• The Korean Journal of Pain
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• 제32권4호
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• pp.280-285
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• 2019

Background: Pulsed radiofrequency (PRF) is a treatment modality that alleviates radicular pain by intermittently applying high-frequency currents adjacent to the dorsal root ganglion. There has been no comparative study on analgesic effect according to the position of the needle tip in PRF treatment. The objective of this study is to evaluate the clinical outcomes of PRF according to the needle tip position. Methods: Patients were classified into 2 groups (group IP [group inside of pedicle] and group OP [group outside of pedicle]) based on needle tip position in the anteroposterior view of fluoroscopy. In the anteroposterior view, the needle tip was advanced medially further than the lateral aspect of the corresponding pedicle in group IP; however, in group OP, the needle tip was not advanced. The treatment outcomes and pain scores were evaluated at 4, 8, and 12 weeks after applying PRF. Results: At 4, 8, and 12 weeks, there were no significant differences between the successful response rate and numerical rating scale score ratio. Conclusions: The analgesic efficacy of PRF treatment did not differ with the needle tip position.

• Journal of Korean Neurosurgical Society
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• 제59권2호
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• pp.98-105
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• 2016

Objective : Lumbar disc herniation can induce sciatica by mechanical compression and/or chemical irritation. The aim of this study was to compare the effects of GCSB-5 (Shinbaro$^{(R)}$) and NSAIDs on pain-related behavior and on the expressions of microglia, astrocytes, CGRP, TRPV1, IL-6, and CX3CL1 in a rat model of lumbar disc herniation. Methods : 112 male Sprague-Dawley rats underwent implantation of nucleus pulposus to a dorsal root ganglion (DRG). Rats were divided into five groups as follows; a saline group (the vehicle control group) (n=27), a 10 mg/kg aceclofenac group (the aceclofenac group) (n=22), and 100, 300 or 600 mg/kg GCSB-5 groups (the GCSB-5 100, 300, or 600 groups) (n=21 for each group). Rats were tested for mechanical allodynia at 3 days after surgery and at 1 day, 3 days, 7 days, 14 days, 21 days, 28 days, 35 days, 42 days, 49 days, and 56 days after treatment commencement. Immunohistochemical staining of microglia (Iba1), astrocytes (GFAP), CGRP, and TRPV1, and PCR for IL-6 and CX3CL1 were performed on spinal dorsal horns and DRGs at 56 days after medication commencement. Results : After 56 days of GCSB-5 300 administration, mechanical withdrawal thresholds were significantly increased (p<0.05), and immunohistochemical expressions of Iba1, GFAP, CGRP, and TRPV1 were reduced than other groups, but this difference was not statistically significant. Conclusion : These results indicate GCSB-5 reduces mechanical allodynia and downregulates neuroglial activity and the expressions of CGRP and TRPV1 in the spinal segments of a rat model of lumbar disc herniation.

• The Korean Journal of Physiology and Pharmacology
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• 제14권1호
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• pp.45-49
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• 2010

R-type $Ca_v2.3$ high voltage-activated $Ca^{2+}$ channels in peripheral sensory neurons contribute to pain transmission. Recently we have demonstrated that, among the six $Ca_v2.3$ isoforms ($Ca_v2.3a{\sim}Ca_v2.3e$), the $Ca_v2.3e$ isoform is primarily expressed in trigeminal ganglion (TG) nociceptive neurons. In the present study, we further investigated expression patterns of $Ca_v2.3$ isoforms in the dorsal root ganglion (DRG) neurons. As in TG neurons, whole tissue RT-PCR analyses revealed the presence of two isoforms, $Ca_v2.3a$ and $Ca_v2.3e$, in DRG neurons. Single-cell RT-PCR detected the expression of $Ca_v2.3e$ mRNA in 20% (n=14/70) of DRG neurons, relative to $Ca_v2.3a$ expression in 2.8% (n=2/70) of DRG neurons. $Ca_v2.3e$ mRNA was mainly detected in small-sized neurons (n=12/14), but in only a few medium-sized neurons (n=2/14) and not in large-sized neurons, indicating the prominence of $Ca_v2.3e$ in nociceptive DRG neurons. Moreover, $Ca_v2.3e$ was preferentially expressed in tyrosine-kinase A (trkA)-positive, isolectin B4 (IB4)-negative and transient receptor potential vanilloid 1 (TRPV1)-positive neurons. These results suggest that $Ca_v2.3e$ may be the main R-type $Ca^{2+}$ channel isoform in nociceptive DRG neurons and thereby a potential target for pain treatment, not only in the trigeminal system but also in the spinal system.

• The Korean Journal of Pain
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• 제21권3호
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• pp.187-196
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• 2008

Background: Upregulation of one type of the pro-inflammatory chemokine (CCL2) and its receptor (CCR2) following peripheral nerve injury contributes to the induction of neuropathic pain. Here, we examined whether another type of chemokine (CCL3) is involved in neuropathic pain. Methods: We measured changes in mechanical and thermal sensitivity in the hind paws of naïve rats or rats with an L5 spinal nerve ligation (SNL) after intra-plantar injection of CCL3 or met-RANTES, an antagonist of the CCL3 receptor, CCR1. We also measured CCL3 levels in the sciatic nerve and the hind paw skin as well as CCR1 expression in dorsal root ganglion (DRG) cells from the lumbar spinal segments. Results: Intra-plantar injection of CCL3 into the hind paw of naive rats mimicked L5 SNL-produced hyperalgesia. Intra-plantar injection of met-RANTES into the hind paw of rats with L5 SNL attenuated hyperalgesia. L5 SNL increased CCL3 levels in the sciatic nerve and the hind paw skin on the affected side. The number of CCR1-positive DRG cells in the lumbar segments was not changed following L5 SNL. Conclusions: Partial peripheral nerve injury increases local CCL3 levels along the degenerating axons during Wallerian degeneration. This CCL3 binds to its receptor, CCR1, located on adjacent uninjured afferents, presumably nociceptors, to induce hyperalgesia in the neuropathic pain state.

• The Korean Journal of Pain
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• 제22권1호
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• pp.1-15
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• 2009

Neuropathic pain is often refractory to intervention because of the complex etiology and an incomplete understanding of the mechanisms behind this type of pain. Glial cells, specifically microglia and astrocytes, are powerful modulators of pain and new targets of drug development for neuropathic pain. Glial activation could be the driving force behind chronic pain, maintaining the noxious signal transmission even after the original injury has healed. Glia express chemokine, purinergic, toll-like, glutaminergic and other receptors that enable them to respond to neural signals, and they can modulate neuronal synaptic function and neuronal excitability. Nerve injury upregulates multiple receptors in spinal microglia and astrocytes. Microglia influence neuronal communication by producing inflammatory products at the synapse, as do astrocytes because they completely encapsulate synapses and are in close contact with neuronal somas through gap junctions. Glia are the main source of inflammatory mediators in the central nervous system. New therapeutic strategies for neuropathic pain are emerging such as targeting the glial cells, novel pharmacologic approaches and gene therapy. Drugs targeting microglia and astrocytes, cytokine production, and neural structures including dorsal root ganglion are now under study, as is gene therapy. Isoform-specific inhibition will minimize the side effects produced by blocking all glia with a general inhibitor. Enhancing the anti-inflammatory cytokines could prove more beneficial than administering proinflammatory cytokine antagonists that block glial activation systemically. Research on therapeutic gene transfer to the central nervous system is underway, although obstacles prevent immediate clinical application.

• 동의생리병리학회지
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• 제22권4호
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• pp.896-902
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• 2008

Yukmijihwang-tang(YM) is used in Oriental medicine for treatments of diverse systemic symptoms including neurological dosorders. The present study was performed to examine potential effects of YM on growth-promoting activity of injured sciatic nerve axons. YM treatment in the injured sciatic nerve induced enhanced distal elongation of injured axons when measured 3 and 7 days after injury. Retrograde tracing of sciatic nerve axons showed YM-mediated increases in the number of DiI-labeled dorsal root ganglion (DRG) sensory neurons and spinal cord motor neurons at 3 days after injury. Hoechst nuclear staining showed that non-neuronal cell population was largely elevated by YM treatment in distal nerve area undergoing axonal regeneration. Furthermore, phospho-Erk1/2 protein levels were upregulated by YM treatment in the injured nerve area. These data suggest that YM may play a role in facilitated axonal regeneration in injured peripheral nerves. Further investigations of individual herbal components would be useful to explore effective molecular components and develop therapeutic strategies.

• 동의생리병리학회지
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• 제17권2호
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• pp.503-509
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• 2003

The purpose of this study is to examine the toxic effects caused by xanthine oxidase/hypoxanthine (XO/HX) and the effects of herbal extracts such as Mangeum-tang (萬金湯: MGT) and Gamimangeum-tang (加味萬金湯: GMGT) on the treatment of the toxic effects. The results of these experiments were XO/HX, an oxygen radical-generating system, decreased the survival rates of the cultured cells on XTT assay, the amount of DNA syntheses, and the amount of neurofilaments, and increased c-fos positive cells, MGT and GMGT have the efficacy of increasing the survival rates of the cultured cells by increasing the amount of neurofilaments and DNA synthesis and decreasing the c-fos positive cells damaged by XO/HX, From the above results, it is suggested that MGT and GMGT have marked efficacy as a treatment for the damages caused by the XO/HX-mediated oxidative stress. And MGT and GMGT are thought to have certain pharmacological effects.

• The Korean Journal of Pain
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• 제25권2호
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• pp.94-98
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• 2012

Background: An intravenous infusion of lidocaine has been used on numerous occasions to produce analgesia in neuropathic pain. In the cases of failed back surgery syndrom, the pain generated as result of abnormal impulse from the dorsal root ganglion and spinal cord, for instance as a result of nerve injury may be particularly sensitive to lidocaine. The aim of the present study was to identify the effects of IV lidocaine on neuropathic pain items of FBSS. Methods: The study was a randomized, prospective, double-blinded, crossover study involving eighteen patients with failed back surgery syndrome. The treatments were: 0.9% normal saline, lidocaine 1 mg/kg in 500 ml normal saline, and lidocaine 5 mg/kg in 500 ml normal saline over 60 minutes. The patients underwent infusions on three different appointments, at least two weeks apart. Thus all patients received all 3 treatments. Pain measurement was taken by visual analogue scale (VAS), and neuropathic pain questionnaire. Results: Both lidocaine (1 mg/kg, 5 mg/kg) and placebo significantly reduced the intense, sharp, hot, dull, cold, sensitivity, itchy, unpleasant, deep and superficial of pain. The amount of change was not significantly different among either of the lidocaine and placebo, or among the lidocaine treatments themselves, for any of the pain responses, except sharp, dull, cold, unpleasant, and deep pain. And VAS was decreased during infusion in all 3 group and there were no difference among groups. Conclusions: This study shows that 1 mg/kg, or 5 mg/kg of IV lidocaine, and palcebo was effective in patients with neuropathic pain attributable to FBSS, but effect of licoaine did not differ from placebo saline.

• Journal of Veterinary Science
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• 제22권1호
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• pp.9.1-9.11
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• 2021

Background: Scalding burn injuries can occur in everyday life but occur more frequently in young children. Therefore, it is important to develop more effective burn treatments. Objectives: This study examined the effects of bee venom (BV) stimulation on scalding burn injury-induced nociception in mice as a new treatment for burn pain. Methods: To develop a burn injury model, the right hind paw was immersed temporarily in hot water (65℃, 3 seconds). Immediately after the burn, BV (0.01, 0.02, or 0.1 mg/kg) was injected subcutaneously into the ipsilateral knee area once daily for 14 days. A von Frey test was performed to assess the nociceptive response, and the altered walking parameters were evaluated using an automated gait analysis system. In addition, the peripheral and central expression changes in substance P (Sub P) were measured in the dorsal root ganglion and spinal cord by immunofluorescence. Results: Repeated BV treatment at the 2 higher doses used in this study (0.02 and 0.1 mg/kg) alleviated the pain responses remarkably and recovered the gait performances to the level of acetaminophen (200 mg/kg, intraperitoneal, once daily), which used as the positive control group. Moreover, BV stimulation had an inhibitory effect on the increased expression of Sub P in the peripheral and central nervous systems by a burn injury. Conclusions: These results suggest that a peripheral BV treatment may have positive potency in treating burn-induced pain.

• The Korean Journal of Pain
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• 제34권1호
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• pp.4-18
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• 2021

Except for carbamazepine for trigeminal neuralgia, gabapentinoid anticonvulsants have been the standard for the treatment of neuropathic pain. Pregabalin, which followed gabapentin, was developed with the benefit of rapid peak blood concentration and better bioavailability. Mirogabalin besylate (DS-5565, Tarlige®) shows greater sustained analgesia due to a high affinity to, and slow dissociation from, the α2δ-1 subunits in the dorsal root ganglion (DRG). Additionally, it produces a lower level of central nervous system-specific adverse drug reactions (ADRs), due to a low affinity to, and rapid dissociation from, the α2δ-2 subunits in the cerebellum. Maximum plasma concentration is achieved in less than 1 hour, compared to 1 hour for pregabalin and 3 hours for gabapentin. The plasma protein binding is relatively low, at less than 25%. As with all gabapentinoids, it is also largely excreted via the kidneys in an unchanged form, and so the administration dose should also be adjusted according to renal function. The equianalgesic daily dose for 30 mg of mirogabalin is 600 mg of pregabalin and over 1,200 mg of gabapentin. The initial adult dose starts at 5 mg, given orally twice a day, and is gradually increased by 5 mg at an interval of at least a week, to 15 mg. In conclusion, mirogabalin is anticipated to be a novel, safe gabapentinoid anticonvulsant with a greater therapeutic effect for neuropathic pain in the DRG and lower ADRs in the cerebellum.