AXL signaling in primary sensory neurons contributes to chronic compression of dorsal root ganglion-induced neuropathic pain in rats

Autor: Chunmei Yuan, Lixia Tian, Lingli Liang, Shuo Wang, Xuewei Yang, Qingying Guo-Shuai, Jun Zhang, Hong Jia, Linping Xu, Yingxuan Wang, Yu Chen, Yue Dong
Rok vydání: 2020
Předmět:
Male
dorsal root ganglion
Subfamily
Sensory Receptor Cells
Sensory system
Constriction
Pathologic
Receptor tyrosine kinase
Rats
Sprague-Dawley
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Dorsal root ganglion
030202 anesthesiology
Ganglia
Spinal
medicine
Animals
RNA
Small Interfering
Cells
Cultured
Injections
Spinal
mammalian target of rapamycin
neuropathic pain
Behavior
Animal
biology
business.industry
Nerve Compression Syndromes
AXL
Receptor Protein-Tyrosine Kinases
social sciences
Low back pain
Rats
Disease Models
Animal
Anesthesiology and Pain Medicine
medicine.anatomical_structure
Microscopy
Fluorescence
Gene Knockdown Techniques
chronic compression of dorsal root ganglion
Neuropathic pain
biology.protein
Neuralgia
Molecular Medicine
medicine.symptom
business
Neuroscience
030217 neurology & neurosurgery
Research Article
Zdroj: Molecular Pain
ISSN: 1744-8069
DOI: 10.1177/1744806919900814
Popis: Low back pain is a chronic, highly prevalent, and hard-to-treat condition in the elderly. Clinical studies indicate that AXL, which belongs to the tyrosine kinase receptor subfamily, mediates pathological pain. However, it is not clear exactly how AXL regulates pain behaviors. In this study, we used a model of chronic compression of dorsal root ganglion-induced neuropathic pain to recreate clinical intervertebral foramen stenosis and related lumbocrural pain to explore whether AXL in primary sensory neurons contributes to this neuropathic pain in rats. Using double-labeling immunofluorescence, we observed that both phosphorylated AXL and AXL were localized primarily on isolectin B4-positive and calcitonin gene-related peptide-positive neurons, while AXL was also localized in neurofilament-200-positive neurons. Chronic compression of dorsal root ganglion-induced pain was associated with the upregulation of AXL mRNA and protein in injured dorsal root ganglia. Repeated intrathecal administration of the AXL inhibitor, TP0903, or the AXL small interfering RNA effectively alleviated chronic compression of dorsal root ganglion-induced pain hypersensitivities. Moreover, repeated intrathecal administration of either TP0903 or AXL small interfering RNA reduced the expression of mammalian target of rapamycin in injured dorsal root ganglia, suggesting that mammalian target of rapamycin may mediate AXL’s actions. These results indicate that the upregulation of dorsal root ganglion AXL may be part of a peripheral mechanism of neuropathic pain via an intracellular mammalian target of rapamycin-signaling pathway. Thus, while AXL inhibitors have so far primarily shown clinical efficacy in tumor treatment, AXL intervention could also serve as a potential target for the treatment of neuropathic pain.
Databáze: OpenAIRE
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