• Journal of Korean Neurosurgical Society
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• v.58 no.3
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• pp.242-247
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• 2015

Objective : The purpose of this study is to determine whether the changes of contralateral sensorimotor cortical activation on functional magnetic resonance imaging (fMRI) can predict the neurological outcome among spinal cord injury (SCI) patients when the great toes are stimulated without notice. Methods : This study enrolled a total of 49 patients with SCI and investigated each patient's preoperative fMRI, postoperative fMRI, American Spinal Injury Association (ASIA) score, and neuropathic pain occurrence. Patients were classified into 3 groups according to the change of blood oxygenation level dependent (BOLD) response on perioperative fMRI during proprioceptive stimulation with repetitive passive toe movements : 1) patients with a response of contralateral sensorimotor cortical activation in fMRI were categorized; 2) patients with a response in other regions; and 3) patients with no response. Correlation between the result of fMRI and each parameter was analyzed. Results : In fMRI data, ASIA score was likely to show greater improvement in patients in group A compared to those belonging to group B or C (p<0.001). No statistical significance was observed between the result of fMRI and neuropathic pain (p=0.709). However, increase in neuropathic pain in response to the signal change of the ipsilateral frontal lobe on fMRI was statistically significant (p=0.030). Conclusion : When there was change of BOLD response at the contralateral sensorimotor cortex on perioperative fMRI after surgery, relief of neurological symptoms was highly likely for traumatic SCI patients. In addition, development of neuropathic pain was likely to occur when there was change of BOLD response at ipsilateral frontal lobe.

• International Journal of Oral Biology
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• v.45 no.3
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• pp.84-91
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• 2020

The present study investigated the participation of D-serine and NR2 in antinociception produced by blockade of central erythropoietin-producing hepatocellular carcinoma (Eph) A4 (EphA4) signaling in rats with trigeminal neuropathic pain. Trigeminal neuropathic pain was modeled in male Sprague-Dawley rats using mal-positioned dental implants. The left mandibular second molar was extracted under anesthesia, and a miniature dental implant was placed to induce injury to the inferior alveolar nerve. Our current findings showed that nerve injury induced by malpositioned dental implants significantly produced mechanical allodynia; additionally, the inferior alveolar nerve injury increased the expression of D-serine and NR2 subunits in the ipsilateral medullary dorsal horn (trigeminal subnucleus caudalis). Intracisternal administration of EphA4-Fc, an EphA4 inhibitor, inhibited nerve injury-induced mechanical allodynia and upregulated the expression of D-serine and NR2 subunits. Moreover, intracisternal administration of D-amino acids oxidase, a D-serine inhibitor, inhibited trigeminal mechanical allodynia. These results show that D-serine and NR2 subunit pathways participate in central EphA4 signaling after an inferior alveolar nerve injury. Therefore, blockade of D-serine and NR2 subunit pathways in central EphA4 signaling provides a new therapeutic target for the treatment of trigeminal neuropathic pain.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.1
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• pp.35-42
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• 2018

TRPA1 and TRPV1 are members of the TRP superfamily of structurally related, nonselective cation channels. TRPA1 and TRPV1 are often co-expressed in sensory neurons and play an important role in mechanical hyperalgesia and allodynia during neuropathic pain. Scutellariae Radix was reported to possess anti-inflammation properties and similar patterns of therapeutic action against different diseases. also Baicalin(a known principal constituent of Scutellaria Radix) was shown to down-regulate the mRNA expression levels of TRPV1. In this study, we observed the effects of Scutellariae Radix extract(SRE) in neuropathic pain induced SD rats via modulation of TRPV1 and TRPA1. Oral administration of a Scutellaria Radix extract(in doses of 300mg/kg, SRE(300)) showed a meaningful increase in the withdrawal threshold of mechanical allodynia and showed a meaningful decrease in the expression of c-fos compared to the control group. SRE(100) and SRE(300) showed a meaningful decrease in the expression of TRPV1 level compared to the control group. These results suggest that Scutellariae Radix extract could decrease mechanical allodynia by down-regulate the TRPV1 on the model of neuropathic pain.

• Journal of Pharmacopuncture
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• v.23 no.1
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• pp.30-36
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• 2020

Objectives: The objective of the study was to prepare Bauhinia variegata loaded nanoemulsion(formulation and determine the efficacy of herbal drug formulation against diabetic peripheral neuropathic pain through acupuncture technique. Methods: Nine different ba tches of nanoemulsion (NE1 NE9) of BVN was prepared by varying the S_mix ratio and the concentration of oil. BVN was characterized to determine particle size, shape, zeta potential, polydispersity index, optical transmittance, drug release profile and stora ge stability. The optimized formulation was subjected to plantar test, behavioral tests of neuropathic pain and Von Frey filament stimulation test. Diabetes was induced by intraperitoneal injection of freshly prepared solution of Streptozotocin (60 mg/kg) to the experimental rats. Animals were made diabetic divided into four groups, Group I was untreated normal control group, Group II was diabetic control group, Group III was Bauhinia variegata extract ( treated group (100 mg/kg/day, p.o) and Group IV was BVN treated groups (100 mg/kg/day, p.o) acute and chronically. Results: The prepared B. variegata loaded nanoemulsion was nanosized (124 nm), spherical, uniform and stable over the period of 180 days with no change in physiochemical properties. The bl ood glucose and body weight of animals was normalizing after four weeks of treatment that was significant with BVN in comparison to diabetic control group. The chronic administration of BVN significantly (P<0.001) decreased hind paw withdrawal latency an d attenuated mechanical allodynia as compared with diabetic rats. Conclusion: Thus, BVN may be an effective drug formulation against diabetic peripheral neuropathic pain.

• The Korean Journal of Pain
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• v.21 no.3
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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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• v.35 no.4
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• pp.413-422
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• 2022

Background: The neocortex, including the medial prefrontal cortex (mPFC), contains many neurons expressing nitric oxide synthase (NOS). In addition, increasing evidence shows that the nitric oxide (NO) and opioid systems interact in the brain. However, there have been no studies on the interaction of the opioid and NO systems in the mPFC. The objective of this study was to investigate the effects of administrating L-arginine (L-Arg, a precursor of NO) and N(gamma)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NOS) into the mPFC for neuropathic pain in rats. Also, we used selective opioid receptor antagonists to clarify the possible participation of the opioid mechanism. Methods: Complete transection of the peroneal and tibial branches of the sciatic nerve was applied to induce neuropathic pain, and seven days later, the mPFC was cannulated bilaterally. The paw withdrawal threshold fifty percent (50% PWT) was recorded on the 14th day. Results: Microinjection of L-Arg (2.87, 11.5 and 45.92 nmol per 0.25 µL) increased 50% PWT. L-NAME (17.15 nmol per 0.25 µL) and naloxonazine (an antagonist of mu opioid receptors, 1.54 nmol per 0.25 µL) inhibited anti-allodynia induced by L-Arg (45.92 nmol per 0.25 µL). Naltrindole (a delta opioid receptor antagonist, 2.45 nmol per 0.25 µL) and nor-binaltorphimine (a kappa opioid receptor antagonist, 1.36 nmol per 0.25 µL) were unable to prevent L-Arg (45.92 nmol per 0.25 µL)-induced antiallodynia. Conclusions: Our results indicate that the NO system in the mPFC regulates neuropathic pain. Mu opioid receptors of this area might participate in pain relief caused by L-Arg.

• The Korean Journal of Pain
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• v.27 no.2
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• pp.174-177
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• 2014

Glomus tumors are a rare, benign neoplasm and 75% exist in the subungual region. Extradigital glomus tumors are much more difficult to diagnose because of their atypical location and symptoms. Furthermore, if their symptoms are similar to neuropathic pain, the patient can suffer from misdirected treatment due to misdiagnosis. It is essential to perform careful evaluation of the lesion itself in order to reduce misdiagnosis. Ultrasonography is a useful, non-invasive method that can be easily performed in the pain clinic for local evaluation and diagnosis. We report a case of misdiagnosed glomus tumor in the thigh which was properly diagnosed after ultrasonography.

• Journal of Acupuncture Research
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• v.30 no.3
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• pp.125-134
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• 2013

Objectives : We studied the effects of electro and laser acupuncture treatment with $GB_{39}$ and $GB_{34}$ on neuropathic pain in rats induced by tibial and sural nerve ligation. Methods : To produce the model of neuropathic pain, the tibial and sural nerves of rats were ligated by a 6-0 silk thread. Three days after the neuropathic surgery, only electro acupuncture(EA), electro acupuncture and 830 nm laser acupuncture(EA-LA-1), and electro acupuncture and 904 nm laser acupuncture(EA-LA-2) were treated with $GB_{39}$ and $GB_{34}$ twice a week for 8 weeks. We observed the withdrawal response of neuropathic rats' legs by von Frey filament and acetone stimulation. We also observed c-fos and nocieptin on the central gray area in the midbrain of neuropathic rats. Results : As we observed the effect of mechanical allodynia, the EA and EA-LA-1 groups in 5 and 6 weeks and the EA-LA-2 group in 6 weeks increased significantly compared with the control group. As for the effect of c-fos activity in the central gray region, the EA, EA-LA-1, and EA-LA-2 groups decreased significantly compared with the control group. The EA-LA-2 group increased significantly compared with the control group as regards the effect of nociceptin activity in the central gray region. Conclusions : We noticed the synergic effect of electro and laser acupuncture treatment because the EA-LA-1 and EA-LA-2 groups had more controllable effect compared with the control group. This study can be used in clinical therapy for neuropathic pain.

• The Korean Journal of Pain
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• v.21 no.3
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• pp.179-186
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• 2008

Background: The adrenergic nervous system in the spinal cord contributes to the development of neuropathic pain after nerve injury. Brain derived neurotrophic factor may facilitate the sympathetic change in the spinal cord and influence the state of neuropathic pain. We probed the effect of chronic repetitive administration of systemic 4-methylcatechol, which is known to be a neurotrophic factor inducer, in a spinal nerve ligation model. Methods: We made the rat neuropathic pain model by the ligation of the L5 spinal nerve. Intraperitoneal 4-methylcatechol ($10{\mu}g/kg$) or the same volume of saline wasadministrated twice daily just after the operation for 7 days. The tactile allodynia was measured by using von Frey filaments and its change was followed up from 3 days after SNL. The lumbosacral enlargement of the spinal cord was taken out and the mRNA contents of the ${\alpha}_2-adrenoceptor$ subtypes were measured by real time polymerase chain reaction and this was then compared with the control groups. The antiallodynic effect of intrathecal clonidine (3, 10, $30{\mu}g$) was evaluated and compared in the 4-methylcatechol treated rats and the control rats. Results: The expression of the ${\alpha}_{2A}$ and ${\alpha}_{2C}$ adrenoceptor subtypes did not change after 4-methylcatechol treatment. Intrathecal clonidine showed an earlier and better effect at the highest dose ($30{\mu}g$ intrathecal), but not with any other doses. Conclusions: Chronic intraperitoneal administration of 4-methylcatechol may improve the effect of intrathecal clonidine, but we could not prove the increase of ${\alpha}_{2A}$ and ${\alpha}_{2C}$ adrenoceptors in the spinal cord of 4-methylcatechol treated rats.

• The Korean Journal of Pain
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• v.22 no.1
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• pp.21-27
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• 2009

Background: The neuropathic pain arising from nerve injury is difficult to treat and the therapeutic effects of opioid drugs remain debatable. Agonists acting at the ${\alpha}_2$ adrenergic and opioid receptors have analgesic properties and they act synergistically when co-administered in the spinal cord. The lack of subtype-selective pharmacological agents has previously impeded the synergistic effects that are mediated by the adrenergic receptor subtypes. Methods: We created neuropathic pain model by ligating the L5 spinal nerve in Sprague-Dawley rats (n = 18). We divided the rats into three groups (n = 6 for each group), and we administered intraperitoneal morphine (1 mg/kg, 3 mg/kg, 5 mg/kg) and then we measured the mechanical allodynia with using von-Frey filaments for 8 hours. We then injected morphine (5 mg/kg) intraperitoneally, twice a day for 2 weeks. We measured the tactile and cold allodynia in the morphine group (n = 9) and the saline group (n = 9). After 2 weeks, we decapitated the rats and harvested the spinal cords at the level of lumbar enlargement. We compared the ${\alpha}_2$ subtype mRNA expression with that of control group (n = 6) by performing real time polymerase chain reaction (RTPCR). Results: Intraperitoneal morphine reduced the neuropathic pain behavior in the dose-dependent manner. Chronic morphine administration showed an antiallodynic effect on the neuropathic pain rat model. The rats did not display tolerance or hyperalgesia. The expression of the mRNAs of the ${\alpha}_{2A}$, ${\alpha}_{2B}$, ${\alpha}_{2C}$ subtypes decreased, and morphine attenuated this effect. But we could not get statistically proven results. Conclusions: Systemic administration of morphine can attenuate allodynia during both the short-term and long-term time course. Morphine has an influence on the expression of ${\alpha}_2$ receptor subtype mRNA. Yet we need more research to determine the precise effect of morphine on the ${\alpha}_2$ subtype gene expression.