Junichi Handa, Miho Sekiguchi, Olga Krupkova, Shin-ichi Konno


February 2016, Volume 25, Issue 3, pp 877 - 887 Original Article Read Full Article 10.1007/s00586-015-4239-9

First Online: 22 September 2015

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 

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.


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