• The Korean Journal of Pain
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• v.28 no.3
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• pp.185-192
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• 2015

Background: Neuropathic pain is a global clinical problem; nevertheless, nerve injury treatment methods remain limited. Olanzapine has antinociceptive and anti-nueropathic properties; however, its preventive effects have not been assessed in nerve injury models. Methods: We prepared a partial sciatic nerve ligation (Seltzer model) or sham-operated model in male Sprague-Dawley rats under isoflurane anesthesia. In a pre-treatment study, we administered olanzapine (10 mg/kg) intraperitoneally 1 h before nerve ligation. In post-treatment and dose-dependent studies, we injected 3 different doses of olanzapine intraperitoneally 1 h after nerve ligation. Mechanical allodynia was measured before and 7 days after surgery. Immunohistochemical analysis using anti-Iba-1 antibody was used to assess the effect of olanzapine at the spinal level. Results: In the pre-treatment study, median withdrawal thresholds of the normal saline groups were significantly lower than those of the sham-operated groups; however, those of the olanzapine (10 mg/kg) and sham-operated groups were not different. In the post-treatment and dose-dependent studies, the median withdrawal thresholds of the olanzapine (2.5 mg/kg) and normal saline groups were not different; however, those of the olanzapine (10 and 50 mg/kg) groups were significantly higher than those of the normal saline groups. Olanzapine did not have a significant effect on the density of Iba-1 staining. Conclusions: Olanzapine attenuated mechanical allodynia dose-dependently in the Seltzer model. This anti-allodynic effect of olanzapine was observed even when injected 1 h after nerve ligation. This effect of olanzapine appeared to be unrelated to microglia activation in the ipsilateral dorsal horn of the lumbar spinal cord.

• Journal of the Korean Society of Radiology
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• v.6 no.5
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• pp.365-371
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• 2012

The radiation therapy treatment technique is developed from 3D-CRT, IMRT to Tomotherapy. and these three technique was most widely using methods. We find out a comparison normal tissue doses and tumor dose of 3D-CRT, IMRT(Linac Based), and Tomotherapy on Head and Neck Cancer. We achieved radiological image used the Human model phantom (Anthropomorphic Phantom) and it was taken CT simulation (Slice Thickness : 3mm) and GTV was nasopharngeal region and PTV(including set-up margin) was GTV plus 2mm area. and transfer those images to the radiation planning system (3D-CRT - ADAC-Pinnacle3, Tomotherapy - Tomotherapy Hi-Art System). The prescription dose was 7020 cGy and measuring PTV's dose and nomal tissue (parotid gland, oral cavity, spinal cord). The PTV's doses was Tomotherapy, Linac Based - IMRT, 3D-CRT was 6923 cGy, 6901 cGy and 6718 cGy its dose value was meet TCP because its value was up to the 95% based on 7020 cGy, Nomal tissue (parotid gland, oral cavity, spinal cord) was 1966 cGy(Tomotherapy), 2405 cGy(IMRT), 2468 cGy(3D-CRT)[parotid gland], 2991 cGy(Tomotherapy), 3062 cGy(IMRT), 3684 cGy (3D-CRT)[oral cavity], 1768 cGy(Tomotherapy), 2151 cGy(IMRT), 4031 cGy(3D-CRT)[spinal cord] its value did not exceeded NTCP. All the treatment techniques are equated with tumor and nomal tissue doses. The 3D-CRT was worse than other techniques on dose distribution, but it is reasonable in terms of TCP and NTCP baseline Tomotherapy, IMRT -dose distribution was relatively superior- was hard to therapy to claustrophobic patients and patients with respiratory failure. Particularly, in case on Tomotherapy, it take MVCT before treatment so dose measurement will be unnecessary radiation exposure to patients. Conclusion, Tomotherapy was the best treatment technique and 2nd was IMRT, and 3rd 3D-CRT. But applicable differently depending on the the patient's condition even though dose not matter.

• The Journal of the Korean bone and joint tumor society
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• v.13 no.1
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• pp.14-21
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• 2007

Bone is a common site for metastatic spread from many kinds of malignancies. The morbidity associated with this metastatic spread can be significant, including severe pain. When it comes to spinal metastasis, occupying nearly 40% of skeletal metastases, the risks of complications, such as vertebral body collapse, nerve root impingement, or spinal cord compression, are also significant. Because of the necessity of preserving the integrity of the spinal column and the proximity of critical structures, surgical treatment has limitations when durable local control is desired. Radiotherapy, therefore, is often used as an adjunct treatment or as a sole treatment. A considerable limitation of standard radiotherapy is the reported recurrence rate or ineffective palliation of pain, either clinically or symptomatically. This may be due to limited radiation doses to tumor itself because of the proximity of critical structures. CyberKnife is an image-guided robotic radiosurgical system. The image guidance system includes a kilovoltage X-ray imaging source and amorphous silica detectors. The radiation delivery device is a mobile X-band linear accelerator (6 MV) mounted on a robotic arm. Highly conformal fields and hypofractionated radiotherapy schedules are increasingly being used as a means to achieve biologic dose escalation for body tumors. Therefore, we can give much higher doses to the targeted tumor volume with minimizing doses to the surrounding critical structures, resulting in more effective local control and less severe side effects, compared to conventional fractionated radiotherapy. A description of this technology and a review of clinical applications to bone metastases are detailed herein.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.294-294
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• 1994

To investigate analgesic mechanism of capsaicin and its analogues (capsaicinoids), release of adenosine was measured by high performance liquid chromatography from dorsal spinal cord synaptosomes, Exposure of synaptosomes to K$\^$+/ and morphine produced a dose dependent release of adenosine in the presence of Ca$\^$++/. Capsaicin (0.1, 1, 10 M), and its analogues 6-paradol (1, 10 M), NE-19550 (1, 10, 100 M), DMNE (1, 10, 100 M) and KR 25018 (0.1, 1, 10 M) produced a dose dependent release of adenosine in the presence of Ca$\^$++/. Nifedipine, L-type voltage sensitive calcium channel blocker, inhibited K$\^$+/ (6, 12 mM)- and morphine (10 M)-evoked release of adenosine completely, but inhibited capsaicin, and capsaicinoids-evoked release of adenosine partially. Capsazepine, a novel capsaicin select ive antagonist, blocked only capsaicin and capsaicinoids induced release of adenosine. Therefore, the adenosine release by capsaicin and capsaicinoids having antinociceptive effects involve activation of capsaicin specific receptor and capsaicin sensitive Ca$\^$++/ channel.

• Journal of Chest Surgery
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• v.53 no.4
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• pp.184-190
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• 2020

Radiation therapy (RT) has improved patient outcomes, but treatment-related complication rates remain high. In the conventional 2-dimensional and 3-dimensional conformal RT (3D-CRT) era, there was little room for toxicity reduction because of the need to balance the estimated toxicity to organs at risk (OARs), derived from dose-volume histogram data for organs including the lung, heart, spinal cord, and liver, with the planning target volume (PTV) dose. Intensity-modulated RT (IMRT) is an advanced form of conformal RT that utilizes computer-controlled linear accelerators to deliver precise radiation doses to the PTV. The dosimetric advantages of IMRT enable better sparing of normal tissues and OARs than is possible with 3D-CRT. A major breakthrough in the treatment of esophageal cancer (EC), whether early or locally advanced, is the use of proton beam therapy (PBT). Protons deposit their highest dose of radiation at the tumor, while leaving none behind; the resulting effective dose reduction to healthy tissues and OARs considerably reduces acute and delayed RT-related toxicity. In recent studies, PBT has been found to alleviate severe lymphopenia resulting from combined chemo-radiation, opening up the possibility of reducing immune suppression, which might be associated with a poor prognosis in cases of locally advanced EC.

• Radiation Oncology Journal
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• v.28 no.4
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• pp.238-248
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• 2010

Purpose: To compare the dose distributions between three-dimensional (3D) and four-dimensional (4D) radiation treatment plans calculated by Ray-tracing or the Monte Carlo algorithm, and to highlight the difference of dose calculation between two algorithms for lung heterogeneity correction in lung cancers. Materials and Methods: Prospectively gated 4D CTs in seven patients were obtained with a Brilliance CT64-Channel scanner along with a respiratory bellows gating device. After 4D treatment planning with the Ray Tracing algorithm in Multiplan 3.5.1, a CyberKnife stereotactic radiotherapy planning system, 3D Ray Tracing, 3D and 4D Monte Carlo dose calculations were performed under the same beam conditions (same number, directions, monitor units of beams). The 3D plan was performed in a primary CT image setting corresponding to middle phase expiration (50%). Relative dose coverage, D95 of gross tumor volume and planning target volume, maximum doses of tumor, and the spinal cord were compared for each plan, taking into consideration the tumor location. Results: According to the Monte Carlo calculations, mean tumor volume coverage of the 4D plans was 4.4% higher than the 3D plans when tumors were located in the lower lobes of the lung, but were 4.6% lower when tumors were located in the upper lobes of the lung. Similarly, the D95 of 4D plans was 4.8% higher than 3D plans when tumors were located in the lower lobes of lung, but was 1.7% lower when tumors were located in the upper lobes of lung. This tendency was also observed at the maximum dose of the spinal cord. Lastly, a 30% reduction in the PTV volume coverage was observed for the Monte Carlo calculation compared with the Ray-tracing calculation. Conclusion: 3D and 4D robotic radiotherapy treatment plans for lung cancers were compared according to a dosimetric viewpoint for a tumor and the spinal cord. The difference of tumor dose distributions between 3D and 4D treatment plans was only significant when large tumor movement and deformation was suspected. Therefore, 4D treatment planning is only necessary for large tumor motion and deformation. However, a Monte Carlo calculation is always necessary, independent of tumor motion in the lung.

• The Journal of Korean Society for Radiation Therapy
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• v.34
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• pp.51-60
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• 2022

Objectives: The purpose is to evaluate dosimetric performance and delivery efficiency of VMAT with Halcyon LINAC for double target spine SBRT Materials and Methods: 12 patients with spine oligometastases were retrospectively studied. Single-isocenter spine SBRT plans was established using Halcyon® with Dual Layer MLC and Truebeam® with High Definition MLC. All patients' plans were created in Eclipse TPS through the identical conditions and optimization. C.I, H.I, G.I (Gradient Index), maximal and volumetric doses to spinal cord and low dose area were evaluated for comparison of both plans. Also, total MU and BOT(Beam On Time) were evaluated. Results: Halcyon plans was no Statistical differences in C.I and H.I. However, the average of G.I was 4.64 for Halcyon, which decreased to 5.5% compared to Truebeam (P<0.001). Halcyon plans demonstrated statistically significant reduced G.I. The average of 50% and 25% isodose volume was 487.56 cc (-3.82%, P<0.001), 1859.45 cc (-4.75%, P<0.001) in Halcyon, respectively. Significantly reduced low dose spill were observed in Halcyon plans. In the evaluation of the spinal cord, the average of Dmean and V10 of Halcyon plans in the sample group with an overlap volume of less than 1 cc was 6.802 Gy (-3.504%, P=0.067), 5.766±1.683 cc (-8.199%, P=0.002), respectively. Halcyon plans demonstrated statistically significant reduced D_mean and V10. For delivery efficiency, MU and BOT(maximum dose rate for each machine), on average, increased in Halcyon plans. However, the average of BOT(800MU/min for each machine) was 648.33 sec for Halcyon (-1.74%, P<0.001). Conclusion: Halcyon plan for double-target spine SBRT demonstrated advantages in the low dose area with a steep dose gradient, while having dosimetrically equivalent target dose distribution and spinal cord protective effect. As a result, Halcyon LINAC produced a dosimetrically improved plan for double-target spine SBRT.

• The Korean Journal of Pain
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• v.18 no.1
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• pp.1-9
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• 2005

Background: Spinal metabotropic glutamate receptors (mGluRs) and opioid receptors are involved in the modulation of nociception. Although opioid receptors agonists are active for pain, the effects of the compounds for the mGluRs have not been definitely investigated at the spinal level. We examined the effects of the intrathecal mGluR compounds and morphine in the nociceptive test, and then we further clarified the role of the spinal mGluRs. In addition, the nature of the pharmacological interaction after the coadministration of mGluRs compounds with morphine was determined. Methods: Catheters were inserted into the intrathecal space of male SD rats. For the induction of pain, $50{\mu}l$ of 5% formalin solution or a thermal stimulus was applied to the hindpaw. An isobolographic analysis was used for the evaluation of the drug interaction. Results: Neither group I mGluR compounds nor group III mGluR compounds produced any antinociceptive effect in the formalin test. The group II mGluR agonist (APDC) had little effect on the formalin-induced nociception. The group II mGluR antagonist (LY 341495) caused a dose-dependent suppression of the phase 2 flinching response on the formalin test, but it did not reduce the phase 1 response of the formalin test nor did it increase the withdrawal latency of the thermal stimulus. Isobolographic analysis revealed a synergistic interaction after the intrathecal delivery of a LY 341495-morphine mixture. Conclusions: These results suggest that group II mGluRs are involved in the facilitated processing at the spinal level, and the combination of LY 341495 with morphine may be useful to manage the facilitated pain state.

• The Korean Journal of Pain
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• v.18 no.2
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• pp.113-117
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• 2005

Background: Serotonin 3 receptor is involved in the modulation of nociceptive transmission in the spinal cord. The serotonin 3 receptor antagonist has been used for the management of opioid-induced nausea and vomiting. The aim of this study was to examine whether the analgesic effect of morphine is antagonized by serotonin 3 receptor antagonists at the spinal level. Methods: Rats were implanted with lumbar intrathecal catheters. For nociception, a formalin solution (5%, $50{\mu}l$) was injected into the hind paw of male Sprague-Dawley rats. To determine whether the effect of intrathecal morphine was mediated via serotonin 3 receptors, serotonin 3 receptor antagonists were intrathecally administered 10 min prior to the morphine delivery. Following the formalin injection, formalin-induced nociceptive behavior (flinching response) was observed for 60 min. Results: Intrathecal morphine produced a dose-dependent suppression of the flinches in both phases during the formalin test. The analgesic action of morphine was not reversed by serotonin 3 receptor antagonists (LY-278,584, ondansetron), which had little per se effect on the formalin-induced nociception. Conclusions: Spinal serotonin 3 receptors may not be involved in the analgesia of morphine on a nociceptive state evoked by a formalin stimulus.

• The Korean Journal of Pain
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• v.34 no.1
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• pp.58-65
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• 2021

Background: Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism. Methods: Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague-Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed. Results: Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine. Conclusions: These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.