title: The effect of serotonin-noradrenaline reuptake inhibitor duloxetine on the intervertebral disk-related radiculopathy in rats.
abstract: BACKGROUND
  Neuropathic pain, commonly related to intervertebral disk (IVD) degeneration, responds poorly to standard pain treatments. Serotonin-noradrenaline reuptake inhibitors (SNRIs) have been reported to reduce neuropathic pain; however their effect on radiculopathy induced by lumbar disk herniation remains unclear. The aim of this study was to investigate the effect of SNRI duloxetine in rat model of IVD-related neuropathic pain.
  
  
  METHODS
  Effects of SNRI duloxetine were tested in Sprague-Dawley rats (n = 135). Neuropathic pain was induced by applying autologous nucleus pulposus (NP) on the left L5 dorsal root ganglion (DRG). Duloxetine in concentrations 0.4 mg/kg (low dose) and 1.2 mg/kg (high dose) or saline were administered orally for 10 days. Von Frey test was carried out on post-operative days 2, 7, 14, 21, and 28 to test pain sensitivity. Immunohistochemistry of L5 DRG and L5 segment of spinal cord (SC) was performed on days 7 and 21 to examine expressions of tumor necrosis factor alpha (TNF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and ionized calcium-binding adapter molecule 1 (Iba1). On days 14, 21, and 28, expressions of TNF in DRG as well as NGF and BDNF in SC were tested by immunoblotting. Sham-operated rats and naive rats were used as controls.
  
  
  RESULTS
  Duloxetine in both concentrations significantly improved pain threshold from postoperative day 21 onward, compared to the NP + saline group (p < 0.05). High-dose duloxetine significantly inhibited the expression of TNF in DRG (day 28, p < 0.05). Both duloxetine concentrations reduced the expression of NGF in SC (day 21, p < 0.05), but the expression of BDNF remained unchanged.
  
  
  CONCLUSIONS
  SNRI duloxetine inhibited neuropathic pain in rats possibly via down-regulating TNF, NGF, and microglia activation. We conclude that duloxetine, and most likely other SNRIs, may be used for the management of lumbar neuropathic pain.
authors.affiliation: Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Handa
authors.affiliation: Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan. miho-s@fmu.ac.jp.
authors.forename: Miho
authors.initials: M
authors.lastname: Sekiguchi
authors.affiliation: Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Olga
authors.initials: O
authors.lastname: Krupkova
authors.affiliation: Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Konno
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D000068736:Duloxetine Hydrochloride / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000150:complications*; D008159:Lumbar Vertebrae / Q000378:metabolism; D023421:Models, Animal; D020932:Nerve Growth Factor / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology; D017288:Pain Threshold; D011843:Radiculopathy / Q000209:etiology*; D017207:Rats, Sprague-Dawley; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D014409:Tumor Necrosis Factor-alpha; D000068736:Duloxetine Hydrochloride; D020932:Nerve Growth Factor
keywords: Antidepressants; Duloxetine; Lumbar disk herniation; Neuropathic pain; Pain-related behavior; Serotonin–noradrenaline reuptake inhibitors (SNRIs)