Roles of serotonin receptor subtypes for the antinociception of 5-HT in the spinal cord of rats

Jeong, Chul; Choi, Jeong Il; Yoon, Myung Ha

doi:10.1016/j.ejphar.2004.08.048

Cited by 107 publications

(59 citation statements)

References 25 publications

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“…Although, the improvements were likely caused by suppression of microglia, and not by a direct effect on the dorsal root ganglion. Of course, this discussion is very limited in that we only analyzed two serotonin receptors when there are several other subtypes of receptors potentially involved in its pain-modulating effects [6,7,19,20,22]. Our study strengthens the evidence for the involvement of 5-HT in the development of pain in disc herniation, but the exact mechanisms are in great need of further research.…”

Section: Discussionsupporting

confidence: 54%

Experimental Disc Herniation in the Rat Causes Downregulation of Serotonin Receptor 2c in a TNF-dependent Manner

Jonsson

Finskas

Fujioka

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background During recent decades, the knowledge of the pathophysiology of disc herniation and sciatica has drastically improved. What previously was considered a strict biomechanical process is now considered a more complex interaction between leaked nucleus pulposus and the tissue in the spinal canal. An inflammatory reaction, with tumor necrosis factor (TNF) playing an essential role, has been demonstrated. However, the exact mechanisms of the pathophysiology of disc herniation remain unknown. Questions/purposes In this study we use an animal model to investigate (1) if and/or how experimental disc herniation affects gene expression in the early phase (24 hours postsurgery) in the dorsal root ganglion; and (2) if TNF inhibition can reduce any observed changes. Methods A rat model of disc herniation was used. Twenty rats were evenly divided into four groups: naïve, sham, disc herniation, and disc herniation with TNF inhibition. The dorsal root ganglion of the affected nerve root was harvested 24 hours after surgery and analyzed with a TaqMan Low Density Array 1 quantitative polymerase chain reaction assay. Gene expression levels in sham were compared with disc herniation to assess question 1 and disc herniation to disc herniation with TNF inhibition to assess question 2. Results Experimental disc herniation caused a decrease in the expression of the serotonin receptor 2c gene (p = 0.022). TNF inhibition was found to reduce the observed decrease in expression of serotonin receptor 2c (p = 0.037). Conclusions Our results suggest that a decrease in the expression of the serotonin receptor 2c gene may contribute to the pathophysiology of disc herniation. Further research on its involvement is warranted. Clinical Relevance This pilot study gives a brief insight into cellular changes that may contribute to the pathophysiology of disc herniation. This knowledge may

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Section: Discussionsupporting

confidence: 54%

Experimental Disc Herniation in the Rat Causes Downregulation of Serotonin Receptor 2c in a TNF-dependent Manner

Jonsson

Finskas

Fujioka

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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“…Bath application of fluvoxamine (10,30, and 100 mM) concentration-dependently inhibited both monosynaptic A-fiber-and C-fiber-mediated EPSCs in SG neurons voltage-clamped at a holding potential of −70 mV. Figure 1B illustrates representative time courses of EPSC suppression in response to fluvoxamine with a gradual recovery upon washout.…”

Section: Effects Of Fluvoxamine On Monosynaptic A-fiber-and C-fiber-mmentioning

confidence: 99%

“…Fluvoxamine inhibited the first EPSC more potently than the second and therefore increased PPR. In 4 neurons tested, fluvoxamine (100 mM) increased the PPR from 0.72 ± 0.06 to 0.93 ± 0.04 (10,30, and 100 mM) and in the presence of WAY100635 (WAY) and tropisetron (Trop), a 5-HT1A receptor antagonist and a 5-HT3 receptor antagonist, respectively, on A-fiber-and C-fibermediated EPSCs. In the presence of WAY100635 or tropisetron, fluvoxamine was applied at 100 mM.…”

Section: Effects Of Fluvoxamine On Paired-pulse Response Of Monosynapmentioning

confidence: 99%

Presynaptic Inhibitory Effects of Fluvoxamine, a Selective Serotonin Reuptake Inhibitor, on Nociceptive Excitatory Synaptic Transmission in Spinal Superficial Dorsal Horn Neurons of Adult Mice

et al. 2014

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Abstract. Fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor, has been shown to exert analgesic effects in humans and laboratory animals. However, its effects on spinal nociceptive synaptic transmission have not been fully characterized. Here, whole-cell recordings were made from dorsal horn neurons in spinal slices with attached dorsal roots from adult mice, and the effects of fluvoxamine on monosynaptic A-fiber-and C-fiber-mediated excitatory postsynaptic currents (EPSCs) evoked in response to electrical stimulation of a dorsal root were studied. Fluvoxamine (10 -100 mM) concentration-dependently suppressed both monosynaptic A-fiberand C-fiber-mediated EPSCs, which were attenuated by the selective 5-HT 1A receptor antagonist WAY100635. In the presence of the selective 5-HT 3 receptor antagonist tropisetron, fluvoxamine hardly suppressed A-fiber-mediated EPSCs, whereas its inhibitory effect on C-fiber-mediated EPSCs was not affected. Although fluvoxamine increased the paired-pulse ratio of A-fibermediated EPSCs, it increased the frequency of spontaneous and miniature EPSCs (sEPSCs and mEPSCs). Since sEPSCs and mEPSCs appeared to arise largely from spinal interneurons, we then recorded strontium-evoked asynchronous events occurring after A-fiber stimulation, whose frequency was reduced by fluvoxamine. These results suggest that fluvoxamine reduces excitatory synaptic transmission from primary afferent fibers via presynaptic mechanisms involving 5-HT 1A and/or 5-HT 3 receptors, which may contribute to its analgesic effects.

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“…5-Hydroxy-3-(2-aminoethyl)indole hydrochloride (5-HT) (Sigma-Aldrich, Saint Louis, MO) was used as a nonselective 5-HT receptor agonist. All other drugs were purchased from Tocris Cook- The doses of the antagonists and agonists were chosen according to our preliminary data and to previous reports (Obata et al, 2001(Obata et al, , 2002Hurley et al, 2003;Jeong et al, 2004). RS 102221, MDL 72222, GR 113808, and CGS 12066 were dissolved in 2.0% dimethyl sulfoxide (DMSO), BZTZ in 8.0% DMSO, and other drugs were dissolved in normal saline (NS).…”

Section: Methodsmentioning

confidence: 99%

Roles of 5-Hydroxytryptamine (5-HT) Receptor Subtypes in the Inhibitory Effects of 5-HT on C-Fiber Responses of Spinal Wide Dynamic Range Neurons in Rats

Liu

Xing²,

Qu³

et al. 2007

J Pharmacol Exp Ther

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5-Hydroxytryptamine (5-HT; serotonin) plays an important role in the descending control of nociception. 5-HT and its receptors have been extensively studied in the modulation of nociceptive transmission at the spinal level using behavioral tests that may be affected by the effects of 5-HT on motor performance and skin temperature. Using electrophysiological methods, the present study aimed to systematically investigate the roles of 5-HT receptor subtypes on the inhibitory effects of 5-HT on responses of the spinal wide dynamic range (WDR) neurons to C-fiber inputs in rats. Under basal conditions, topical application of 5-HT to the spinal cord inhibited the C-fiber responses of WDR neurons dose-dependently, whereas antagonists of 5-HT 1A [WAY 100635 [N-[2-[4-(2- The dorsal horn of the spinal cord is critical for nociceptive transmission. Nociceptive information impinging upon the dorsal horn from the skin, viscera, and other tissues is subjected to segmental, extrasegmental, and descending inhibitory controls (Melzack and Wall, 1965). It has been established that the descending control system from the brain exerts an inhibitory influence upon the spinal processing of nociceptive information. 5-Hydroxytryptamine (5-HT; serotonin) is a major neurotransmitter in the descending control system. In the spinal cord, at least four subtypes of 5-HT receptors (5-HT 1 -5-HT 4 ) have been identified, which are involved in spinal pain modulation. However, the roles of some of these receptor subtypes are not well defined, and previous

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Roles of serotonin receptor subtypes for the antinociception of 5-HT in the spinal cord of rats

Cited by 107 publications

References 25 publications

Experimental Disc Herniation in the Rat Causes Downregulation of Serotonin Receptor 2c in a TNF-dependent Manner

Experimental Disc Herniation in the Rat Causes Downregulation of Serotonin Receptor 2c in a TNF-dependent Manner

Presynaptic Inhibitory Effects of Fluvoxamine, a Selective Serotonin Reuptake Inhibitor, on Nociceptive Excitatory Synaptic Transmission in Spinal Superficial Dorsal Horn Neurons of Adult Mice

Roles of 5-Hydroxytryptamine (5-HT) Receptor Subtypes in the Inhibitory Effects of 5-HT on C-Fiber Responses of Spinal Wide Dynamic Range Neurons in Rats

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