scholarly journals Macrophage Activation in the Dorsal Root Ganglion in Rats Developing Autotomy after Peripheral Nerve Injury

2021 ◽  
Vol 22 (23) ◽  
pp. 12801
Author(s):  
Xiang Xu ◽  
Xijie Zhou ◽  
Jian Du ◽  
Xiao Liu ◽  
Liming Qing ◽  
...  

Autotomy, self-mutilation of a denervated limb, is common in animals after peripheral nerve injury (PNI) and is a reliable proxy for neuropathic pain in humans. Understanding the occurrence and treatment of autotomy remains challenging. The objective of this study was to investigate the occurrence of autotomy in nude and Wistar rats and evaluate the differences in macrophage activation and fiber sensitization contributing to the understanding of autotomy behavior. Autotomy in nude and Wistar rats was observed and evaluated 6 and 12 weeks after sciatic nerve repair surgery. The numbers of macrophages and the types of neurons in the dorsal root ganglion (DRG) between the two groups were compared by immunofluorescence studies. Immunostaining of T cells in the DRG was also assessed. Nude rats engaged in autotomy with less frequency than Wistar rats. Autotomy symptoms were also relatively less severe in nude rats. Immunofluorescence studies revealed increased macrophage accumulation and activation in the DRG of Wistar rats. The percentage of NF200+ neurons was higher at 6 and 12 weeks in Wistar rats compared to nude rats, but the percentage of CGRP+ neurons did not differ between two groups. Additionally, macrophages were concentrated around NF200-labeled A fibers. At 6 and 12 weeks following PNI, CD4+ T cells were not found in the DRG of the two groups. The accumulation and activation of macrophages in the DRG may account for the increased frequency and severity of autotomy in Wistar rats. Our results also suggest that A fiber neurons in the DRG play an important role in autotomy.

2016 ◽  
Vol 12 ◽  
pp. 174480691662904 ◽  
Author(s):  
Shaogen Wu ◽  
Brianna Marie Lutz ◽  
Xuerong Miao ◽  
Lingli Liang ◽  
Kai Mo ◽  
...  

1998 ◽  
Vol 796 (1-2) ◽  
pp. 99-106 ◽  
Author(s):  
Seo Eun Lee ◽  
Hong Shen ◽  
Giulio Taglialatela ◽  
Jin Mo Chung ◽  
Kyungsoon Chung

2020 ◽  
Author(s):  
Cunjin Wang ◽  
Yuchen Pan ◽  
Wenwen Zhang ◽  
Ying Chen ◽  
Chuhan Li ◽  
...  

Background The transcriptional repressor positive regulatory domain I–binding factor 1 (PRDM1) is expressed in adult mouse dorsal root ganglion and regulates the formation and function of peripheral sensory neurons. The authors hypothesized that PRDM1 in the dorsal root ganglion may contribute to peripheral nerve injury–induced nociception regulation and that its mechanism may involve Kv4.3 channel transcriptional repression. Methods Nociception was induced in C57BL/6 mice by applying chronic constriction injury, complete Freund’s adjuvant, or capsaicin plantar injection. Nociceptive response was evaluated by mechanical allodynia, thermal hyperalgesia, cold hyperalgesia, or gait analysis. The role of PRDM1 was evaluated by injection of Prdm1 knockdown and overexpression adeno-associated viruses. The interaction of PRDM1 at the Kv4.3 (Kcnd3) promoter was evaluated by chromatin immunoprecipitation assay. Excitability of dorsal root ganglion neurons was evaluated by whole cell patch clamp recordings, and calcium signaling in spinal dorsal horn neurons was evaluated by in vivo two-photon imaging. Results Peripheral nerve injury increased PRDM1 expression in the dorsal root ganglion, which reduced the activity of the Kv4.3 promoter and repressed Kv4.3 channel expression (injured vs. uninjured; all P < 0.001). Knockdown of PRDM1 rescued Kv4.3 expression, reduced the high excitability of injured dorsal root ganglion neurons, and alleviated peripheral nerve injury–induced nociception (short hairpin RNA vs. Scram; all P < 0.05). In contrast, PRDM1 overexpression in naive mouse dorsal root ganglion neurons diminished Kv4.3 channel expression and induced hyperalgesia (PRDM1 overexpression vs. control, mean ± SD; n = 13; all P < 0.0001) as evaluated by mechanical allodynia (0.6 ± 0.3 vs. 1.2 ± 0.2 g), thermal hyperalgesia (5.2 ± 1.3 vs. 9.8 ± 1.7 s), and cold hyperalgesia (3.4 ± 0.5 vs. 5.3 ± 0.6 s). Finally, PRDM1 downregulation in naive mice reduced the calcium signaling response of spinal dorsal horn neurons to thermal stimulation. Conclusions PRDM1 contributes to peripheral nerve injury–induced nociception by repressing Kv4.3 channel expression in injured dorsal root ganglion neurons. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New


2011 ◽  
Vol 89 (5) ◽  
pp. 689-699 ◽  
Author(s):  
Chung-Ren Lin ◽  
Chien-Hui Yang ◽  
Chiu-En Huang ◽  
Chih-Hsien Wu ◽  
Yi-Shen Chen ◽  
...  

2004 ◽  
Vol 19 (6) ◽  
pp. 1437-1445 ◽  
Author(s):  
Sharon Averill ◽  
Gregory J. Michael ◽  
Peter J. Shortland ◽  
Rachel C. Leavesley ◽  
Von R. King ◽  
...  

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