathic pain［J］. Sci Rep， 2016， 6： 37104.
13	SHEN C K， CAO K R， CUI S N， et al. SiNiSan ameliorates depression-like behavior in rats by enhancing synaptic plasticity via the CaSR-PKC-ERK signaling pathway［J］. Biomed Pharmacother， 2020， 124： 109787.
14	谭丽博，于佳慧，郑骁洋，等. “神宁藏香”对失眠大鼠的行为学及GABA能系统通路的影响［J］. 世界科学技术-中医药现代化， 2020， 22（11）： 4060-4068.
15	李文涛，刘长红，周晓华，等. 下丘脑-垂体-肾上腺轴紊乱对脊髓损伤大鼠抑郁样行为的影响及其机制［J］. 吉林大学学报（医学版）， 2019， 45（6）： 1395-1400.
16	赵慧源，田诗琪，翟春影，等. 柴胡皂苷a对抑郁模型大鼠脑内神经递质及行为学的影响［J］. 中国医学创新， 2021， 18（34）： 28-32.
17	张欢，郭改艳，黄娜，等. 染色域Y样蛋白介导的组蛋白巴豆酰化与抑郁小鼠模型中NGF和炎症因子水平及神经功能紊乱的关系［J］. 现代生物医学进展， 2022， 22（13）： 2422-2426.
18	夏忠源，秦家骏，陈先震，等. 间断束缚和单次束缚对抑郁小鼠模型建立的影响［J］.同济大学学报（医学版），2021，42（3）： 299-305.
19	薛强，邹鲁宏，张雪娟，等. 海马小胶质细胞参与SNI大鼠抑郁样行为相关机制的初步探究［J］. 热带医学杂志， 2022， 22（10）： 1351-1355， 1462.
20	PŁOSKA A， CIEŚLIK P， SIEKIERZYCKA A， et al. Neurochemical changes underlying cognitive impairment in olfactory bulbectomized rats and the impact of the mGlu5-positive allosteric modulator CDPPB［J］. Brain Res， 2021， 1768： 147577.
21	NOLLET M， HICKS H， MCCARTHY A P， et al. REM sleep’s unique associations with corticosterone regulation， apoptotic pathways， and behavior in chronic stress in mice［J］.Proc Natl Acad Sci U S A，2019，116（7）：2733-2742.
22	WU Y E， LI Y D， LUO Y J， et al. Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice［J］. Acta Pharmacol Sin， 2015， 36（11）： 1308-1317.
23	王叶情，王宇红，黄会珍，等. 复方柴金解郁方对抑郁症失眠大鼠海马、下丘脑CaMKⅡ和CREB表达影响及药效研究［J］.北京中医药大学学报，2021，44（5）：444-453.
24	李春艳，王宇红，王华，等. 抑郁合并失眠对大鼠HPA轴及下丘脑中氨基酸类和单胺类神经递质的影响［J］. 中国药理学通报， 2021， 37（6）： 815-822.
25	韩林勐. 酸枣仁的Magnoflorine与Spinosin联合用药发挥抗抑郁失眠作用机制的研究［D］. 天津：天津医科大学， 2020.
26	欧喜燕，李驰坤，李晓兵，等. 基于单味药-配伍的合欢花与酸枣仁水提取物对抑郁性失眠动物模型的影响［J］. 吉林中医药， 2019， 39（5）： 649-653.
27	龙清华. 郁证失眠的理论探讨及三草安神方对抑郁症失眠大鼠的干预作用［D］. 武汉：湖北中医药大学， 2017.
28	王韵桥. 逍遥散对肝郁证失眠大鼠模型海马mTOR信号通路的影响［D］. 南宁：广西中医药大学， 2019.
29	LI Y H， WANG Y M， XUAN C L， et al. Role of the lateral habenula in pain-associated depression［J］. Front Behav Neurosci， 2017， 11： 31.
30	CASPANI O， REITZ M C， CECI A， et al. Tramadol reduces anxiety-related and depression-associated behaviors presumably induced by pain in the chronic constriction injury model of neuropathic pain in rats［J］. Pharmacol Biochem Behav， 2014， 124： 290-296.

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Construction of neuropathic pain model in rats and its mechanism of depressive state complicated with insomnia

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