• The Korean Journal of Pain
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• v.14 no.2
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• pp.136-141
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• 2001

Background: Sodium salicylate (SS) is a nonsteroidal anti-inflammatory drug (NSAID) for the treatment of neuralgia or pain from rheumatoid arthritis. When abused or used in excess, SS can induce cytotoxicity. The present study examined whether SS has a neurotoxic effect. Methods: Cell viability was examined by MTT [3-(4,5-dimethylthiazol-2,5-dipheny ltetrazolium bromide] assay and Sulforhodamine (SRB) assay after cultivating dorsal root ganglion (DRG) neurons derived from neonatal mouse. These cells were treated with various concentrations of SS for 24 hours. In addition, the amount of protein synthesis against SS was measured in these cultures. Results: Cell viability (20, $40{\mu}g/ml$ SS) significantly decreased in a dose-dependent manner. Additionally, SS inhibited protein synthesis after the exposure of cultured mouse DRG neurons to $30{\mu}g/ml$ of SS for 24 hours. Conclusions: The present study suggests that SS is toxic in cultured DRG neurons derived from neonatal mouse by decreasing cell viability and the amount of protein synthesis.

• YAKHAK HOEJI
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• v.56 no.2
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• pp.108-115
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• 2012

The hyperpolarization-activated current ($I_h$) is an inward cation current activated by hyperpolarization of the membrane potential and plays a role as an important modulator of action potential firing frequency in many excitable cells. In the present study we investigated the effects of extracellular divalent cations on $I_h$ in dorsal root ganglion (DRG) neurons using whole-cell voltage clamp technique. $I_h$ was slightly increased in $Ca^{2+}$-free bath solution. BAPTA-AM did not change the amplitudes of $I_h$. Amplitudes of $I_h$ were decreased by $Ca^{2+}$, $Mg^{2+}$ and $Ba^{2+}$ dose-dependently and voltage-independently. Inhibition magnitudes of $I_h$ by external divalent cations were partly reversed by the concomitant increase of extracellular $K^+$ concentration. Reversal potential of $I_h$ was significantly shifted by $Ba^{2+}$ and $V_{1/2}$ was significantly affected by the changes of extracellular $Ca^{2+}$ concentrations. These results suggest that $I_h$ is inhibited by extracellular divalent cations ($Ca^{2+}$, $Mg^{2+}$ and $Ba^{2+}$) by interfering ion influxes in cultured rat DRG neurons.

• Advances in Traditional Medicine
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• v.1 no.1
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• pp.64-70
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• 2000

Effects of Rhizoma gastrodiae on glucose oxidase-induced neurotoxicity was investigated in cultured newborn mouse spinal dorsal root ganglion(DRG) neurons that were treated in the media with or without glucose oxidase. In addition, the protective effect of Rhizoma gastrodiae extract against glucose oxidase-induced neurotoxicity was examined. Cytotoxic values were expressed as a percentage of number of living cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In this paper, exposure of neurons to glucose oxidase resulted in a significant call death in a dose- and time-dependent manners in DRG neuron cultures. The decrease in cell viability induced by the glucose oxidase was blocked by Rhizoma gastrodiae extract. These results indicate that the neuroprotective effect of Rhizoma gastrodiae extract against glucose oxidase-induced neurotoxicity may result from a prevention or attenuation of oxidative damage induced by glucose oxidase.

• The Korean Journal of Pain
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• v.21 no.3
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• pp.202-205
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• 2008

Background: Lumbar radicular pain is a frequent and often debilitating event. Although many treatment methods have been described in several studies, the available evidences regarding efficacy is not sufficient enough to draw definitive conclusions on an optimal therapy regime. Pulsed radiofrequency (RF) treatment was found to exert a beneficial effect on intractable radicular pain in individuals. The purpose of this study was to assess the efficacy of pulsed RF of the dorsal root ganglion for chronic lumbar radicular pain. Methods: Twenty five patients with chronic lumbar radicular pain that was refractory to selective nerve root blockage met the inclusion criteria of our study and received pulsed RF treatment. The average numeric rating scale (NRS) for leg pain during usual activities and the Oswestry disability index (ODI) were measured at 1 and 3 months after the procedure. Results: Of the 25 patients accepted for pulsed RF treatment, one dropped out due to a vertebral compression fracture during this study. ODI and NRS showed a positive trend in favor of the pulsed RF treatment. No significant complications were observed during the study period. Conclusions: It appears that pulsed RF treatment of the lumbar spinal dorsal root ganglion may be an effective treatment method for patients suffering from lumbar radicular pain, and who were not responsive to selective nerve root blockage.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.613-624
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• 1997

Dorsal root ganglion (DRG) is composed of neuronal cell bodies of primary afferents with diverse functions. Various types of ion channels present on DRG neurons may reflect those functions. In the present study, voltage-gated potassium currents in DRG neurons of neonatal rats were characterized by whole-cell voltage clamp method. Two types of delayed rectifier and three types of transient potassium currents were identified according to their electrophysiological properties. The delayed rectifier currents were named $I_{Ke}$ (early inactivating) and $I_{K1}$ (late inactivating). Steady state inactivation of $I_{Ke}$ began from -100 mV lasting until -20 mV. $I_{K1}$ could be distinguished from $I_{Ke}$ by its inactivation voltage range, from -70 mV to +10 mV. Three transient currents were named $I_{Af}$ (fast inactivation), $I_{Ai}$ (intermediate inactivation kinetics), and $I_{As}$ (slow inactivation). $I_{Af}$ showed fast inactivation with time constant of $10.6{\pm}2.0$ msec, $I_{Ai}$ of $36.9{\pm}13.9$ msec, and $I_{As}$ of $60.6{\pm}2.9$ msec at +30 mV, respectively. They also had distinct steady state inactivation range of each. Each cell expressed diverse combination of potassium currents. The cells most frequently observed were those which expressed both $I_{K1}$ and $I_{Af}$, and they had large diameters. The cells expressing $I_{Ke}$ and expressing $I_{Ke}$, $I_{Ai}$, and $I_{As}$ usually had small diameters. Judging from cell diameter, capsaicin sensitivity or action potential duration, candidates for nociceptor were the cells expressing $I_{Ke}$, expressing $I_{Ke}$ and $I_{Ai}$, and expressing $I_{Ke}$ and $I_{As}$. The types and distribution of potassium currents in neonatal rat DRG were similar to those of adult rat DRG (Gold et al, 1996b).

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.252-259
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• 2016

Neuropathic pain is a complex state showing increased pain response with dysfunctional inhibitory neurotransmission. The TREK family, one of the two pore domain $K^+$ (K2P) channel subgroups were focused among various mechanisms of neuropathic pain. These channels influence neuronal excitability and are thought to be related in mechano/thermosensation. However, only a little is known about the expression and role of TREK-1 and TREK-2, in neuropathic pain. It is performed to know whether TREK-1 and/or 2 are positively related in dorsal root ganglion (DRG) of a mouse neuropathic pain model, the chronic constriction injury (CCI) model. Following this purpose, Reverse Transcription Polymerase Chain Reaction (RT-PCR) and western blot analyses were performed using mouse DRG of CCI model and compared to the sham surgery group. Immunofluorescence staining of isolectin-B4 (IB4) and TREK were performed. Electrophysiological recordings of single channel currents were analyzed to obtain the information about the channel. Interactions with known TREK activators were tested to confirm the expression. While both TREK-1 and TREK-2 mRNA were significantly overexpressed in DRG of CCI mice, only TREK-1 showed significant increase (~9 fold) in western blot analysis. The TREK-1-like channel recorded in DRG neurons of the CCI mouse showed similar current-voltage relationship and conductance to TREK-1. It was easily activated by low pH solution (pH 6.3), negative pressure, and riluzole. Immunofluorescence images showed the expression of TREK-1 was stronger compared to TREK-2 on IB4 positive neurons. These results suggest that modulation of the TREK-1 channel may have beneficial analgesic effects in neuropathic pain patients.

• The Korean Journal of Pain
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• v.21 no.1
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• pp.11-17
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• 2008

Background: Peripheral nerve injury induces up-regulation of the calcium channel alpha2delta (${\alpha}2{\delta}$) subunit and TRPM8 in the dorsal root ganglion (DRG) which might contribute to allodynia development. We investigated the expression of the ${\alpha}2{\delta}$ subunit and TRPM8 in the DRG of sympathetically maintained pain (SMP) and sympathetic independent pain (SIP) rat model. Methods: For the SMP model, the L5 and L6 spinal nerves were ligated tightly distal to the DRG. For the SIP model, the tibial and sural nerves were transected, while the common peroneal nerve was spared. After a 7 day postoperative period, tactile and cold allodynia were assessed using von Frey filaments and acetone drops, respectively. Expression of the ${\alpha}2{\delta}$ subunit and TRPM8 in the L5 and L6 DRG were subsequently examined by a Western blot. Results: There were no significant differences between the two models for the thresholds of tactile and cold allodynia. Expression of the ${\alpha}2{\delta}$ subunit in the ipsilateral DRG to the injury was increased as determined on a Western blot as compared to that in the contralateral or sham-operated DRG of the SMP model, but there was no difference in expression seen with the use of the SIP model. There was no difference in the expression of TRPM8 in the ipsilateral DRG to the injury and the contralateral or sham-operated DRG of either model. Conclusions: Up-regulation of the ${\alpha}2{\delta}$ subunit in injured DRG may play a role that contributes to tactile allodynia development in SMP, but not TRPM8 to cold allodynia after peripheral nerve injury.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.173-182
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• 2018

Recent studies have provided several lines of evidence that peripheral administration of oxytocin induces analgesia in human and rodents. However, the exact underlying mechanism of analgesia still remains elusive. In the present study, we aimed to identify which receptor could mediate the analgesic effect of intraperitoneal injection of oxytocin and its cellular mechanisms in thermal pain behavior. We found that oxytocin-induced analgesia could be reversed by $d(CH_2)_5[Tyr(Me)^2,Dab^5]$ AVP, a vasopressin-1a (V1a) receptor antagonist, but not by $desGly-NH_2-d(CH_2)_5[D-Tyr^2,Thr^4]OVT$, an oxytocin receptor antagonist. Single cell RT-PCR analysis revealed that V1a receptor, compared to oxytocin, vasopressin-1b and vasopressin-2 receptors, was more profoundly expressed in dorsal root ganglion (DRG) neurons and the expression of V1a receptor was predominant in transient receptor potential vanilloid 1 (TRPV1)-expressing DRG neurons. Fura-2 based calcium imaging experiments showed that capsaicin-induced calcium transient was significantly inhibited by oxytocin and that such inhibition was reversed by V1a receptor antagonist. Additionally, whole cell patch clamp recording demonstrated that oxytocin significantly increased potassium conductance via V1a receptor in DRG neurons. Taken together, our findings suggest that analgesic effects produced by peripheral administration of oxytocin were attributable to the activation of V1a receptor, resulting in reduction of TRPV1 activity and enhancement of potassium conductance in DRG neurons.

• The Korean Journal of Pain
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• v.24 no.4
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• pp.185-190
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• 2011

Background: Spinal nerve ligation (SNL) injury in rats produces a pain syndrome that includes mechanical and thermal allodynia. Previous studies have indicated that proinflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) play an important role in peripheral mediation of neuropathic pain, and that altered dorsal root ganglion (DRG) function and degree of DRG neuronal apoptosis are associated with spinal nerve injury. The present study was conducted to evaluate the expression of TNF-${\alpha}$ and the extent of apoptosis in the dorsal root ganglion after SNL in rats. Methods: Sprague-Dawley rats were subjected to SNL of the left L5 and L6 spinal nerves distal to the DRG and proximal to the formation of the sciatic nerve. At postoperative day 8, TNF-${\alpha}$ protein levels in the L5.6 DRG were compared between SNL and naive groups using ELISA. In addition, we compared the percentage of neurons injured in the DRG using immunostaining for apoptosis and localization of activated caspase-3. Results: SNL injury produced significant mechanical and cold allodynia throughout the 7-day experimental period. TNF-${\alpha}$ protein levels were increased in the DRG in rats that had undergone SNL ($12.7{\pm}3.2$ pg/100 ${\mu}g$, P < 0.001) when compared with naive rats ($4.1{\pm}1.4$ pg/100 ${\mu}g$). The percentage of neurons or satellite cells co-localized with activated caspase-3 were also significantly higher in rats with SNL than in naive rats (P < 0.001, P < 0.05, respectively). Conclusions: SNL injury produces mechanical and cold allodynia, as well as TNF-${\alpha}$ elevation and apoptosis in the DRG.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.1
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• pp.71-78
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• 2001

Capsaicin, a pungent ingredient of hot pepper, elicits an intense burning pain when applied cutaneously and intradermally. Activation of capsaicin-gated channel in C-type dorsal root ganglion (DRG) neurons produces nonselective cationic currents. Although electrophysiological and biochemical properties of capsaicin-activated current $(I_{CAP})$ were studied, the regulatory mechanism and intracellular signaling pathway are still unclear. In the present study, we investigated the modulations of $I_{CAP}$ by DAMGO $({\mu}-opioid\;agonist)$ and cholecystokinin octapeptide (CCK-8). In 18 out of 86 cells, the amplitude of $I_{CAP}$ was significantly increased by DAMGO and completely reversed after washout, while $I_{CAP}$ was decreased by DAMGO in 25 cells. In 43 cells, DAMGO had no effect on $I_{CAP}$. Mean action potential duration was significantly different between 'increased-by-DAMGO' group and 'decreased-by-DAMGO' group. Mean amplitudes of $I_H$ were not significantly different between both groups. CCK-8 reversibly enhanced the amplitude of $I_{CAP}$ (5/13). DAMGO also increased $I_{CAP}$ amplitude significantly in the same cells. The amplitude of $I_{CAP}$ was increased in additive manner by combined applications of DAMGO and CCK-8 in these cells. These results suggest that DAMGO and CCK-8 can either increase or decrease $I_{CAP}$ presumably depending on the subtypes of DRG cells and classified by electrophysiological properties.