Papers of the Week

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 the present study, we used a model of chronic compression of dorsal root ganglion (CCD)-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 (p-AXL) and AXL were localized primarily on isolectin B4 (IB4)-positive and calcitonin gene-related peptide (CGRP)-positive neurons, while AXL was also localized in neurofilament-200 (NF200)-positive neurons. CCD-induced pain was associated with the upregulation of AXL mRNA and protein in injured DRGs. Repeated intrathecal administration of the AXL inhibitor, TP0903, or the AXL small interfering RNA (AXL siRNA), effectively alleviated CCD-induced pain hypersensitivities. Moreover, repeated intrathecal administration of either TP0903, or AXL siRNA, reduced the expression of mTOR in injured DRGs, suggesting that mTOR may mediate AXL's actions. These results indicate that the upregulation of DRG AXL may be part of a peripheral mechanism of neuropathic pain via an intracellular mTOR-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.