Enhanced RAGE Expression in the Dorsal Root Ganglion May Contribute to Neuropathic Pain Induced by Spinal Nerve Ligation in Rats

Pain Med. 2016 May;17(5):803-12. doi: 10.1093/pm/pnv035. Epub 2015 Dec 7.


Objective: There is some evidence implicating receptor for advanced glycation end products (RAGE) signaling in the pathogenesis of neuropathic pain (NP). The objective was to investigate whether RAGE signaling in the dorsal root ganglion (DRG) might contribute to NP following peripheral nerve injury.

Design: Experimental study before and after spinal nerve ligation (SNL) surgery.

Setting: Caged in a controlled environment.

Subjects: Male Sprague-Dawley rats.

Methods: A SNL rat model of NP was used. Mechanical hyperalgesia was measured by the paw withdrawal threshold (PWT) to mechanical stimuli (1.4-15 g). Protein expressions of RAGE (immunofluorescence and western blotting), glial fibrillary acidic protein (GFAP; satellite glial cell [SGC] activation marker), IL-1β (ELISA), TNF-α (ELISA), and NF-κB (western blotting) in the DRG were determined. RAGE signaling was inhibited by intrathecal injection of anti-RAGE antibody.

Results: After 7 days, SNL surgery reduced the PWT and upregulated the protein expression of RAGE, GFAP, NF-κB, TNF-α, and IL-1β. Intrathecal injection of RAGE-neutralizing antibody attenuated the SNL-induced mechanical hyperalgesia, activation of SGCs, and upregulation of NF-κB, TNF-α, and IL-1β in the DRG.

Conclusion: RAGE signaling may contribute to the pain hypersensitivity observed in the rat SNL model of NP. Although the precise mechanism remains to be established, NF-κB, TNF-α, and IL-1β likely play a role, together with the activation of SGCs.

Keywords: Advanced Glycation End Products; Dorsal Root Ganglion; Satellite Glial Cell; Spinal Nerve Ligation; Neuropathic Pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / administration & dosage
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Gene Expression Regulation
  • Injections, Spinal
  • Ligation
  • Male
  • Neuralgia / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor for Advanced Glycation End Products / antagonists & inhibitors
  • Receptor for Advanced Glycation End Products / biosynthesis*
  • Spinal Nerves / drug effects
  • Spinal Nerves / injuries*


  • Ager protein, rat
  • Antibodies, Neutralizing
  • Receptor for Advanced Glycation End Products