• The Korean Journal of Pain
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• 제19권2호
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• pp.131-136
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• 2006

Background: The aim of this study was to clarify the role of spinal groups II and III metabotropic glutamate receptors (mGluRs) with respect to postoperative pain at the spinal level. In addition, the nature of the pharmacological interaction between groups II and III mGluRs agonists and morphine was determined. Methods: Catheters were inserted into the intrathecal space of male SD rats. To induce postoperative pain, an incision was made in the plantar surface of the hind paw. A pharmacological characteristic for the interaction between groups II and III mGluRs agonists and morphine was evaluated using a fixed-dose analysis. Results: None of intrathecal group II and III mGluRs agonists modified the withdrawal threshold of the incisional pain. The administration of intrathecal morphine resulted in an increase of a dose dependent withdrawal threshold. A fixed-dose analysis revealed that the group III mGluRs agonist, ACPT-III, increased the antinociceptive action of morphine, while the group II mGluRs agonist, APDC, had no effect the antinociception of morphine. Conclusions: These results suggest that group II and III mGluRs may not play a direct modulatory role in the processing of postoperative pain at the spinal level. However, agonizing group III mGluRs may indirectly contributable to the potentiation of morphines antinociception in the spinal cord. Thus, the combination of morphine and a group III mGluRs agonist may be useful in the management of spinal postoperative pain.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.647-655
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• 1997

The purpose of present study is to investigate the influence of a spinal gamma-aminobutyric acid B($GABA_B$) receptor on a central regulation of blood pressure(BP) and heart rate(HR), and to define its mechanism in the spinal cord. In urethane-anesthetized, d-tubocurarine-paralyzed and artificially ventilated male Sprague-Dawley rats, intrathecal administration of drugs were carried out using injection cannula(33-gauge stainless steel) through the guide cannula(PE 10) which was inserted intrathecally at lower thoracic level through the puncture of a atlantooccipital membrane. Intrathecal injection of an $GABA_B$ receptor agonist, baclofen(30, 60, 100 nmol) decreased both BP and HR dose-dependently. Pretreatment with 8-bromo-cAMP(50 nmol), a cAMP analog, or glipizide(50 nmol), a ATP-sensitive $K^+$ channel blocker, attenuated the depressor and bradycardic effects of baclofen(100 nmol), but not with 8-bromo-cGMP(50 nmol), a cGMP analog. These results suggest that the $GABA_B$ receptor in the spinal cord plays an inhibitory role in central cardiovascular regulation and that this depressor and bradycardic actions are mediated by the decrease of cAMP via the inhibition of adenylate cyclase and the opening of $K^+$ channel.

• Biomolecules & Therapeutics
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• 제14권2호
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• pp.119-124
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• 2006

This study was performed to investigate the influence of the spinal adenosine $A_1$ receptors on the central regulation of blood pressure (BP) and heart rate (HR), and to define whether its mechanism is mediated by cyclic AMP (cAMP), cyclic GMP (cGMP) or potassium channel. Intrathecal (i.t.) administration of drugs at the thoracic level were performed in anesthetized, artificially ventilated male Sprague-Dawley rats. I.t. injection of adenosine $A_1$ receptor agonist, $N^6$-cyclohexyladenosine (CHA; 1, 5 and 10 nmol) produced dose dependent decrease of BP and HR and it was attenuated by pretreatment of 50 nmol of 8-cyclopentyl-1,3-dimethylxanthine, a specific adenosine $A_1$ receptor antagonist. Pretreatment with a cAMP analogue, 8-bromo-cAMP, also attenuated the depressor and bradycardiac effects of CHA (10 nmol), but not with cGMP analogue, 8-bromo-cGMP. Pretreatment with a ATP-sensitive potassium channel blocker, glipizide (20 nmol) also attenuated the depressor and bradycardiac effects of CHA (10 nmol). These results suggest that adenosine $A_1$ receptor in the spinal cord plays an inhibitory role in the central cardiovascular regulation and that this depressor and bradycardiac actions are mediated by cAMP and potassium channel.

• 대한방사선치료학회지
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• 제11권1호
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• pp.53-59
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• 1999

The aim of this study is to improve the accuracy of field placement and junction between adjacent fields and block shielding through the use of a computed tomography(CT) simulator and virtual simulation. The information was acquired by assessment of Alderson Rando phantom image using CT simulator (I.Q. Xtra - Picker), determination of each field by virtual fluoroscopy of voxel IQ workstation AcQsim and colored critical structures that were obtained by contouring in virtual simulation. And also using a coronal, sagittal and axial view can determine the field and adjacent field gap correctly without calculation during the procedure. With the treatment planning by using the Helax TMS 4.0, the dose in the junction among the adjacent fields and the spinal cord and cribriform plate of the critical structure was evaluated by the dose volume histogram. The pilot image of coronal and sagittal view took about 2minutes and 26minutes to get 100 images. Image translation to the virtual simulation workstation took about 6minutes. Contouring a critical structure such as cribriform plate, spinal cord using a virtual fluoroscopy were eligible to determine a correct field and shielding. The process took about 20 minutes. As the result of the Helax planning, the dose distribution in adjacent field junction was ideal, and the dose level shows almost 100 percentage in the dose volume histogram of the spinal cord and cribriform plate CT simulation can get a correct therapy area due to enhancement of critical structures such as spinal cord and cribriform plate. In addition, using a Spiral CT scanner can be saved a lot of time to plan a simulation therefore this function can reduce difficulties to keep the patient position without any movements to the patient, physician and radiotherapy technician.

• 대한방사선기술학회지:방사선기술과학
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• 제46권6호
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• pp.527-533
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• 2023

The purpose of this study is to evaluate the clinical risk of spinal radiosurgery by calculating the dose difference due to dose calculation algorithm and multi-leaf collimator positioning error. The images acquired by the CT simulator were recalculated by correcting the multi-leaf collimator position in the dose verification program created using MATLAB and applying stoichiometric calibration and Monte Carlo algorithm. With multi-leaf collimator positioning error, the clinical target volume (CTV) showed a dose difference of up to 13% in the dose delivered to the 95% volume, while the gross tumor volume (GTV) showed a dose difference of 9%. The average dose delivered to the total volume showed dose variation from -8.9% to 9% and -10.1% to 10.2% for GTV and CTV, respectively. The maximum dose delivered to the total volume of the spinal cord showed a dose difference from -14.2% to 19.6%, and the dose delivered to the 0.35 ㎤ volume showed a dose difference from -15.5% to 19.4%. In future research, automating the linkage between treatment planning systems and dose verification programs would be useful for spinal radiosurgery.

• The Korean Journal of Physiology and Pharmacology
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• 제19권2호
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• pp.125-130
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• 2015

Cholecystokinin is known to be involved in the modulation of nociception and to reduce the efficacy of morphine analgesia. This study investigated the effects of intrathecal administration of morphine and the cholecystokinin type B antagonist CI-988 on below-level neuropathic pain after spinal cord injury in rats. We also examined the interaction of morphine and CI-988 in the antinociceptive effect. Both morphine and CI-988 given individually increased the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner. The combination of ineffective doses of intrathecally administered CI-988 and morphine produced significant analgesic effects and the combination of effective doses resulted in analgesic effects that were greater than the sum of the individual effects of each drug. Thus, morphine showed a synergistic interaction with CI-988 for analgesia of central neuropathic pain.

• 약학회지
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• 제43권2호
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• pp.263-273
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• 1999

When glutamate was infected intrathecally, the result is similar to those produced by TPA injected. The involvement of protein kinase C (PKC) in the nociceptive responses in rat dorsal horn neurons of lumbar spinal cord was studied. In test with formalin, a PKC inhibitor (chelerythrine) inhibited dose-dependently the formalin-induced behavior response. Neomycin also inhibited it significantly. But, a PKC activator (12-O-tetradecanoylphorbol-13-ester, TPA) showed reverse effect. When gluatamate was injected intrathecally, we observed the result is smilar to those produced by TPA injection. On the other hand, intrathecal injection of glutamate induced thermal and mechanical hyperalgesia. In Tail-flick test, we examined the involvement of PKC on the glutamate-indeced thermal hyperalgesia. Chelerythrine showed an inhibitory effect and TPA enhanced thermal response. Glutamate decreased the mechanical threshold significantly. A pretreatment of chelerythrine and neomycin inhibited glutamate-induced mechanical hyperalgesia, but the effect of neomycin was not significant. TPA had little effect on the mechanical nociceptive response. These results suggest that the PKC activation through metabotropic receptor at postsynaptic region of spinal cord dorsal horn neurons may influence on the persistent nociception produced by chemical stimulation with formalin, thermal and mechanical hyperalgesia induced by glutamate.

• 약학회지
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• 제44권6호
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• pp.499-504
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• 2000

We previously demonstrated that 6-paradol, a compound structurally related to capsaicin, showed to produce prolonged analgesia in experimental animals. The effects of 6-paradol on the release of adenosine were investigated in the rat spinal cord synaptosomes by high performance liquid chromatography. In the presence of $Ca^{++}$, adenosine was released from synaptosomes of rat spinal cord by 6-paradol and capsaicin in a dose dependent manner. Nifedifine, L-type voltage sensitive calcium channel blocker, was found to be ineffective in releasing adenosine by $10\;{\mu}M$ 6-paradol. After exposure to $10\;{\mu}M$ capsazepine, a novel capsaicin selective antagonist, the level of adenosine evoked by $10\;{\mu}M$ 6-paradol was decreased by 75%, and that evoked by $10\;{\mu}M$ capsaicin was blocked completely. These results suggest that the analgesic effect of 6-paradol might be mediated by the vanilloid (capsaicin) sensitive pathway, or the direct binding to the vanilloid receptor.

• Journal of Korean Neurosurgical Society
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• 제29권9호
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• pp.1153-1160
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• 2000

Objectives : This study was undertaken to investigate the effect of noncompetitive NMDA receptor blocker, MK801 on motor recovery, SSEP and pathology in spinal cord injured rat. Methods : The effects of MK801 on neuronal function protection, SSEP, and pathology were measured on spinal cord injury rats which were divided into 6 groups according to dose, time of drug delivery and magnitude of injury. Spinal cord injury was made with the magnitude of 25gm-cm and 50gm-cm on 42 rats. BBB locomotor function test was performed to evaluate the motor power recovery in hindlimb for 2 weeks after injury. After motor function test was completed, SSEP was measured. Amplitude and latency of the P1, N1 peak was measured and compared between groups. Finally rats were sacrificed, and pathologic findings including measurement of area of necrotic cord were studied and compared between groups. Results : Motor recovery at 2 weeks was better in MK801 group comparing to saline control group. SSEP at 2 weeks showed no difference in N1, P1 latencies, but significantly greater amplitude in MK801 group, compared to saline control group. On light microscope, there was no specific histologic differences between experimental groups. The cystic necrotic area in coronal plane was measured and compared in each group. The necrotic area was significantly smaller in MK801 1mg/kg group(delivered after injury) than vehicle group. The necrotic area in MK801 5mg/kg group and MK801 1mg/kg group(delivered before injury) was smaller than vehicle group even though it was not statistically significant. Conclusion : From the above result, it is speculated that NMDA blocker, MK801 can improve impaired neuronal function in spinal cord injury.

• 한국방사선학회논문지
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• 제10권4호
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• pp.233-239
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• 2016

방사선 치료시 최근 많이 쓰이고 있는 IMRT, Tomotherapy, mArc(modulation arc therapy)의 치료법을 선량적인 측면에서 상호 비교하고자 한다. 비소세포성 폐암의 환자를 대상으로 하여 치료계획용적에 58.0 Gy를 처방선량을 기준으로 설정하였으며 주변 정상장기는 척수, 식도, 간을 설정 하였다. PTVmean는 mArc의 경우 57.60 Gy, Tomotherapy가 61.04 Gy, IMRT는 58.95 Gy이었다. 식도(Esophagus)의 평균선량은 mArc가 2.84 Gy였고, Tomotherapy가 5.14 Gy, IMRT가 1.84 Gy로 나타났다. 간(Liver)은 mArc는 19.44 Gy, Tomotherpy가 12.22 Gy, IMRT는 21.97 Gy이었고 척수(Spinal Cord)은 mArc 5.72 Gy, Tomotherapy가 7.08 Gy, IMRT는 6.15 Gy로 측정되었다. 또한, 선량포함도와 선량체적곡선 등의 자료를 관찰해 본 결과 mArc와 Tomotherapy 그리고 IMRT의 결과와 현저한 차이를 보이지는 않았다. 하지만, 본 연구는 폐암이라는 질환으로 한정하였었고 실험군의 수가 적은 단점을 가지고 있으므로 좀 더 많은 질환과 환자를 대상으로 연구를 폭넓게 진행 한다면 환자 맞춤형 치료기법을 개발하여 적용될 것으로 사료된다.