Abstract | BACKGROUND: METHODS: The rat chronic post-ischemic pain ( CPIP) model that mimics human CRPS-I was established. RNA-sequencing ( RNA-Seq), qPCR, Western blot, immunostaining, and pharmacological studies were used for profiling gene changes in ipsilateral spinal cord dorsal horn (SCDH) of CPIP model rat and further validation. RESULTS:
CPIP rats developed persistent mechanical allodynia in bilateral hind paws, accompanied with obvious glial activation in SCDH. RNA-Seq identified a total of 435 differentially expressed genes (DEGs) in ipsilateral SCDH of CPIP rats. qPCR confirmed the expression of several representative genes. Functional analysis of DEGs identified that the most significantly enriched biological processes of upregulated genes include inflammatory and innate immune response. We further identified NLRP3 inflammasome expression to be significantly upregulated in SCDH of CPIP rats. Pharmacological blocking NLRP3 inflammasome reduced IL-1β overproduction, glial activation in SCDH as well as mechanical allodynia of CPIP rats. CONCLUSION: Our study revealed that immune and inflammatory responses are predominant biological events in SCDH of CPIP rats. We further identified NLRP3 inflammasome in SCDH as a key contributor to the pain and inflammation responses in CPIP rats. Thus, our study provided putative novel targets that may help to develop effective therapeutics against CRPS-I.
|
Authors | Ruixiang Chen, Chengyu Yin, Qimiao Hu, Boyu Liu, Yan Tai, Xiaoli Zheng, Yuanyuan Li, Jianqiao Fang, Boyi Liu |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 17
Issue 1
Pg. 162
(May 23 2020)
ISSN: 1742-2094 [Electronic] England |
PMID | 32446302
(Publication Type: Journal Article)
|
Chemical References |
- Inflammasomes
- NLR Family, Pyrin Domain-Containing 3 Protein
- Nlrp3 protein, rat
|
Topics |
- Animals
- Disease Models, Animal
- Gene Expression Profiling
- Inflammasomes
(genetics, immunology, metabolism)
- Inflammation
(genetics, immunology, metabolism)
- Male
- NLR Family, Pyrin Domain-Containing 3 Protein
(genetics, immunology, metabolism)
- Pain
(genetics, immunology, metabolism)
- Rats
- Rats, Sprague-Dawley
- Reflex Sympathetic Dystrophy
(genetics, immunology, metabolism)
- Spinal Cord Dorsal Horn
(immunology, metabolism)
|