Relationship between complete Freund’s adjuvant-induced chronic pain-induced negative emotions and morphological changes of hippocampal microglia

LI Wei; LIU Zhi-Wen; ZENG Jia-Yu; ZENG Xue-Qing; YUAN Jing; CAO Wen-Yu; ZHONG Xiao-Lin; WAN Wei

doi:10.16098/j.issn.0529-1356.2021.03.004

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Acta Anatomica Sinica ›› 2021, Vol. 52 ›› Issue (3) : 352-357. DOI: 10.16098/j.issn.0529-1356.2021.03.004

Relationship between complete Freund’s adjuvant-induced chronic pain-induced negative emotions and morphological changes of hippocampal microglia

LI Wei¹ LIU Zhi-wen² ZENG Jia-yu¹ ZENG Xu-qing¹ YUAN Jing¹ ZHONG Xiao-lin^3* WAN Wei^1,4*

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Abstract

Objective To investigate the alteration of mood and hippocampal microglia morphology in a mouse model of chronic inflammatory pain induced by complete Freund’s adjuvant (CFA). Methods Thirty-two male ICR mice were randomly divided into two groups, including normal saline control group (NS) and CFA model group (CFA). The pain model was established by right hindpaw intraplantar CFA injection. The change of mechanical pain threshold after CFA injection was measured by von Frey fiber needle, the locomotor activity and anxiety-like behavior were determined by open field test (OFT), the depression-like behavior was determined by sucrose preference test (SPT) and forced swimming test (FST). The expression of microglia marker ionized calcium binding adaptor molecule-1 (IBA-1) in the hippocampus was determined by immunohistochemistry and its morphological change was analyzed by Sholl analysis. Results Compared with the NS group, the mechanical pain threshold of CFA group decreased significantly (P<0.01). The behavior result showed that the CFA group showed remarkably reduced time in the inner area (P<0.01) compared with the NS group in the open field test；In the sucrose preference test, the percentage of sucrose preference (P<0.01) of CFA mice decreased significantly compared with the NS mice, while the immobility time of CFA mice (P<0.01) increased significantly in the forced swimming test compared with the NS mice. The immunohistochemistry showed that the number of microglia in the dentate gyrus (DG) of CFA mice increased significantly compared with the NS mice. The Sholl analysis result showed that compared with the NS mice, the number of intersections of microglia in hippocampal DG decreased significantly in CFA mice. Conclusion Our finding indicates that the negative emotions in CFA-induced chronic inflammatory pain may be related to the morphological changes of hippocampal microglia in the mice.

Key words

Complete Freund’s adjuvant / Hippocampus / Microglia / Chronic inflammatory pain / Negative emotion / Immunohistochemistry / Mouse

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LI Wei LIU Zhi-wen ZENG Jia-yu ZENG Xu-qing YUAN Jing ZHONG Xiao-lin WAN Wei. Relationship between complete Freund’s adjuvant-induced chronic pain-induced negative emotions and morphological changes of hippocampal microglia[J]. Acta Anatomica Sinica. 2021, 52(3): 352-357 https://doi.org/10.16098/j.issn.0529-1356.2021.03.004

References

［1］ Zhu C, Xu Q, Mao Z, et al. The chinese medicine Wu-Tou decoction relieves neuropathic pain by inhibiting hippocampal microglia activation［J］. Sci Rep, 2018,8(1)12292.

［2］ Ji R, Nackley A, Huh Y, et al. Neuroinflammation and central sensitization in chronic and widespread pain［J］. Anesthesiology, 2018,129(2): 343-366.

［3］ Kuner R, Flor H. Structural plasticity and reorganisation in chronic pain［J］. Nat Rev Neurosci, 2017,18(1): 20-30.

［4］ Marshall PWM, Schabrun S, Knox MF. Physical activity and the mediating effect of fear, depression, anxiety, and catastrophizing on pain related disability in people with chronic low back pain［J］. PLoS One, 2017, 12(7): e180788.

［5］ Ai Amin HA, Atweh SF, Jabbur SJ, et al. Effects of ventral hippocampal lesion on thermal and mechanical nociception in neonates and adult rats［J］. Eur J Neurosci, 2004,20(11): 3027-3034.

［6］ Liu Y, Zhou L, Wang J, et al. TNF-α differentially regulates synaptic plasticity in the hippocampus and spinal cord by microglia-dependent mechanisms after peripheral nerve injury［J］. J Neurosci, 2017,37(4): 871-881.

［7］ Salter MW, Stevens B. Microglia emerge as central players in brain disease［J］. Nat Med, 2017,23(9): 1018-1027.

［8］ Zanier ER, Pischiutta F, Riganti L, et al. Bone marrow mesenchymal stromal cells drive protective M2 microglia polarization after brain trauma［J］. Neurotherapeutics, 2014,11(3): 679-695.

［9］ Vogel DY, Vereyken EJ, Glim JE, et al. Macrophages in inflammatory multiple sclerosis lesions have an intermediate activation status［J］. J Neuroinflamm, 2013,10(1): 35.

［10］ Kim CC, Nakamura MC, Hsieh CL. Brain trauma elicits non-canonical macrophage activation states［J］. J Neuroinflamm, 2016,13(1):117.

［11］ Nimmerjahn A. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo［J］. Science, 2005,308(5726): 1314-1318.

［12］ Kozlowski C, Weimer RM. An automated method to quantify microglia morphology and application to monitor activation state longitudinally in vivo［J］. PLoS One, 2012,7(2): e31814.

［13］ Behr MAAM. Freund’s adjuvant, NOD2 and mycobacteria［J］. Curr Opin Microbiol, 2015,23: 126-132.

［14］ Shao CJ, Gao Y, Zhao L, et al. Co-application of lidocaine and QX-572 induces divergent pain behaviours in mice［J］. J Pharm Pharmacol, 2015,67(9): 1272-1278.

［15］ Luo C, Zhong X, Zhou FH, et al. Peripheral brain derived neurotrophic factor precursor regulates pain as an inflammatory mediator［J］. Sci Rep, 2016,6:27171.

［16］ Zeng JY, Wang Zh, Niu L, et al. Effect of Panax notoginseng total saponin on lipopolysaccharide induced depression-like behavior and expression of microglia in mice ［J］.Acta Anatomica Sinica, 2018,49(2): 166-171.(in Chinese)

曾佳玉, 王贞, 牛磊, 等. 三七总皂苷对脂多糖诱导小鼠抑郁样行为及脑内小胶质细胞表达的影响［J］. 解剖学报, 2018,49(2): 166-171.

［17］ Xu Y, Cao W, Zhou M, et al. Inactivation of BRD7 results in impaired cognitive behavior and reduced synaptic plasticity of the medial prefrontal cortex［J］. Behav Brain Res, 2015,286: 1-10.

［18］ Zhong X, Cao W, Zhao H, et al. MicroRNA-32-5p knockout eliminates lipopolysaccharide-induced depressive-like behavior in mice through inhibition of astrocyte overactivity［J］. Brain Behav Immun, 2020,84: 10-22.

［19］ Hunskaar S, Fasmer OB, Hole K. Formalin test in mice, a useful technique for evaluating mild analgesics［J］. J Neurosci Methods, 1985,14(1): 69-76.

［20］ Abbink MR, Kotah JM, Hoeijmakers L, et al. Characterization of astrocytes throughout life in wildtype and APP/PS1 mice after early-life stress exposure［J］. J Neuroinflamm, 2020,17(1):91.

［21］ Chang MC. Conservative treatments frequently used for chronic pain patients in clinical practice: a literature review［J］. Cureus, 2020,8(12): e9934.

［22］ Liao HY, Hsieh CL, Huang CP, et al. Electroacupuncture attenuates CFA-induced inflammatory pain by suppressing Nav1. 8 through S100B, TRPV1, opioid, and adenosine pathways in mice［J］. Sci Rep, 2017,7: 42531.

［23］ Yang Y, Wang Z, Jin S, et al. Opposite monosynaptic scaling of BLP-vCA1 inputs governs hopefulness-and helplessness-modulated spatial learning and memory［J］. Nat Commun, 2016,7:11935.

［24］ Binley KE, Ng WS, Tribble JR, et al. Sholl analysis: a quantitative comparison of semi-automated methods［J］. J Neurosci Methods, 2014,225: 65-70.

［25］ Garcia-Segura LM, Perez-Marquez J. A new mathematica function to evaluate neuronal morphology using the Sholl analysis［J］. J Neurosci Methods, 2014, 226: 103-109.