• The Korean Journal of Pain
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• v.37 no.3
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• pp.233-246
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• 2024

Background: Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats. Methods: This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG. Results: After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001). Conclusions: The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.1
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• pp.101-117
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• 1999

Amyotrophic lateral sclerosis (ALS) is a degenerative neuromuscular disease of unknown etiology in which the upper and lower motor neurons are progressively destroyed. Recent evidences support the role of autoimmune mechanisms in the pathogenesis of ALS. This study investigated the effects of sera from ALS patients on neuromuscular transmission in phrenic nerve-hemidiaphragm preparations and on calcium currents of single isolated dorsal root ganglion (DRG) cells in mice. Mice were injected with either control sera from healthy adults or ALS sera from 18 patients with ALS of sporadic form, for three days. Miniature end plate potential (MEPP) and nerve-evoked end plate potential (EPP) were measured using intracellular recording technique and the quantal content was determined. Single isolated DRG cells were voltage-clamped with the whole-cell configuration and membrane currents were recorded. Sera from 14 of 18 ALS patients caused a significant increase in MEPP frequency in normal Ringer's solution $(4.62{\pm}0.14\;Hz)$ compared with the control $(2.18{\pm}0.15\;Hz).$ In a high $Mg^{2+}/low\;Ca^{2+}$ solution, sera from 13 of 18 ALS patients caused a significant increase in MEPP frequency, from $2.18{\pm}0.31$ Hz to $6.09{\pm}0.38$ Hz. Sera from 11 of 18 patients produced a significant increase of nerve-evoked EPP amplitude, from $0.92{\pm}0.05$ mV to $1.30{\pm}0.04$ mV, while the other seven ALS sera did not alter EPP amplitude. In the ALS group, EPP quantal content was also elevated by the sera of 14 patients (from $1.49{\pm}0.07$ to $2.35{\pm}0.07).$ MEPP frequency and amplitude in wobbler mouse were $4.03{\pm}0.53$ Hz and $1.37{\pm}0.18$ mV, respectively, which were significantly higher than those of wobbler controls (wobblers without the symptoms of wobbler). Sera from ALS patients significantly reduced HVA calcium currents of DRG cells to 42.7% at -10 mV. Furthermore, the inactivation curve shifted to more negative potentials with its half-inactivation potential changed by 6.98 mV. There were, however, significant changes neither in the reversal potential of $I_{Ca}$ nor in the I-V curve. From these results it was concluded that: 1) The serum factors of sporadic ALS patients increase neuromuscular transmission and can alter motor nerve terminal presynaptic function. This suggests that ALS serum factors may play an important role in the early stage of ALS, and 2) Calcium currents in DRG cells were reduced and rapidly inactivated by ALS sera, suggesting that in these cells, ALS serum factors may exert interaction with the calcium channel.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.6
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• pp.511-519
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• 2001

Nimopidine, one of dihydropyridine derivatives, has been widely used to pharmacologically identify L-type Ca currents. In this study, it was tested if nimodipine is a selective blocker for L-type Ca currents in sensory neurons and heterologous system. In mouse dorsal root ganglion neurons (DRG), low concentrations of nimodipine $(<10\;{\mu}M),$ mainly targeting L-type Ca currents, blocked high-voltage-activated calcium channel currents by ${\sim}38%.$ Interestingly, high concentrations of nimodipine $(>10\;{\mu}M)$ further reduced the 'residual' currents in DRG neurons from ${\alpha}_{1E}$ knock-out mice, after blocking L-, N- and P/Q-type Ca currents with $10\;{\mu}M$ nimodipine, $1\;{\mu}M\;{\omega}-conotoxin$ GVIA and 200 nM ${\omega-agatoxin$ IVA, indicating inhibitory effects of nimodipine on R-type Ca currents. Nimodipine $(>10\;{\mu}M)$ also produced the inhibition of both low-voltage-activated calcium channel currents in DRG neurons and ${\alpha}_{1B}\;and\;{\alpha}_{1E}$ subunit based Ca channel currents in heterologous system. These results suggest that higher nimodipine $(>10\;{\mu}M)$ is not necessarily selective for L-type Ca currents. While care should be taken in using nimodipine for pharmacologically defining L-type Ca currents from native macroscopic Ca currents, nimodipine $(>10\;{\mu}M)$ could be a useful pharmacological tool for characterizing R-type Ca currents when combined with toxins blocking other types of Ca channels.

• International Journal of Oral Biology
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• v.38 no.1
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• pp.13-19
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• 2013

Various voltage-gated $K^+$ currents were recently described in dorsal root ganglion (DRG) neurons. However, the characterization and diversity of voltage-gated $K^+$ currents have not been well studied in trigeminal root ganglion (TRG) neurons, which are similar to the DRG neurons in terms of physiological roles and anatomy. This study was aimed to investigate the characteristics and diversity of voltage-gated $K^+$ currents in acutely isolated TRG neurons of rat using whole cell patch clamp techniques. The first type (type I) had a rapid, transient outward current ($I_A$) with the largest current size having a slow inactivation rate and a sustained delayed rectifier outward current ($I_K$) that was small in size having a fast inactivation rate. The $I_A$ currents of this type were mostly blocked by TEA and 4-AP, K channel blockers whereas the $I_K$ current was inhibited by TEA but not by 4-AP. The second type had a large $I_A$ current with a slow inactivation rate and a medium size-sustained delayed $I_K$ current with a slow inactivation rate. In this second type (type II), the sensitivities of the $I_A$ or $I_K$ current by TEA and 4-AP were similar to those of the type I. The third type (type III) had a medium sized $I_A$ current with a fast inactivation rate and a large sustained $I_K$ current with the slow inactivation rate. In type III current, TEA decreased both $I_A$ and $I_K$ but 4-AP only blocked $I_A$ current. The fourth type (type IV) had a smallest $I_A$ with a fast inactivation rate and a large $I_K$ current with a slow inactivation rate. TEA or 4-AP similarly decreased the $I_A$ but the $I_K$ was only blocked by 4-AP. These findings suggest that at least four different voltage-gated $K^+$ currents in biophysical and pharmacological properties exist in the TRG neurons of rats.

• Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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• 2015.05a
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• pp.943-946
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• 2015

For myelination, Schwann cells and neuron cells from dorsal root ganglion (DRG) of rat embryos (E16) were cultured in vitro system. The purified DRG cells with anti-mitotic agents and purified Schwann cells were cocultured and then accomplished myelination processing. Treatment of M. leprae-specific phenolic glycolipid-1 (PGL-1) into this coculture system was performed and then accomplished demyelination. Therefore, we identified demyelination processing using antibody of myelin basic protein (MBP).

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.431-437
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• 2008

Sengmaek-san(Shengmai-san; SMS) is used in oriental medicine as one of the key herbal medicine for treating diverse symptoms including cardiovascular and neurological disorders. In the present study, the effects of SMS on axonal regeneration were investigated in the rat model given sciatic nerve injury. SMS treatment enhanced axonal regrowth into and the number of non-neuronal cells in the distal area after crush injury. GAP-43 protein levels were increased in the injured sciatic nerve compared to intact nerve and further upreguated by SMS treatment. GAP-43 protein was increased similarly in the dorsal root ganglion (DRG) at lumbar 4 - 6 by nerve injury and SMS treatment, suggesting GAP-43 induction at gene expression level. SMS-mediated increase in phospho-Erk1/2 protein was observed in the DRG as well as in the injured nerve implying its retrograde transport into the cell body as the process of lesion signal transmission. The present findings suggest that SMS may be involved in enhanced axonal regeneration via dynamic regulation of regeneration-associated proteins.

• Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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• 2015.10a
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• pp.830-833
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• 2015

Schwann cells and neuron cells from dorsal root ganglion (DRG) of rat embryos (E16) were isolated and purified in vitro system. The purified DRG cells with anti-mitotic agents and purified Schwann cells, respectively, were cocultured and then consummated myelination processing. This myelination system was treated by M. leprae-specific phenolic glycolipid-1 (PGL-1) and then accomplished demyelination system. We compared with myelination and demyelination using neurofilament of monoclonal antibody.

• The Korean Journal of Pain
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• v.20 no.2
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• pp.203-207
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• 2007

Inguinal hernia repair can result in paresthesia and/or pain in the inguinal region. Pharmacological and surgical management often yield inconsistent results associated with considerable risks and side effects. Radiofrequency thermocoagulation (RF) is a neuro-destructive treatment for severe pain, but associated with hypoesthesia, neuritis-like reactions, and occasional neuroma formation. Pulsed radiofrequency (PRF), unlike RF, delivers high intensity currents in pulses, is non-neurodestructive, and therefore less painful, without the potential complications. Here we report on PRF in chronic postoperative inguinal pain. A 23-year-old male who received right inguinal hernia repair and complained of right sided groin pain for approximately 10 years underwent PRF at the L1 and L2 dorsal root ganglia (DRG). He then reported a decrease in pain from 80-90/100 mm to 15-30/100 mm on a visual analogue scale (VAS), which lasted for twelve months.

• The Korean Journal of Pain
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• v.27 no.4
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• pp.326-333
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• 2014

Background: Nefopam is a centrally acting non-opioid analgesic agent. Its analgesic properties may be related to the inhibitions of monoamine reuptake and the N-methyl-D-aspartate (NMDA) receptor. The antinociceptive effect of nefopam has been shown in animal models of acute and chronic pain and in humans. However, the effect of nefopam on diabetic neuropathic pain is unclear. Therefore, we investigated the preventive effect of nefopam on diabetic neuropathic pain induced by streptozotocin (STZ) in rats. Methods: Pretreatment with nefopam (30 mg/kg) was performed intraperitoneally 30 min prior to an intraperitoneal injection of STZ (60 mg/kg). Mechanical and cold allodynia were tested before, and 1 to 4 weeks after drug administration. Thermal hyperalgesia was also investigated. In addition, the transient receptor potential ankyrin 1 (TRPA1) and TRP melastatin 8 (TRPM8) expression levels in the dorsal root ganglion (DRG) were evaluated. Results: Pretreatment with nefopam significantly inhibited STZ-induced mechanical and cold allodynia, but not thermal hyperalgesia. The STZ injection increased TRPM8, but not TRPA1, expression levels in DRG neurons. Pretreatment with nefopam decreased STZ-induced TRPM8 expression levels in the DRG. Conclusions: These results demonstrate that a nefopam pretreatment has strong antiallodynic effects on STZ-induced diabetic rats, which may be associated with TRPM8 located in the DRG.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.1
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• pp.1-16
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• 2004

The use of artificial nerve conduit containing viable Schwann cells is one of the most promising strategies to repair the peripheral nerve injury. To fabricate an effective nerve conduit whose microstructure and internal environment are more favorable in the nerve regeneration than existing ones, a new three-dimensional Schwann cell culture technique using $Matrigel^{(R)}$. and dorsal root ganglion (DRG) was developed. Nerve conduit of three-dimensionally arranged Schwann cells was fabricated using direct seeding of freshly harvested DRG into a $Matrigel^{(R)}$ filled silicone tube (I.D. 1.98 mm, 14 mm length) and in vitro rafting culture for 2 weeks. The nerve regeneration efficacy of three-dimensionally cultured Schwann cell conduit (3D conduit group, n=6) was assessed using SD rat sciatic nerve defect of 10 mm, and compared with that of silicone conduit filled with $Matrigel^{(R)}$ and Schwann cells prepared from the conventional plain culture method (2D conduit group, n=6). After 12 weeks, sciatic function was evaluated with sciatic function index (SFI) and gait analysis, and histomorphology of nerve conduit and the innervated tissues of sciatic nerve were examined using image analyzer and electromicroscopic methods. The SFI and ankle stance angle (ASA) in the functional evaluation were $-60.1{\pm}13.9$, $37.9^{\circ}{\pm}5.4^{\circ}$ in 3D conduit group (n=5) and $-87.0{\pm}12.9$, $32.2^{\circ}{\pm}4.8^{\circ}$ in 2D conduit group (n=4), respectively. And the myelinated axon was $44.91%{\pm}0.13%$ in 3D conduit group and $13.05%{\pm}1.95%$ in 2D conduit group to the sham group. In the TEM study, 3D conduit group showed more abundant myelinated nerve fibers with well organized and thickened extracellular collagen than 2D conduit group, and gastrocnemius muscle and biceps femoris tendon in 3D conduit group were less atrophied and showed decreased fibrosis with less fatty infiltration than 2D conduit group. In conclusion, new three-dimensional Schwann cell culture technique was established, and nerve conduit fabricated using this technique showed much improved nerve regeneration capacity than the silicone tube filled with $Matrigel^{(R)}$ and Schwann cells prepared from the conventional plain culture method.