Wutoutang Modulation Hippocampal BDNF/TrkB Pathway to Relieve Pain-emotion Co-curation

Hong-yan WU; Yu-qi SHI; Chun-yan ZHU; Na LIN

doi:10.13422/j.cnki.syfjx.20200136

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Wutoutang Modulation Hippocampal BDNF/TrkB Pathway to Relieve Pain-emotion Co-curation

Classic Prescriptions | 更新时间：2021-02-09

- Wutoutang Modulation Hippocampal BDNF/TrkB Pathway to Relieve Pain-emotion Co-curation
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 1, Pages: 24-30(2020)
- 作者机构：
  
  1.贵州中医药大学，贵阳　 550000
  2.中国中医科学院　中药研究所，北京　 100700
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20200136
  CLC： R2-0; R289; R285.5; R246.6
- Received：01 April 2019，
  
  Published Online：18 September 2019，
  
  Published：05 January 2020
- 稿件说明：
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Hong-yan WU, Yu-qi SHI, Chun-yan ZHU, et al. Wutoutang Modulation Hippocampal BDNF/TrkB Pathway to Relieve Pain-emotion Co-curation[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(1): 24-30.
DOI：

Hong-yan WU, Yu-qi SHI, Chun-yan ZHU, et al. Wutoutang Modulation Hippocampal BDNF/TrkB Pathway to Relieve Pain-emotion Co-curation[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(1): 24-30. DOI： 10.13422/j.cnki.syfjx.20200136.

摘要

目的：

探索乌头汤对海马组织内脑源性神经营养因子/原肌球蛋白受体激酶B(BDNF/TrkB)通路的调控作用，以明确乌头汤抑制神经病理性疼痛(NP)达到痛与情绪共治的初步机制。

方法：

将小鼠随机分为假手术组(sham)，脊神经结扎组(SNL)，乌头汤组(乌头汤)，乌头汤-ANA12拮抗剂组(乌头汤-ANA12)，普瑞巴林(PGB)组和盐酸氟西汀(FLU)组6组。所有小鼠针对海马安装给药套管，除假手术组暴露但不结扎神经外，其余组均进行脊神经结扎。术后1～21 d，各给药组分别以126 mg·kg

-1

乌头汤水煎液，25 mg·kg

-1

PGB，3 mg·kg

-1

FLU灌胃给药，sham组及SNL组以等体积生理盐水灌胃，1次/d。术后10～16 d进行海马套管给药，其中乌头汤-ANA12组给予TrkB受体拮抗剂ANA12(50 nmol·L

-1

)，其余组给予等体积生理盐水。采用Von Frey法检测小鼠的机械痛阈值，采用旷场和悬尾实验分别检测小鼠的焦虑和抑郁症状，采用高尔基染色法检测小鼠海马CA3区椎体神经元的病理性改变。

结果：

与假手术组比较，SNL模型组小鼠机械痛阈值显著降低，旷场中心区停留时间显著降低，悬尾不动时间显著增加(

0.01)，海马神经元树突分支数明显减少(

0.05，

0.01)；与SNL模型组比较，术后9～21 d乌头汤组小鼠的机械痛阈值显著增高，旷场中央区停留时间显著增高，悬尾不动时间显著降低，海马CA3区椎体神经元顶部和底部树突分支数显著增高(

0.01)；与SNL模型组比较，乌头汤-ANA12组的机械痛阈值在术后9 d显著增高(

0.01)，但在通过套管进行ANA12干预后，乌头汤-ANA12组的机械痛阈值持续降低，在术后14～21 d与SNL组比较无统计学差异。乌头汤-ANA12组小鼠中心场停留时间在术后9 d较SNL模型组显著增高(

0.01)，但在小鼠海马进行ANA12干预后，乌头汤-ANA12组的中心场停留时间持续降低，在术后21 d降至与SNL组无统计学差异；乌头汤-ANA12组小鼠悬尾不动时间在术后21 d与SNL组比较无统计学差异；海马高尔基染色显示，乌头汤-ANA12组海马CA3区椎体神经元顶部和底部树突分支数与SNL组比较无统计学差异。

结论：

乌头汤能缓解SNL导致的海马CA3区椎体神经元损伤及痛共情绪障碍症状，相关作用可能与其对海马BDNF/TrkB通路的调控有关。

Abstract

Objective:

To explore the mediating effect of Wutoutang (WTT) on brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) pathway in hippocampus and to clarify the mechanism of therapeutic action of WTD on pain-emotion comorbidity by inhibiting neuropathic pain (NP) preliminarily.

Method:

The mice were divided into sham group

spinal cord ligation (SNL) group

Wutoutang (WTT) group

Wutoutang-ANA12 antagonist (WTT-ANA12) group

pregabalin (PGB) group

Fluoxetine Hydrochloride (FLU) group randomly. Mice were fixed with the drug delivery cannula for hippocampal CA3.The L5 spinal cord of mice were tightly ligated but sham group (only exposed). During the 10-16

day after surgery

WTT

WTT-ANA12 groups were gavaged with 126 mg·kg

-1

WTT

PGB and FLU groups were respectively given 25 mg·kg

-1

PGB and 3 mg·kg

-1

FLU

sham and SNL groups were given the physiological saline once a day. Then

50 nmol·L

-1

ANA12 were given to the hippoicampal CA3 of the WTT-ANA12 mice by drug delivery cannula

and physiological saline were given to the others on the 10-16

day after surgery. Mechanical pain were detected by Von Frey tests

anxiety and depression behaviors were separately detected by the open field and the tail tailing experiments

while the morphology of CA3 pyramidal neurons were qualified by the Golgi-staining.

Result:

Compared with sham group

significant decreases of the mechanical pain thresholds

decreases of the duration time in the open field

as well as the increases of the no-struggling time during the tail-suspension were detected in the SNL mice(

0.01). In addition

as illustrated by the Golgi-staining

the atrophy of hippocampal pyramidal neurons were found in SNL mice as compared with sham(

0.05

0.01). On the contrary

as compared to the SNL

significant increases of the mechanical pain thresholds

increases of the duration time in the open field

the decreases of the no-struggling time during the tail-suspension(

0.01)

as well as the morphological improvements of the hippocampal CA3 pyramidal neurons were detected in the WTT mice. Furthermore

after 7 d hippocampal injections

There is no significant distinction of the mechanical pain thresholds

the duration time in the open field

the no-struggling time during the tail-suspension

as well as the atrophy of hippocampal neurons were detected in the WTT-ANA12 groups as compared with SNL.

Conclusion:

The data suggested that the effective inhibition of WTT on SNL-induced vertebral neuron injury in hippocampus CA3 and pain-emotion disorder

which might attribute to it' s regulation of BDNF/TrkB pathway in hippocampus.

关键词

Keywords

references

V O Hecke ， S K Austin ， R A Khan ， et al . Neuropathic pain in the general population：a systematic review of epidemiological studies [J]． Pain ， 2014 ， 155 ( 4 )： 654 - 662 .

F Radat ， A Margot-Duclot ， N Attal ． Psychiatric co-morbidities in patients with chronic peripheral neuropathic pain：a multicenter cohort study [J]． Eur J Pain ， 2013 ， 17 ( 10 )： 1547 - 1557 .

田润利，郭朝晖，李永男．神经病理性疼痛对海马影响的研究进展 [J]．疑难病杂志， 2017 ， 16 ( 11 )： 1166 - 1170 .

A Blugeot ， C Rivat ， E Bouvier ， et al . Vulnerability to depression：from brain neuroplasticity to identification of biomarkers [J]． J Neurosci ， 2011 ， 31 ( 36 )： 12889 - 12899 .

张仲景．金匮要略 [M]．北京：中医古籍出版社， 1997 ： 14 .

冯振宇，赵杰，马小娟，等．助阳开郁方对抑郁症大鼠海马BDNF表达及其胞内信号转导通路的影响 [J]．山西中医学院学报， 2018 ， 19 ( 6 )： 21 - 24 .

X Y LI ， N WANG ， Y J WANG ， et al . Long-term temporal imprecision of information coding in the anterior cingulate cortex of mice with peripheral inflammation or nerve injury [J]． J Neurosci ， 2014 ，( 32 )： 10675 - 10687 .

白光辉，张建华．加减乌头汤治疗三叉神经痛28例 [J]．现代中西医结合杂志， 2003 ， 12 ( 4 )： 385 .

C WANG ， X KONG ， C ZHU ， et al . Wutou Tang attenuates neuropathic pain via suppressing spinal astrocytic IL-1R1/TRAF6/JNK signaling [J]． Oncotarget ， 2017 ， 8 ( 54 )： 92864 - 92879 .

C ZHU , Q XU , C WANG , et al . Evidence that CA3 is underling the comorbidity between pain and depression and the Co-curation by Wutou Tang in neuropathic pain [J]． Sci Rep ， 2017 ， 7 ( 1 )： 11935 .

C Q LI ， J M XU ， D LIU ， et al . Brain derived neurotrophic factor(BDNF)contributes to the pain hypersensitivity following surgical incision in the rats [J]． Mol Pain ， 2008 ， 4 ( 27 )： 1 - 11 .

S Kim ， J Chung ． An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat [J]． Pain ， 1992 ， 50 ( 3 )： 355 - 363 .

S R Chaplan ， F W Bach ， J W Pogrel ， et al . Quantitative assessment of tactile allodynia in the rat paw [J]． J Neurosci Methods ， 1994 ， 53 ( 1 )： 55 - 63 .

刘兵，尹维宏．实验基础医学 [M]．西安：第四军医大学出版社， 2007 ： 316 .

A Can ， R A Blackwell ， S C Piantadosi ． Antidepressant-like responses to lithium in genetically diverse mouse strains [J]. Genes Brain Behav ， 2011 ， 10 ( 4 )： 434 - 443 .

S H Kim , J M Chung . An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat [J]． Pain ， 1992 ， 50 ( 3 )： 355 - 363 .

I Yalcin ， F Barthas ， M Barrot ． Emotional consequences of neuropathic pain：insight from preclinical studies [J]． Neurosci Biobehav Rev ， 2014 ， 47 ： 154 - 164 .

黄宇光，徐建国．神经病理疼痛临床诊疗学 [M]．北京：人民卫生出版社， 2010 ： 3611 - 3678 .

N B Finnerup ， N Attal ， S Haroutounian ， et al . Pharmacotherapy for neuropathic pain in adults：a systematic review and meta-analysis [J]． Lancet Neurol ， 2015 ， 14 ( 2 )： 162 - 173 .

C ZHU ， Q XU , N LIN ． The Chinese medicine Wutou Tang relieves neuropathic pain by inhibiting hippocampal microglia activation [J]． Sci Rep ， 2018 ， 8 ( 16 )： 12292 .

毛志云，许琼虹，朱春燕，等．乌头汤改善下行抑制系统损伤以缓解神经病理性疼痛的作用机制 [J]．中国实验方剂学杂志， 2018 ， 24 ( 5 )： 82 - 87 .

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Related Author

Hong-yan WU

Yu-qi SHI

Jia-hao LI

Chun-yan ZHU

Na LIN

Yu-qi SHI

Hong-yan WU

Na LIN

Related Institution

Institute of Chinese Materia Medica，China Academy of Chinese Medical Sciences

Guangzhou University of Chinese Medicine

Heilongjiang University of Chinese Medicine

Graduate School of Heilongjiang University of Chinese Medicine

Tengzhou TCM Hospital，Tengzhou

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