PMID- 26394856
OWN - NLM
STAT- MEDLINE
DCOM- 20161020
LR  - 20220321
IS  - 1432-0932 (Electronic)
IS  - 0940-6719 (Linking)
VI  - 25
IP  - 3
DP  - 2016 Mar
TI  - The effect of serotonin-noradrenaline reuptake inhibitor duloxetine on the 
      intervertebral disk-related radiculopathy in rats.
PG  - 877-87
LID - 10.1007/s00586-015-4239-9 [doi]
AB  - INTRODUCTION: 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. MATERIALS AND 
      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. CONCLUSION: 
      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.
FAU - Handa, Junichi
AU  - Handa J
AD  - Department of Orthopaedic Surgery, Fukushima Medical University School of 
      Medicine, Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
FAU - Sekiguchi, Miho
AU  - Sekiguchi M
AD  - Department of Orthopaedic Surgery, Fukushima Medical University School of 
      Medicine, Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan. miho-s@fmu.ac.jp.
FAU - Krupkova, Olga
AU  - Krupkova O
AD  - Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
FAU - Konno, Shin-Ichi
AU  - Konno S
AD  - Department of Orthopaedic Surgery, Fukushima Medical University School of 
      Medicine, Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
LA  - eng
PT  - Journal Article
DEP - 20150922
PL  - Germany
TA  - Eur Spine J
JT  - European spine journal : official publication of the European Spine Society, the 
      European Spinal Deformity Society, and the European Section of the Cervical Spine 
      Research Society
JID - 9301980
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Serotonin and Noradrenaline Reuptake Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9044SC542W (Duloxetine Hydrochloride)
RN  - 9061-61-4 (Nerve Growth Factor)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Duloxetine Hydrochloride/*pharmacology
MH  - Ganglia, Spinal/metabolism
MH  - Intervertebral Disc Degeneration/*complications
MH  - Lumbar Vertebrae/metabolism
MH  - Models, Animal
MH  - Nerve Growth Factor/metabolism
MH  - Neuralgia/*drug therapy/etiology
MH  - Pain Threshold
MH  - Radiculopathy/*etiology
MH  - Rats, Sprague-Dawley
MH  - Serotonin and Noradrenaline Reuptake Inhibitors/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Antidepressants
OT  - Duloxetine
OT  - Lumbar disk herniation
OT  - Neuropathic pain
OT  - Pain-related behavior
OT  - Serotonin-noradrenaline reuptake inhibitors (SNRIs)
EDAT- 2015/09/24 06:00
MHDA- 2016/10/21 06:00
CRDT- 2015/09/24 06:00
PHST- 2015/04/21 00:00 [received]
PHST- 2015/09/10 00:00 [accepted]
PHST- 2015/08/17 00:00 [revised]
PHST- 2015/09/24 06:00 [entrez]
PHST- 2015/09/24 06:00 [pubmed]
PHST- 2016/10/21 06:00 [medline]
AID - 10.1007/s00586-015-4239-9 [pii]
AID - 10.1007/s00586-015-4239-9 [doi]
PST - ppublish
SO  - Eur Spine J. 2016 Mar;25(3):877-87. doi: 10.1007/s00586-015-4239-9. Epub 2015 Sep 
      22.