Objective: Chemokine CXCL12 and its receptor CXCR4 have been reported to play a critical role in neurogenesis and neuronal differentiation. Recently, some reports have implicated this chemokine signaling in the pathogenesis of many kinds of pain. However, its role in neuropathic pain (NP) is still largely unclear. This study explored the distribution and function of CXCR4 in spinal cord (SC) dorsal horn (DH) in a rat L5 spinal nerve ligation (SNL) model.
Methods: Rats received repeated intrathecal injection of CXCR4 antagonist AMD3100. Behavioral assessments were conducted using a traditional “up–down” method. The spinal CXCL12 contents were measured by enzyme linked immunosorbent assay. The expression and distribution of CXCR4 in the SC were determined by immunoflurescence and Western blot. GlyRα3 expressions were also measured by Western blot or immunofluorescence.
Results: SNL induced CXCL12–CXCR4 activation in the spinal DH. Intrathecal administration of AMD3100 alleviated the chronic NP against SNL (P <0.01). CXCR4 was colocalized with GlyRα3-positive neurons in the spinal DH at ratio >97%. Meanwhile, AMD3100 rescued the decrease of GlyRα3 expression (P <0.01 vs the SNL group on Day 14 and Day 21).
Conclusion: CXCR4 antagonist can elicit analgesic effects and restore the inhibitory neurotransmission such as GlyRα3 against NP.
Keywords: neuropathic pain, CXCL12, CXCR4, GlyRα3, L5 spinal nerve ligation