The effect of selective serotonin reuptake inhibitor (SSRI) on pain-related behavior in a rat model of neuropathic pain

Eur Spine J. 2014 Nov;23(11):2401-9. doi: 10.1007/s00586-014-3392-x. Epub 2014 Jun 5.

Abstract

Introduction: Some antidepressants are effective for treating neuropathic pain independent of any effect on depression. Selective serotonin reuptake inhibitors (SSRIs) are one of the potential agents to treat neuropathic pain. The aims of this study were to compare the effects of SSRI and non-steroidal anti-inflammatory drugs (NSAIDs) on pain-related behavior and expression of cytokines in a rat model of neuropathic pain.

Materials and methods: Spinal surgery was performed to apply nucleus pulposus (NP) to the dorsal root ganglion (DRG). NP animals were treated with saline (NP + S), meloxicam (NP + M), or low-dose or high-dose paroxetine (NP + PL and NP + PH), respectively. Behavioral testing was performed to investigate the mechanical withdrawal thresholds. The numbers of TNF-immunoreactive (IR) neurons in the DRG and of Iba1-IR microglia in the spinal cord (SC) were evaluated using immunohistochemistry. Expression of TNF in the DRG was examined using Western blots.

Results: The thresholds on days 14, 21, and 28 were higher in the drug-treated animals than in the NP + S group (p < 0.05). The number of TNF-IR neurons in DRGs from the NP + M group increased on day 2 and decreased on day 7, and TNF expression in DRGs was significantly higher in the NP + S group than in the NP + M group on days 7, 14. The number of Iba1-IR microglia in the SC was significantly higher in the NP + S group than in the NP + M, NP + PL, and NP + PH groups on days 7 and 14.

Conclusion: An antidepressant might be a potential agent to treat lumbar disc herniation as well as NSAIDs.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Behavior, Animal / physiology
  • Calcium-Binding Proteins / metabolism*
  • Disease Models, Animal
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism
  • Immunohistochemistry
  • Meloxicam
  • Microfilament Proteins / metabolism*
  • Microglia / metabolism
  • Neuralgia / drug therapy*
  • Neurons / metabolism
  • Paroxetine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Thiazines / pharmacology
  • Thiazoles / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Aif1 protein, rat
  • Anti-Inflammatory Agents, Non-Steroidal
  • Calcium-Binding Proteins
  • Microfilament Proteins
  • Serotonin Uptake Inhibitors
  • Thiazines
  • Thiazoles
  • Tumor Necrosis Factor-alpha
  • Paroxetine
  • Meloxicam