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European Spine Journal

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Open Access 01-11-2014 | Original Article

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

Authors: Hiroharu Saito, Jun Wakai, Miho Sekiguchi, Shinichi Kikuchi, Shinichi Konno

Published in: European Spine Journal | Issue 11/2014

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.

Aoki Y, Rydevik B, Kikuchi S et al (2002) Local applications of disc-related cytokines on spinal nerve roots. Spine 27:1614–1617PubMedCrossRef

Boje KM, Arora PK (1992) Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death. Brain Res 587:250–256PubMedCrossRef

Brisby H, Byröd G, Olmarker K et al (2000) Nitric oxide as a mediator of nucleus pulposus-induced effects on spinal nerve roots. J Orthop Res 18:815–820PubMedCrossRef

Calingasan NY, Park LC, Calo LL et al (1998) Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism. Am J Pathol 153:599–610PubMedCrossRefPubMedCentral

Chizh BA, Illes P (2001) P2X receptors and nociception. Pharmacol Rev 53:553–568PubMed

Driessen B, Reimann W, Selve N et al (1994) Antinociceptive effect of intrathecally administered P2-purinoceptor antagonists in rats. Brain Res 666:182–188PubMedCrossRef

Georg WK (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19:312–318CrossRef

Giulian D, Baker TJ, Shih LC et al (1986) Interleukin 1 of the central nervous system is produced by ameboid microglia. J Exp Med 164:594–604PubMedCrossRef

Hamanoue M, Takemoto N, Matsumoto K et al (1996) Neurotrophic effect of hepatocyte growth factor on central nervous system neurons in vitro. J Neurosci Res 43:554–564PubMedCrossRef

10.

Hanisch UK (2002) Micoglia as a source and target of cytokines. Glia 40:140–155PubMedCrossRef

11.

Olmarker K, Larsson K (1998) Tumor necrosis factor alpha and nucleus pulposus induced nerve root injury. Spine 23:2538–2544PubMedCrossRef

12.

Hugel S, Schlichter R (2000) Presynaptic P2X receptors facilitate inhibitory GABAergic transmission between cultured rat spinal cord dorsal horn neurons. J Neurosci 20:2121–2130PubMed

13.

Igarashi T, Kikuchi S, Shuvayev V et al (2000) Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology: molecular, histologic, and behavioral comparisons in rat. Spine 25:2975–2980PubMedCrossRef

14.

Kato K, Kikuchi S, Konno S et al (2008) Participation of 5-hydroxytryptamine in pain-related behavior induced by nucleus pulposus applied on the nerve root in rats. Spine 33(12):1330–1336PubMedCrossRef

15.

Kayama S, Konno S, Olmarker K et al (1996) Incision of the annulus fibrosus induces nerve root morphologic, vascular, and functional changes: an experimental study. Spine 21:2539–2543PubMedCrossRef

16.

Kawakami M, Tamaki T, Weinstein JN et al (1996) Pathomechanism of pain-related behavior produced by allografts of intervertebral disc in the rat. Spine 21:2101–2107PubMedCrossRef

17.

Kawakami M, Tamaki T, Hashizume H et al (1997) The role of phospholipase A2 and nitric oxide in pain-related behavior produced by an allograft of intervertebral disc material to the sciatic nerve of the rat. Spine 22:1074–1079PubMedCrossRef

18.

19.

Keller AF, Beggs S, Salter MW et al (2007) Transformation of the output of spinal lamina I neurons after nerve injury and microglia stimulation underlying neuropathic pain. Mol Pain 3:27PubMedCrossRefPubMedCentral

20.

Kennedy C, Assis TS, Currie AJ et al (2003) Crossing the pain barrier: P2 receptors as targets for novel analgesics. J Physiol 553:683–694PubMedCrossRefPubMedCentral

21.

Khakh BS, Burnstick G, Kennedy C et al (2001) International union of pharmacology. Current status of the nomenclature and properties of P2X receptors and their subunits. Pharmacol Rev 53:107–118PubMed

22.

Kobayashi H, Kikuchi S, Konno S et al (2011) Interaction of 5-hydroxytryptamine and tumor necrosis factor-alpha to pain-related behavior by nucleus pulposus applied on the nerve root in rats. Spine 36(3):210–218PubMedCrossRef

23.

Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19:312–318PubMedCrossRef

24.

Li P, Calejesan AA, Zhuo M (1998) ATP P2X receptors and sensory synaptic transmission between primary afferent fibers and spinal dorsal horn neurons in rats. J Neurophysiol 80:3356–3360PubMed

25.

Merrill JE (1991) Effects of interleukin-1 and tumor necrosis factor-alpha on astrocytes, microglia, oligodendrocytes, and glial precursors in vitro. Dev Neurosci 13:130–137PubMedCrossRef

26.

Miyoshi S, Sekiguchi M, Konno S et al (2011) Increased expression of vascular endothelial growth factor protein in dorsal root ganglion exposed to nucleus pulposus on the nerve root in rats. Spine 36(1):E1–E6PubMedCrossRef

27.

Nagata K, Imai T, Yamashita T et al (2009) Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief. Mol Pain 5:20PubMedCrossRefPubMedCentral

28.

Nakatsuka T, Tsuzuki K, Ling JX et al (2003) Distinct roles of P2X receptors in modulating glutamate release at different primary sensory synapses in rat spinal cord. J Neurophysiol 89:3243–3252PubMedCrossRef

29.

Olmarker K, Rydevik B, Nordborg C (1993) Autologous nucleus pulposus induces neurophysiologic and histologic changes in porcine cauda equine nerve roots. Spine 18:1425–1432PubMedCrossRef

30.

Olmarker K, Brisby H, Yabuki S et al (1997) The effects of normal, frozen, and hyaluronidase-digested nucleus pulposus on nerve root structure and function. Spine 22:471–476PubMedCrossRef

31.

Olmarker K, Myers RR (1998) Pathogenesis of sciatic pain: role of herniated nucleus pulposus and deformation of spinal nerve root and dorsal root ganglion. Pain 78:99–105CrossRef

32.

Olmarker K, Larsson K (1998) Tumor necrosis factor alpha and nucleus pulposus induced nerve root injury. Spine 23:2538–2544PubMedCrossRef

33.

Otoshi K, Kikuchi S, Konno S et al (2010) The reactions of glial cells and endoneurial macrophages in the dorsal root ganglion and their contribution to pain-related behavior after application of nucleus pulposus onto the nerve root in rats. Spine 35(3):264–271PubMedCrossRef

34.

Peng B, Wu W, Li Z et al (2007) Chemical radiculitis. Pain 127:11–16PubMedCrossRef

35.

Ji R-R, Suter MR (2007) P38 MAPK, microglial signaling, and neuropathic pain. Mol Pain 3:33PubMedCrossRefPubMedCentral

36.

Saarto T, Wiffen P (2010) Antidepressants for neuropathic pain: a chochrane review. J Neurol Neurosurg Phychiatry 81:1372–1373CrossRef

37.

Sekiguchi M, Otoshi K, Kikuchi S et al (2011) Analgesic effects of prostaglandin E2 receptor subtype EP1 receptor antagonist: experimental study of application of nucleus pulposus. Spine 36(22):1829–1834PubMedCrossRef

38.

Shubayev VI, Myers RR (2001) Axonal transport of TNF-alpha in painful neuropathy: distribution of ligand tracer and TNF receptors. J Neuroimmunol 114:48–56PubMedCrossRef

39.

Shubayev VI, Myers RR (2002) Anterograde TNF alpha transport from rat dorsal root ganglion to spinal cord and injured sciatic nerve. Neurosci Lett 320:99–101PubMedCrossRef

40.

Smith ME, van der Maesen K, Somera FP (1998) Macrophage and microglial responses to cytokines in vitro: phagocytic activity, proteolytic enzyme release, and free radical production. J Neurosci Res 54:68–78PubMedCrossRef

41.

Streit WJ, Graeber MB, Kreutzberg GW (1998) Functional plasticity of microglia: a review. Glia 1:301–307CrossRef

42.

Streit WJ, Walter SA, Pennell NA (1999) Reactive microgliosis. Prog Neurobiol 57:563–581PubMedCrossRef

43.

Stoll G, Jander S (1999) The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 58:233–247PubMedCrossRef

44.

Tsuda M, Ueno S, Inoue K (1999) In vivo pathway of thermal hyperalgesia by intrathecal administration of α,β-methylene ATP in mouse spinal cord: involvement of the glutamate-NMDA receptor system. Br J Pharmacol 127:449–456PubMedCrossRefPubMedCentral

45.

Tsuda M, Shigemoto-Mogami Y, Koizumi S et al (2003) P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 424:778–783PubMedCrossRef

46.

Wagner R, Myers RR (1996) Schwann cells produce TNF-alpha: expression in injured and non-injured nerves. Neuroscience 73:625–629PubMedCrossRef

47.

Wagner R, Myers RR (1996) Endoneurial injection of TNF alpha produces neuropathic pain behaviors. Neuro Report 7:2897–2901

48.

Wuertz K, Quero L, Sekiguchi M et al (2011) The red wine polyphenol resveratrol shows promising potential for the treatment of nucleus pulposus-mediated pain in vitro and in vivo. Spine 36(21):E1373–E1384PubMedCrossRef

Title: The effect of selective serotonin reuptake inhibitor (SSRI) on pain-related behavior in a rat model of neuropathic pain
Authors: Hiroharu Saito
Jun Wakai
Miho Sekiguchi
Shinichi Kikuchi
Shinichi Konno
Publication date: 01-11-2014
Publisher: Springer Berlin Heidelberg
Published in: European Spine Journal / Issue 11/2014
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-014-3392-x

2024 ASCO Annual Meeting

Springer Medicine

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

Abstract

Introduction

Materials and methods

Results

Conclusion

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Introduction

Materials and methods

Results

Conclusion

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