鞘内注射胶质细胞源性神经营养因子对大鼠糖尿病神经病理性疼痛的影响

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Abstract Objective To explore the effect of glial cell line-derived neurotrophic factor (GDNF) on the behavior of rats with diabetic neuropathic pain (DNP). Methods Fifty male SD rats were randomly divided into the control group (N group,n=10) and model group(n=40). After modeling, the model group was randomly divided into the DNP group (DC group,n=10,given 10 μl PBS buffer alone) and GDNF treatment group (DG group, n=10,injected with 2 μg GDNF + 10 μl PBS buffer). The rats in each group had their mechanical threshold of tail pressing (TFT) and paw withdrawal latency (PWL) measured before modeling, on the 3rd and 21st days after modeling, and on the 1st, 3rd, 7th, and 14th days after the first injection of GDNF or PBS buffer. After the rats were sacrificed, L_4-6 spinal cord tissues were collected, and the expression levels of phosphorylated PI3K, p-AKT, p-mTOR and p-S6K were determined by Western blot. Results On the 21st day after modeling, the blood glucose of the model group was significantly increased compared with the N group, (P<0.01), while the TFT and PWL were significantly reduced (P<0.01). On the 14th day after administration, the TFT and PWL of the DG group were significantly increased compared with the DC group (P<0.01), but the expressions of phosphorylated PI3K, p-AKT, p-mTOR and p-S6K were significantly decreased (P<0.01). On the 14th day after administration, the TFT and PWL of the DC group were significantly decreased compared with the N group (P<0.01), but the expressions of phosphorylated PI3K, p-AKT, p-mTOR and p-S6K were significantly increased (P<0.01). On the 14th day after the drug, the expressions of TFT, PWL and phosphorylated PI3K, p-AKT, p-mTOR and p-S6K in the DG group were not significantly different from those of the N group. Conclusions Intrathecal injection of GDNF can relieve DNP in rats. The mechanism may be related to GDNF’s inhibition of expressions of p-mTOR and p-S6K by regulating the PI3K-AKT signaling pathway and reducing the expression level of p-AKT.

Key words： glial cell line-derived neurotrophic factor diabetic neuropathic pain p-mTOR p-S6K

Received: 10 October 2021

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	Articles by authors
	CHEN Yizhou
	WANG Ying
	ZHAO Dan
	SUN Li
	LIU Yongzhe
	GUO Wenzhi
	GAO Minglong

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CHEN Yizhou,WANG Ying,ZHAO Dan等. Effects of intrathecal injection of glial cell-derived neurotrophic factor on diabetic neuropathic pain in rats[J]. Med. J. Chin. Peop. Armed Poli. Forc., 2022, 33(3): 238-242.

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http://journal08.magtechjournal.com/Jwk_wjyx/EN/ OR http://journal08.magtechjournal.com/Jwk_wjyx/EN/Y2022/V33/I3/238

[1]	中国医师协会神经内科医师分会疼痛和感觉障碍专委会. 糖尿病性周围神经病理性疼痛诊疗专家共识[J]. 全科医学临床与教育, 2019, 17(2):100-107.
[2]	Lin L, Doherty D, Lile J, et al. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons[J]. Science, 1993, 260(5111):1130-1132.
[3]	Love S, Plaha P, Patel N K, et al. Glial cell line-derived neurotrophic factor induces neuronal sprouting in human brain[J]. Nat Med, 2005, 11(7):703-704.
[4]	Patel N K, Gill S S. GDNF delivery for Parkinson's disease[J]. Acta Neurochir(Wien), 2007, 97(2 Suppl):135-154.
[5]	Boucher T J, Okuse K, Bennett D L, et al. Potent analgesic effects of GDNF in neuropathic pain states[J]. Science, 2000, 290(5489):124-127.
[6]	袁佳, 刘功俭. 鞘内注射GDNF对神经病理性疼痛大鼠的影响及可能机制[J]. 徐州医学院学报, 2013, 33(6):398-401.
[7]	Parekh P A, Garcia T X, Hofmann M C. Regulation of GDNF expression in Sertoli cells[J]. Reproduction, 2019, 157(3):95-107.
[8]	金学廷, 邱正红, 刘向国. 胶质细胞源性神经营养因子在大鼠神经病理性疼痛模型中的作用及机制研究[J]. 中国现代医学杂志, 2021, 31(11):37-42.
[9]	贾东林, 吴新民, 张利萍. 蛛网膜下腔注射胶质细胞源性神经营养因子对大鼠神经病理性痛的影响[J]. 中国疼痛医学杂志, 2009, 15(4):221-225.
[10]	郭建荣, 贾东林, 喻君, 等. 鞘内注射GDNF对神经病理性疼痛大鼠脊髓NO含量和NOS活性的影响[J]. 中国疼痛医学杂志, 2011, 17(3):171-175.
[11]	Henderson C E, Phillips H S, Pollack R A, et al. GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle[J]. Science, 1994, 266(5187):1062-1064.
[12]	Bowenkamp K E, Lapchak P A, Hoffer B J, et al. Glial cell line-derived neurotrophic factor reverses motor impairment in 16-17 month old rats[J]. Neurosci Lett, 1996, 211(2):81-4.
[13]	郭建荣. 胶质细胞源性神经营养因子与神经病理性疼痛[J]. 中国药理学通报, 2009, 25(10):1278-1281.
[14]	Tian Y X, Shen L F, Li F J, et al. Silencing of RHEB inhibits cell proliferation and promotes apoptosis in colorectal cancer cells via inhibition of the mTOR signaling pathway[J]. J Cell Physiol, 2020, 235(1):442-453.
[15]	Costa-Mattioli M, Sossin W S, Klann E, et al. Translational control of long-lasting synaptic plasticity and memory[J]. Neuron, 2009, 61(1):10-26.
[16]	Hoeffer C A,Klann E. mTOR signaling: at the crossroads of plasticity, memory and disease[J]. Trends Neurosci, 2010, 33(2):67-75.
[17]	Tillu D V, Melemedjian O K, Asiedu M N, et al. Resveratrol engages AMPK to attenuate ERK and mTOR signaling in sensory neurons and inhibits incision-induced acute and chronic pain [J]. Mol Pain, 2012, 8(1):5.
[18]	Melemedjian O K, Asiedu M N, Tillu D V, et al. Targeting adenosine monophosphate-activated protein kinase(AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain[J]. Mol Pain, 2011, 7(1):70.
[19]	Zhang X L, Jiang N, Li J, et al. Rapamycin alleviates proinflammatory cytokines and nociceptive behavior induced by chemotherapeutic paclitaxel[J]. Neurol Res, 2019, 41(1):52-59.
[20]	Berliocchi L, Russo R, Levato A, et al. (-)-Linalool attenuates allodynia in neuropathic pain induced by spinal nerve ligation in c57/bl6 mice.[J]. Int Rev Neurol, 2009, 85(1):221-235.
[21]	Shi J Y, Liu G S, Liu L F, et al. Glial cell line-derived neurotrophic factor gene transfer exerts protective effect on axons in sciatic nerve following constriction-induced peripheral nerve injury[J]. Hum Gene Ther, 2011, 22(6):721-731.
[22]	Sun R Q, Tu Y J, Yan J Y, et al. Activation of protein kinase B/Akt signaling pathway contributes to mechanical hypersensitivity induced by capsaicin[J]. Pain, 2006, 120(1-2):86-96.
[23]	王存金, 庞君, 李莉, 等. 鞘内注射GDNF对神经病理性疼痛大鼠脊髓水平p-Akt表达的影响[J]. 中国疼痛医学杂志, 2014, 20(4):208-212.
[24]	何万友, 王汉兵, 杨承祥, 等. 鞘内注射雷帕霉素对大鼠糖尿病神经痛的影响[J]. 中华麻醉学杂志, 2014, 34(1):4.
[25]	Drel V R, Lupachyk S, Shevalye H, et al. New therapeutic and biomarker discovery for peripheral diabetic neuropathy: PARP inhibitor, nitrotyrosine, and tumor necrosis factor-α[J]. Endocrinology, 2010, 151(6):2547-2555.
[26]	Purwata T. High TNF-alpha plasma levels and macrophages iNOS and TNF-alpha expression as risk factors for painful diabetic neuropathy[J]. J Pain Res, 2011,4(1):169-175.
[27]	Bierhaus A, Fleming T, Stoyanov S, et al. Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy[J]. Nat Med, 2012, 18(6):926-33.
[28]	Lee D F, Kuo H P, Chen C T, et al. IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway[J]. Cell, 2007, 130(3):440-455.
[29]	Dan H C, Cooper M J, Cogswell P C, et al. Akt-dependent regulation of NF-κB is controlled by mTOR and Raptor in association with IKK[J]. Genes Dev, 2008, 22(11):1490.
[30]	Cheng H T, Dauch J R, Sang S O, et al. p38 mediates mechanical allodynia in a mouse model of type 2 diabetes[J]. Mol Pain, 2010, 6(1):28.