Full Text:   <1823>

Summary:  <1555>

CLC number: R587.2

On-line Access: 2020-03-02

Received: 2019-07-19

Revision Accepted: 2019-11-12

Crosschecked: 2020-02-04

Cited: 0

Clicked: 2803

Citations:  Bibtex RefMan EndNote GB/T7714


Lan Xu


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2020 Vol.21 No.2 P.166-171


CX3CR1 contributes to streptozotocin-induced mechanical allodynia in the mouse spinal cord

Author(s):  Cheng-ming Ni, Bing-yu Ling, Xiang Xu, He-ping Sun, Hui Jin, Yu-qiu Zhang, Hong Cao, Lan Xu

Affiliation(s):  Department of Endocrinology, the Affiliated Wuxi Peoples Hospital of Nanjing Medical University, Wuxi 214023, China; more

Corresponding email(s):   hongcao@fudan.edu.cn, xulan126@126.com

Key Words:  FKN/CX3CR1, Mechanical allodynia, STZ-induced diabetic mice

Cheng-ming Ni, Bing-yu Ling, Xiang Xu, He-ping Sun, Hui Jin, Yu-qiu Zhang, Hong Cao, Lan Xu. CX3CR1 contributes to streptozotocin-induced mechanical allodynia in the mouse spinal cord[J]. Journal of Zhejiang University Science B, 2020, 21(2): 166-171.

@article{title="CX3CR1 contributes to streptozotocin-induced mechanical allodynia in the mouse spinal cord",
author="Cheng-ming Ni, Bing-yu Ling, Xiang Xu, He-ping Sun, Hui Jin, Yu-qiu Zhang, Hong Cao, Lan Xu",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T CX3CR1 contributes to streptozotocin-induced mechanical allodynia in the mouse spinal cord
%A Cheng-ming Ni
%A Bing-yu Ling
%A Xiang Xu
%A He-ping Sun
%A Hui Jin
%A Yu-qiu Zhang
%A Hong Cao
%A Lan Xu
%J Journal of Zhejiang University SCIENCE B
%V 21
%N 2
%P 166-171
%@ 1673-1581
%D 2020
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900439

T1 - CX3CR1 contributes to streptozotocin-induced mechanical allodynia in the mouse spinal cord
A1 - Cheng-ming Ni
A1 - Bing-yu Ling
A1 - Xiang Xu
A1 - He-ping Sun
A1 - Hui Jin
A1 - Yu-qiu Zhang
A1 - Hong Cao
A1 - Lan Xu
J0 - Journal of Zhejiang University Science B
VL - 21
IS - 2
SP - 166
EP - 171
%@ 1673-1581
Y1 - 2020
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1900439

Patients with diabetic peripheral neuropathy experience debilitating pain that significantly affects their quality of life (Abbott et al., 2011), by causing sleeping disorders, anxiety, and depression (Dermanovic Dobrota et al., 2014). The primary clinical manifestation of painful diabetic neuropathy (PDN) is mechanical hypersensitivity, also known as mechanical allodynia (MA) (Callaghan et al., 2012). MA’s underlying mechanism remains poorly understood, and so far, based on symptomatic treatment, it has no effective therapy (Moore et al., 2014).


方法:本实验采用健康雄性C57BL/6小鼠与CX3CR1 KO小鼠,体重20~23 g,隔夜禁食12 h(20点至次日8点),并连续三天腹腔注射100 mg/kg的STZ制备T1DM模型.以空腹血糖浓度>11.1 mmol/L且三周后小鼠机械痛阈值明显下降的情况视为T1DM模型制备成功.在小鼠机械痛阈下降的对应时间点,取腰段脊髓背角,采用蛋白质印迹法(western blot)和免疫组化法测定CX3CL1及CX3CR1的表达情况.同时,在发生机械痛阈值下降的第三周时间鞘内给予CX3CR1的中和抗体,进行机械刺激并观察其痛阈值的变化.
结论:STZ诱导的T1DM动物模型在早期表现为显著的机械诱发痛,并伴随脊髓背角CX3CL1/CX3CR1表达上调;在痛阈下降期鞘内给予CX3CR1的中和抗体可抑制糖尿病小鼠的痛行为.与腹腔注射STZ形成T1DM的C57BL/6小鼠相比,CX3CR1 基因敲除的糖尿病小鼠机械痛阈值下降的时间延迟,程度减轻.因此,我们推测CX3CL1/ CX3CR1可能参与T1DM机械痛的形成与发展.


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Abbott CA, Malik RA, van Ross ERE, et al., 2011. Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K. Diabetes Care, 34(10):2220-2224.

[2]Badr G, Badr BM, Mahmoud MH, et al., 2012. Treatment of diabetic mice with undenatured whey protein accelerates the wound healing process by enhancing the expression of MIP-1α, MIP-2, KC, CX3CL1 and TGF-β in wounded tissue. BMC Immunol, 13:32.

[3]Callaghan BC, Cheng HT, Stables CL, et al., 2012. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol, 11(6):521-534.

[4]Cameron NE, Eaton SEM, Cotter MA, et al., 2001. Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia, 44(11):1973-1988.

[5]Cao H, Zhao YQ, 2008. Spinal glial activation contributes to pathological pain states. Neurosci Biobehav Rev, 32(5):972-983.

[6]Clark AK, Yip PK, Malcangio M, 2009. The liberation of fractalkine in the dorsal horn requires microglial cathepsin S. J Neurosci, 29(21):6945-6954.

[7]Dansereau MA, Gosselin RD, Pohl M, et al., 2008. Spinal CCL2 pronociceptive action is no longer effective in CCR2 receptor antagonist-treated rats. J Neurochem, 106(2):757-769.

[8]Dermanovic Dobrota V, Hrabac P, Skegro D, et al., 2014. The impact of neuropathic pain and other comorbidities on the quality of life in patients with diabetes. Health Qual Life Outcomes, 12:171.

[9]Guo XX, Wang Y, Wang K, et al., 2018. Stability of a type 2 diabetes rat model induced by high-fat diet feeding with low-dose streptozotocin injection. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(7):559-569.

[10]Inoguchi T, Li P, Umeda F, et al., 2000. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes, 49(11):1939-1945.

[11]Ji RR, Chamessian A, Zhang YQ, 2016. Pain regulation by non-neuronal cells and inflammation. Science, 354(6312):572-577.

[12]Kiyomoto M, Shinoda M, Okada-Ogawa A, et al., 2013. Fractalkine signaling in microglia contributes to ectopic orofacial pain following trapezius muscle inflammation. J Neurosci, 33(18):7667-7680.

[13]Lee YS, Morinaga H, Kim JJ, et al., 2013. The fractalkine/CX3CR1 system regulates β cell function and insulin secretion. Cell, 153(2):413-425.

[14]Lindia JA, McGowan E, Jochnowitz N, et al., 2005. Induction of CX3CL1 expression in astrocytes and CX3CR1 in microglia in the spinal cord of a rat model of neuropathic pain. J Pain, 6(7):434-438.

[15]Mika J, Zychowska M, Popiolek-Barczyk K, et al., 2013. Importance of glial activation in neuropathic pain. Eur J Pharmacol, 716(1-3):106-119.

[16]Milligan E, Zapata V, Schoeniger D, et al., 2005. An initial investigation of spinal mechanisms underlying pain enhancement induced by fractalkine, a neuronally released chemokine. Eur J Neurosci, 22(11):2775-2782.

[17]Moore RA, Wiffen PJ, Derry S, et al., 2014. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev, (4):CD007938.

[18]Nishikawa T, Edelstein D, Du XL, et al., 2000. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature, 404(6779):787-790.

[19]Oyama T, Miyasita Y, Watanabe H, et al., 2006. The role of polyol pathway in high glucose-induced endothelial cell damages. Diabetes Res Clin Pract, 73(3):227-234.

[20]Rajchgot T, Thomas SC, Wang JC, et al., 2019. Neurons and microglia; a sickly-sweet duo in diabetic pain neuropathy. Front Neurosci, 13:25.

[21]Souza GR, Talbot J, Lotufo CM, et al., 2013. Fractalkine mediates inflammatory pain through activation of satellite glial cells. Proc Natl Acad Sci USA, 110(27):11193-11198.

[22]Sugimoto K, Yasujima M, Yagihashi S, 2008. Role of advanced glycation end products in diabetic neuropathy. Curr Pharm Des, 14(10):953-961.

[23]Svensson CI, Fitzsimmons B, Azizi S, et al., 2005. Spinal p38β isoform mediates tissue injury-induced hyperalgesia and spinal sensitization. J Neurochem, 92(6):1508-1520.

[24]Tsuda M, Inoue K, Salter MW, 2005. Neuropathic pain and spinal microglia: a big problem from molecules in ‘small’ glia. Trends Neurosci, 28(2):101-107.

[25]Xu AK, Gong Z, He YZ, et al., 2019. Comprehensive therapeutics targeting the corticospinal tract following spinal cord injury. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(3):205-218.

[26]Yao L, Wu YT, Tian GX, et al., 2017. Acrolein scavenger hydralazine prevents streptozotocin-induced painful diabetic neuropathy and spinal neuroinflammation in rats. Anat Rec (Hoboken), 300(10):1858-1864.

[27]Zhang Y, Yan J, Hu R, et al., 2015. Microglia are involved in pruritus induced by DNFB via the CX3CR1/p38 MAPK pathway. Cell Physiol Biochem, 35(3):1023-1033.

[28]Zhao H, Alam A, Chen Q, et al., 2017. The role of microglia in the pathobiology of neuropathic pain development: what do we know? Br J Anaesth, 118(4):504-516.

[29]Zochodne DW, Verge VMK, Cheng C, et al., 2000. Nitric oxide synthase activity and expression in experimental diabetic neuropathy. J Neuropathol Exp Neurol, 59(9):798-807.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE