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- Title
AXL signaling in primary sensory neurons contributes to chronic compression of dorsal root ganglion-induced neuropathic pain in rats.
- Authors
Liang, Lingli; Zhang, Jun; Tian, Lixia; Wang, Shuo; Xu, Linping; Wang, Yingxuan; Guo-Shuai, Qingying; Dong, Yue; Chen, Yu; Jia, Hong; Yang, Xuewei; Yuan, Chunmei
- Abstract
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.
- Subjects
SENSORY neurons; DORSAL root ganglia; SMALL interfering RNA; LUMBAR pain; PROTEIN-tyrosine kinases; NEUROPATHY; LABORATORY rats
- Publication
Molecular Pain, 2020, Vol 16, pN.PAG
- ISSN
1744-8069
- Publication type
Article
- DOI
10.1177/1744806919900814