Microglia activation and temporal changes in rat model of trigeminal neuralgia

doi:10.7518/hxkq.2022.06.003

Abstract

Abstract:

Objective This study aimed to investigate whether the microglia in the spinal trigeminal nucleus caudal part (Sp5C) were activated in a rat model of trigeminal neuralgia and to explore whether the activation level of microglia is consistent with maxillofacial pain level. Methods Chronic constriction injury of trigeminal nerve (CCI) was induced by partial ligation of infraorbital nerve (IoN) in rats. The behavioral change of rats observed at D1, D5, D10, D15, and D30 days post-surgery and the change of pain threshold were detected with electronic Von Frey filaments served as an evaluation index of maxillofacial pain. Weight change was measured by weighing. Ionized calcium binding adaptor molecule-1 (Iba-1) expression level of Sp5C at each time point was detected, and three microglia morphological categories were analyzed by immunohistochemical staining. Results The changes of behavioral and pain threshold suggested the maxillofacial pain level first increased and then decreased post-surgery in the IoN-CCI group. Both the expressions of Iba-1 and proportion of ameboid morphology in ipsilateral Sp5C increased from D1 and reached their peaks in D10 and D5, respectively. Then, they recovered nearly to the same level with contralateral Sp5C on D30. This trend was consistent with the maxillofacial change. Conclusion The model of trigeminal neuralgia in rats constructed by partial ligation of infraorbital nerve can induce the activation of microglia in Sp5C, and the activation level is consistent with maxillofacial pain, which reached its peak at around D10 post-surgery.

Key words: trigeminal neuralgia, microglia, neuropathic pain, animal model

CLC Number:

R 745.1

Lu Yanzhu, Zhang Jingqi, Lai Wenli.. Microglia activation and temporal changes in rat model of trigeminal neuralgia[J]. West China Journal of Stomatology, 2022, 40(6): 638-644.

Figures/Tables 7

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References 22

1	Sanchez-Larsen A, Sopelana D, Diaz-Maroto I, et al. Assessment of efficacy and safety of eslicarbazepine acetate for the treatment of trigeminal neuralgia[J]. Eur J Pain, 2018, 22(6): 1080-1087.
2	Zhao H, Wang XH, Zhang Y, et al. Management of primary bilateral trigeminal neuralgia with microvascular decompression: 13-case series[J]. World Neurosurg, 2018, 109: e724-e730.
3	Tsai YH, Yuan R, Patel D, et al. Altered structure and functional connection in patients with classical trigeminal neuralgia[J]. Hum Brain Mapp, 2018, 39(2): 609-621.
4	Kobayashi M, Nakaya Y. Anatomical aspects of corticotrigeminal projections to the medullary dorsal horn[J]. J Oral Sci, 2020, 62(2): 144-146.
5	Giordano KR, Denman CR, Dubisch PS, et al. An update on the rod microglia variant in experimental and clinical brain injury and disease[J]. Brain Commun, 2021, 3(1): fcaa227.
6	Graeber MB. Changing face of microglia[J]. Science, 2010, 330(6005): 783-788.
7	Young K, Morrison H. Quantifying microglia morpho-logy from photomicrographs of immunohistochemistry prepared tissue using imageJ[J]. J Vis Exp, 2018(136): 57648.
8	Pomilio C, Gorojod RM, Riudavets M, et al. Microglial autophagy is impaired by prolonged exposure to β-amyloid peptides: evidence from experimental models and Alzheimer’s disease patients[J]. Geroscience, 2020, 42(2): 613-632.
9	Bathla G, Hegde AN. The trigeminal nerve: an illustrated review of its imaging anatomy and pathology[J]. Clin Radiol, 2013, 68(2): 203-213.
10	Zuo X, Ling JX, Xu GY, et al. Operant behavioral responses to orofacial cold stimuli in rats with chronic constrictive trigeminal nerve injury: effects of menthol and capsazepine[J]. Mol Pain, 2013, 9: 28.
11	Fink BR, Aasheim G, Kish SJ, et al. Neurokinetics of lidocaine in the infraorbital nerve of the rat in vivo: relation to sensory block[J]. Anesthesiology, 1975, 42(6): 731-736.
12	Henry MA, Fairchild DD, Patil MJ, et al. Effect of a novel, orally active matrix metalloproteinase-2 and -9 inhibitor in spinal and trigeminal rat models of neuropa-thic pain[J]. J Oral Facial Pain Headache, 2015, 29(3): 286-296.
13	Ding WH, You ZR, Shen SQ, et al. An improved rodent model of trigeminal neuropathic pain by unilateral chro-nic constriction injury of distal infraorbital nerve[J]. J Pain, 2017, 18(8): 899-907.
14	Dingle A, Zeng WF, Ness JP, et al. Strategies for interfa-cing with the trigeminal nerves in rodents for bioelectric medicine[J]. J Neurosci Methods, 2019, 324: 108321.
15	Imamura Y, Kawamoto H, Nakanishi O. Characterization of heat-hyperalgesia in an experimental trigeminal neuropathy in rats[J]. Exp Brain Res, 1997, 116(1): 97-103.
16	樊林花, 李丹, 樊平花, 等. 清洁级SD大鼠体重和主要脏器系数正常参考值研究及相关性分析[J]. 中国卫生检验杂志, 2012, 22(4): 750-752.
	Fan LH, Li D, Fan PH, et al. Study and correlation analysis of normal reference range of body weight and the main organs coefficient of clean SD rat[J]. Chin J Heal Lab Tech, 2012, 22(4): 750-752.
17	Xia L, Liu MX, Zhong J, et al. Pain threshold monitoring during chronic constriction injury of the infraorbital nerve in rats[J]. Br J Neurosurg, 2019, 33(4): 409-412.
18	Ananthan S, Benoliel R. Chronic orofacial pain[J]. J Neural Transm (Vienna), 2020, 127(4): 575-588.
19	Yatziv SL, Devor M. Suppression of neuropathic pain by selective silencing of dorsal root ganglion ectopia using nonblocking concentrations of lidocaine[J]. Pain, 2019, 160(9): 2105-2114.
20	Catterall WA, Lenaeus MJ, Gamal El-Din TM. Structure and pharmacology of voltage-gated sodium and calcium channels[J]. Annu Rev Pharmacol Toxicol, 2020, 60: 133-154.
21	Goodwin G, McMahon SB. The physiological function of different voltage-gated sodium channels in pain[J]. Nat Rev Neurosci, 2021, 22(5): 263-274.
22	Inoue K, Tsuda M. Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential[J]. Nat Rev Neurosci, 2018, 19(3): 138-152.

时间	空白对照组	假手术组	IoN-CCI组
术前	220.63±7.33	222.00±6.69	224.13±6.79
术后第1天	224.37±7.65	221.25±7.07	220.12±7.02
术后第5天	255.50±7.04	237.25±7.14*	243.50±9.23*
术后第10天	279.50±7.17	259.25±6.82*	249.75±9.92*^#
术后第15天	328.87±6.91	310.37±10.59*	295.13±10.19*^#
术后第30天	381.62±8.66	385.75±9.28	360.50±10.06*^#

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