• 대한약리학회지
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• 제20권2호
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• pp.15-21
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• 1984

Clonidine으로 고혈압을 치료시 부작용으로 진정작용이 심하게 나타나며 이는 Clonidine이 중추 ${\alpha}_2$-수용체를 흥분시켜서 일으킨 결과임이 보고되었다. 본 실험에서는 부화 $1{\sim}2$일이 된 병아리에 ${\alpha}_2$-수용체 효현제들을 주사하여 정좌반사가 소실될 때까지의 시간 및 수련시간을 관찰하였으며, 그리고 guanabenz 유도 수면에 대한 ${\alpha}_1$- 및 ${\alpha}_2$-수용체 길항제 및 opiate수용체 길항제가 어떻게 관여하는 지를 검토하고 다음과 같이 요약하였다. 1) ${\alpha}_2$-수용체 효현제중 guanabenz, clonidine, guanfacine 및 B-HT 933은 용량에 의존해서 정좌반사소실까지의 잠복시간을 감소시켰다. 그러나 B-HT 920 및 oxymetazoline은 잠복시간을 경미하게 연장시켰다. 2) ${\alpha}_2$-수용체 효현제들은 용량에 비례해서 수면시간을 증가시켰고 이들의 강도는 guanabenz>clonidine>oxymetazoline${\geq}$B-HT 933${\geq}$B-HT 920> guanfacine의 순위이었다. 3) ${\alpha}_2$-수용체 길항제들은 양에 비례해서 guanabenz 유도 수면시간을 감소시켰으며 이들의 강도는 yohimbine>rauwolscine>piperoxan${\geq}$RX 781094의 순위 이었다. 4) Ethanol 및 hexobarbital유도 수면은 yohimbine에 의해 봉쇄되지 아니하였다. 5) Guanabenz유도 수면시간에 대해서 ${\alpha}_1$-수용체 효현제인 methoxamine 및 Phenylephrine은 영향이 없었으나, ${\alpha}_1$-수용체 결항제인 Prazosin은 증가시켰다. 그러나 corynanthine은 반대로 수면시간을 현저히 감소시켰다. 이상의 결과로 보아 중추 ${\alpha}_2$-수용체의 흥분으로 병아리의 수면이 야기되고, 중추 ${\alpha}_1$-수용체의 역할에 대하여는 명백하지 않으나 ${\alpha}_2$-수용체 효현제 및 길항제의 성질을 규명하는 동물모델로서 부화 I${\sim}$2일의 병아리가 크게 유용할 것으로 시사되는 바이다.

• 대한약리학회지
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• 제30권1호
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• pp.11-18
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• 1994

Opioid수용체는 adenylate cyclase의 활성을 억제하므로써 cyclic AMP의 양을 감소시킨다. 본 연구에서는 striatum에서 dopamine과 opioid 신경전달계의 상호관계를 알아보고자 haloperidol(750ug/kg)을 10일간 복강내 투여하여 dopaminergic pathway를 차단시킨후 mouse striatum에서 선택적 opioid ${\mu},\;{\gamma}\;{\kappa}$ 수용체 agonist들에 의해 축적되는 cAMP양을 측정하여 본 결과, haloperidol단독투여에 의해서 cAMP는 유의한 증가를 나타내었으며, haloperidol 장기투여된 mouse striatum 에서 morphine(20mg/kg), DAGO(5Oug/kg), DPDPE(50ug/kg), U5O,488H (500ug/kg)투여에 의해서 haloperidol에 의한 cAMP 증가는 억제되었으며, 정상 mouse에 투여된 morphine, DAGO, DPDPE, U5O,488H에 비해서는 DAGO, DPDPE 투여군에서 증가를 나타내었다. Haloperidol장기투여로 인한 morphine, DAGO, DPDPE, U5O,488H의 영향은 naloxone에 의해서 morphine과 U5O, 488H투여군에서 길항되었으며 정상 mouse에 투여된 morphine, DAGO, DPDPE, U5O,488H에 의한 cAMP의 감소는 naloxone에 의하여 모든 실험군에서 길항되었다. 이상의 결과로 보아 dopaminergic denervation시 mouse striatum에서 ${\mu},\;{\gamma},\;{\kappa}$효현제에 의하여 축적되는 cAMP양은 ${\kappa}$수용체 효현제인 U5O,488H에서 가장 현저한 감소를 보여 각 수용체의 활성화정도는 변화되며, 그중에서 ${\kappa}$수용체는 그 기능이 가장 보존되고 있음을 알 수 있었다.

• 대한약리학회지
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• 제17권2호
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• pp.17-22
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• 1981

Guinea-pig ileum을 naloxone을 가(加)하거나 가(加)하지 않은 전해질(電解質) 농도(濃度)가 다른 modified Krebs-Henseleit bicarbonate buffer solution에 $4^{\circ}C$에서 24시간 incubation한 다음, morphine의 수축(收縮) 억제작용(抑制作用)으 관찰(觀察)하여 다음과 같은 성적(成績)을 얻었다. 1) Incubation 자체(自體)로써 morphine의 작용(作用) 강화(强化)되었다. 2) Incubation media 내(內) 전해질(電解質) 변동(變動)은 $Na^+\;75mM$ 군(群)과 $K^+2.9mM$ 군(群)에서는 morphine의 작용(作用)이 강화(强化)되었고, $Ca^{++}\;3.6mM$ 군(群), $Mg^{++}$ free 군(群)과 $Mn^{++}\;0.2mM$ 군(群)에서는 약화(弱化)되었다. 3) Incubation media내(內) naloxone은 morphine의 작용(作用)을 강화(强化)하였다. Incubation media 내(內) naloxone을 가(加)하고 전해질(電解質)을 변동(變動)시킨 실험(實驗)에서 $Na^+\;75mM$ 군(群), $K^+2.9mM$ 군(群)과 $Ca^{++}3.6mmM$ 군(群)에서는 naloxone에 의(依)하여 morphine 작용(作用)이 약화(弱化)되었고, $Mg^{++}$ free 군(群)과 $Mn^{++}\;0.2mM$ 군(群)에서는 강화(强化)되었다. 4) Naloxone에 대(對)한 $pA_2$치(値)는 전군(全群)에서 변동(變動)이 없었다. 5) 이상(以上) 실험성적(實驗成績)은 naloxone opiate receptor에 대(對)한 작용외(作用外)에 세포막 또는 근세포수축기구(筋細胞收縮機構)에 영향(影響)을 미처 morphine의 작용(作用)에 영향(影響)을 줄 수 있음을 시사(示唆)한다.

• The Korean Journal of Pain
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• 제9권1호
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• pp.151-158
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• 1996

Background: Buprenorphine, a new synthetic thebaine derivative, is a partial agonist of the opioid $\mu$-receptor with high receptor affinity, great lipid solubility, and slow rate of opiate receptor association and dissociation. Continuous epidural infusion of opioid can possibly produced undesirable effects, such as respiratory depression, pruritus, etc, in spite of effective postoperative analgesia. Methods: The present study was undertaken to compare the analgesic properties and side effects of continuous epidural infusion of buprenorphine combined with bupivacaine, and morphine combined with bupivacaine in 90 patients following elective gynecologic lower abdominal surgery. At the end of surgery, the initial bolus doses were 3 mg morphine (M group), 0.15 mg buprenorphine (0.15B group), 0.3 mg buprenorphine (0.3B group) combined with 0.25% bupivacaine 10ml, and subsequent continuous infusion doses were 6 mg morphine plus 0.125% bupivacine 100 ml (M group) and 0.6mg buprenorphine plus 0.125% bupivacaine 100 ml (0.15B, 0.3B, group) during 48 hours. The assessment of analgesic efficacy and side effects were made at arrival of recovery room, 1 hr, 4 hr, 8 hr, 24 hr, 36 hr, and 48 hr after the epidural injection. Results: The pain score during 48 hours was significantly higher in the 0.15B group than in the M group and 0.3B group (P<0.05), and the number of patients requiring additional analgesics was significantly higher in the 0.15B group than in the M group and 0.3B group (P<0.05). Signs of respiratory depression were not noted, and the incidence of pruritus, nausea, and vomiting was slightly lower in the 0.15B group and 0.3B group than in the M group, and the incidence of sedation and urinary retention was similar in three group. The subjective rating of satisfaction was better in the 0.3B group than in the M group and 0.15B group (P<0.05). Conclusion: The above results suggest that continuous epidural infusion of buprenorphine combined with low-dose bupivacaine is an advisable method of postoperative analgesia.

• The Korean Journal of Pain
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• 제1권1호
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• pp.53-58
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• 1988

암으로 인하여 상하복부 및 하지에 심한 통증을 호소하는 환자에게 지주막하강 및 경막외강에 각각 미량의 몰핀을 지속적으로 주입하여 진통효과를 얻은 바 진통효과 발현시간은 지주막 하강 투여군이 빨랐고 지속시간 별로는 큰 차이가 없었고 제통효과 면에서는 지주막하강 투여 군이 더욱 확실하였고, 지속적 몰핀 주입에 의한 내성발현 정도는 경악의장 투여군이 심하였고 합병증 발현정도로는 경막외강 투여군이 경미하였음을 봐서 내성발생문제를 앞으로 해결한 다면 장기간 몰핀 등 마약성 약물을 투여해야되는 암성통증환자에서는 경막외강 투여법이 지주막하강 투여법보다 안전한 제통방법으로 사료된다.

• The Korean Journal of Pain
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• 제8권2호
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• pp.235-243
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• 1995

A retrospective study was performed to evaluate the effects, and side effects, of epidural analgesia for postoperative pain relief of 2,381 surgical patients who received general-epidural, or epidural anesthesia only. Anesthesia records, patients charts, and pain control records were reviewed and classified according to: age, sex, body weight, department, operation site, epidural puncture site, degree of pain relief by injection mode & epidural injectate, and side effects(including nausea, vomiting, pruritus, urinary retention and respiratory depression). The results were as follows: 1) From the total of 2,381 patients, there were 1,563(66%) female patients; 1.032(43%) patients were from Obstetrics and Gynecology. 2) Lower abdomen, thorax, lower extremity and upper abdomen in the operation site; and lumbar, upper, lower thoracic in puncture site were order of decreasing frequency. Length of epidural injection for pain relief averaged $1.72{\pm}1.02$ days. 3) Ninety three percent of the patients experienced mild or no pain in the postoperative course. Analgesic quality was not affected by the kind of epidural injectate. 4) Nausea occurred in 3.2% of all patients, vomiting in 1.1%, pruritus 0.9%, urinary retention 0.6%, respiratory depression 0.08%. 5) Frequency of nausea was higher with female patients compared to male patients(p<0.05). 6) Pruritus frequency was higher with male patients than female patients(p<0.05); and more frequent with patients who received epidural injection with morphine than patients who received epidural injection without morphine(p<0.01). 7) Urinary retention was higher in female patients, and more frequent with patients who had received epidural injection with morphine than epidural injection without morphine(p<0.05). 8) There were two cases of respiratory depression. The course of treatment consisted of: cessation of epidural infusion, then administration of oxygen and intravenous naloxone. We conclude that postoperative epidural analgesia with a combination of local anesthetics and opiate is and effective method for postoperative pain relief with low incidence of side effects. However, patients should be carefully evaluated as rare but severe complications of respiratory depression may ensue.

• Journal of Acupuncture Research
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• 제22권3호
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• pp.23-35
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• 2005

본 연구에서는 전침자극이 면역계의 THl/TH2 분화평형에 미치는 영향과 opioid system 과의 관계를 알아보고자 DNP-KLH의 자극을 통해 IgE 매개 알러지 반응모델을 구축하고 족삼리(足三里).에 전침자극을 가한 후 TH1/TH2 분화평형 및 opioid receptor antagonist인 naloxone에 의 한 반전여부를 확인하기 위해 total IgE, antigen-specific IgE, IFN-${\gamma}$ 및 IL-4 mRNA 발현량을 측정하여 다음과 같은 결과를 얻었다. 1. 전침자극은 DNP-KLH로 인해 과도하게 생산 된 혈청 total IgE 및 antigen-specific IgE를 감소시킴으로서 알러지 반응에 대한 유의한 억제능을 발휘하였으며, naloxone 투여로 전침 의 효과가 상쇠된 것으로 미루어 opioid system이 전침에 의한 항알러지 효과에 중요한 역할을 하는 것으로 추정된다. 2. 또한 전침자극은 DNP-KLH로 인한 TH2 cytokine의 편향상태에 대하여 TH1/TH2 평형조절능을 가진다는 것을 확인하였으며, naloxone으로 반전되지 않는 것으로 미루어 전침이 미치는 보조 T cell 분화에 대한 효과 는 opioid system에 의존하지 않는 것으로 추정된다.

• Molecules and Cells
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• 제41권5호
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• pp.454-464
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• 2018

Crosstalk between G-protein signaling and glutamatergic transmission within the brain reward circuits is critical for long-term emotional effects (depression and anxiety), cravings, and negative withdrawal symptoms associated with opioid addiction. A previous study showed that Regulator of G-protein signaling 4 (RGS4) may be implicated in opiate action in the nucleus accumbens (NAc). However, the mechanism of the NAc-specific RGS4 actions that induce the behavioral responses to opiates remains largely unknown. The present study used a short hairpin RNA (shRNA)-mediated knock-down of RGS4 in the NAc of the mouse brain to investigate the relationship between the activation of ionotropic glutamate receptors and RGS4 in the NAc during morphine reward. Additionally, the shRNA-mediated RGS4 knock-down was implemented in NAc/striatal primary-cultured neurons to investigate the role that striatal neurons have in the morphine-induced activation of ionotropic glutamate receptors. The results of this study show that the NAc-specific knock-down of RGS4 significantly increased the behaviors associated with morphine and did so by phosphorylation of the GluR1 (Ser831) and NR2A (Tyr1325) glutamate receptors in the NAc. Furthermore, the knock-down of RGS4 enhanced the phosphorylation of the GluR1 and NR2A glutamate receptors in the primary NAc/striatal neurons during spontaneous morphine withdrawal. These findings show a novel molecular mechanism of RGS4 in glutamatergic transmission that underlies the negative symptoms associated with morphine administration.

• The Korean Journal of Pain
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• 제26권1호
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• pp.14-20
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• 2013

Background: Nefopam, a non-opiate analgesic, has been regarded as a substance that reduces the requirement for morphine, but conflicting results have also been reported. The inhibition of monoamine reuptake is a mechanism of action for the analgesia of nefopam. The spinal cord is an important site for the action of monoamines however, the antinociceptive effect of intrathecal nefopam was not clear. This study was performed to examine the antinociceptive effect of intrathecal (i.t.) nefopam and the pattern of pharmacologic interaction with i.t. morphine in the formalin test. Methods: Male Sprague-Dawley rats were implanted with an i.t. catheter, and were randomly treated with a vehicle, nefopam, or morphine. Formalin was injected into the hind-paw 10 min. after an i.t. injection of the above experiment drugs. After obtaining antinociceptive $ED_{50}$ of nefopam and morphine, the mixture of nefopam and morphine was tested for the antinociceptive effect in the formalin test at a dose of 1/8, 1/4, 1/2 of $ED_{50}$, or $ED_{50}$ of each drug followed by an isobolographic analysis. Results: Intrathecal nefopam significantly reduced the flinching responses in both phases of the formalin test in a dose-dependent manner. Its effect, however, peaked at a dose of $30{\mu}g$ in phase 1 (39.8% of control) and $10{\mu}g$ during phase 2 (37.6% of control). The isobolograhic analysis indicated an additive interaction of nefopam and morphine during phase 2, and a synergy effect in antinociception during phase 1. Conclusions: This study demonstrated that i.t. nefopam produces an antinociceptive effect in formalin induced pain behavior during both phases of the formalin test, while interacting differently with i.t. morphine, synergistically during phase 1, and additively during phase 2.

• The Korean Journal of Pain
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• 제34권2호
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• pp.210-216
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• 2021

Background: Postherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. Despite the effectiveness of anticonvulsants, antidepressants, and lidocaine patches in reducing PHN, many patients still face intractable pain disorders. In this randomized controlled study, we evaluated whether hydromorphone through intravenous patient-controlled analgesia (IV PCA) was effective in relieving PHN. Methods: Patients with PHN were randomly divided into two groups, one group received oral pregabalin with IV normal saline, another group received oral pregabalin with additional IV PCA hydromorphone for two weeks. Efficacy was evaluated at 1, 4, and 12 weeks after the end of the treatments. Results: Two hundred and one patients were followed up for 12 weeks. After treatment, numerical rating scale (NRS) score of patients in the hydromorphone group was significantly lower than that of the control group, and the difference of NRS scores between the two groups was statistically significant at 4 and 12 weeks after treatment. The frequency of breakthrough pain in the hydromorphone group was significantly lower than that in the control group 1 and 4 weeks after treatment. After treatment, the quality of sleep in the hydromorphone group was significantly improved compared with the control group. The most common adverse reactions in the hydromorphone group were dizziness and nausea, with no significant respiratory depression. Conclusions: IV PCA hydromorphone combined with oral pregabalin provides superior pain relief in patients with PHN, which is worthy of clinical application and promotion.