• The Korean Journal of Pain
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• v.14 no.2
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• pp.150-155
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• 2001

Background: Tramadol is known to be a weak opioid. However, it has also been shown that tramadol is an effective norepinephrine and serotonin uptake blocker, which may be effective in the treatment of neuropathic pain. The present study was undertaken in order to assess the antinociceptive action of tramadol and to investigate possible antinociceptive mechanisms by using antagonists in an animal neuropathic pain models in rats. Methods: Rats were prepared with tight ligation at the left 5 and 6th lumbar spinal nerves (Kim and Chung's neuropathic pain model). The antinociceptive effects of tramadol (10, 20, and 50 mg/kg i.p.) in rats with neuropathic pain were assessed. Additionally, following coadministration of antagonists such as naloxone (1 mg/kg i.p.), yohimbine (1 mg/kg i.p.) and ritanserin (1 mg/kg i.p.) with 50 mg/kg of tramadol, the responses to mechanical and thermal stimuli were measured over a two-hour period. Results: Tramadol displayed potent antinociceptive effects in a dose-dependent manner on rats with neuropathic pain (P < 0.05). The effects of tramadol were inhibited by coadministered naloxone and yohimbine in rats with mechanical and thermal allodynia, respectively (P < 0.05). However, there were no significant changes in the pain behaviors in the case of ritanserin. Conclusions: Tramadol showed significant antinociceptive effects in rats with regards to neuropathic pain against both mechanical and thermal allodynia. The antinociceptive effect on the mechanical stimuli is medicated via an opioid receptor. However, it appears that the antinociceptive effects on thermal allodynia are mediated via a noradrenalin receptor vice a serotonergic receptor.

• The Korean Journal of Pain
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• v.14 no.2
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• pp.225-230
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• 2001

Background: Opioids such as morphine are widely used in the treatment for pain, but chronic treatment with morphine can be complicated by the development of tolerance. The mechnisms of tolerance were still not completely understood, but recently it has been reported that NOS inhibitors can prevent development of morphine tolerance in animals. The present study accessed the possible role of supraspinal NO on antinociceptive effect of morphine in morphine tolerance using a highly specific inhibitor of the neuronal isoform of NOS, 1-(2-trifluoromethylphenyl) imidazole (TRIM). Methods: Thirty two male SD rats (300 g) were prepared with intracerebroventricular (icv) and IV cannulae. We administrated IV morphine, 3 mg/kg, daily for 4 days, resulting in tolerance. On the fifth day, a challenge dose of morphine, 3 mg/kg, was administered following pretreatment with icv TRIM, $10{\mu}g$. We also evaluated the antinociceptive effect of icv TRIM alone and the effect on a single dose of morphine (3 mg/kg) in morphine nave rats. Antinociception from morphine was determined by response to intraplantar injection of 5% formalin $100{\mu}l$ was qualified as the number of flinches in the first 0-10 min (first phase), 10-40 min Phase IIa, and 40-60 min (Phase IIb). Results: Pretreatment with icv TRIM significantly enhanced the antinociceptive effects of systemically administered morphine in morphine tolerant rats. The antinociceptive effect of morphine in opioid nave rats was also significantly increased by pretreatment with icv TRIM. Conclusions: Our results further support the hypothesis that supraspinal NO modulates morphine-sensitive nociceptive process in morphine tolerance due to chronic intravenous administration.

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.45-50
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• 1982

Yeum et al. formulated a new hot-plate method using the threshold temperature, and there are some controversies on the effects of naloxone and diazepam on the antinociceptive action. In this paper, the comparison of three methods registering analgesic activity and the application of the new hot-plate method formulated by Yeum et al. on the study of the influences of naloxone and diazepam on the analgesic effect of morphine were tried in male mice. The results obtained were summarized as follows; 1) The least-square regression lines of the morphine analgesia plotted against log-dose showed the correlation coefficient of above 0.90, but the competitive antagonism produced by naloxone (0.1 mg/kg) against the analgesia was more prominently demonstated by the new hot-plate method than the other methods: original hot-plate method and electrical stimulation method. 2) In the experiment using the new hot-plate method, the log dose-response curve of morphine (y=7.30 x+49.80, r=0.998) was shifted to the right by the pretreatment of naloxone (0.1 mg/kg), but was slightly shifted to the left by the pretreatment of diazepam (2.5 mg/kg). This study suggests that for the analgesia experiment, the new hot-plate method is superior to the original hot-plate method or the electrical stimulation method, and that the potentiative effect of diazepam on the morphine anagesia is not significant.

• Journal of Acupuncture Research
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• v.20 no.4
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• pp.11-23
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• 2003

Objective: In this study, the analgesic effect of gold injection aqua-acupuncture on CFA induced arthritis in rats was inverstigated. Furthermore, to determine the antinociceptive mechanism of gold injection aqua-acupuncture, naloxone and yohimbine were administrated intraperitoneally 15min prior to the gold injection aqua-acupuncture. Methods: The experimental groups were divided into 6 groups. Control group, NSI, AMI, AMI+SL : AMI+Nx, AMI+Yb. Thereafter we measured the chages of TFL between control and experimental groups. Results: 1. The tail flick latency induced by CFA was significantly increased on AMI as compared with the NSI group. 2. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of naloxone. The anti-nociceptive effect of AMI was completely antagonized by naloxone(an opioid receptor antagonist). 3. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of yohimbine. The anti-nociceptive effect of AMI was completely antagonized by yohimbine(${\alpha}2$-adrenoceptor antagonist). Conclusions: According to the results, gold injection aqua-acupuncture has significant analgesic effects on adjuvant induced arthritis in rats and the effect of anti-nociception was mediated by opiodergic system and ${\alpha}2$-adrenergic system.

• Journal of Acupuncture Research
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• v.20 no.2
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• pp.85-97
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• 2003

Introduction : In this study, the analgesic effect and its mechanism of bee venom aqua-acupuncture on complete Freund's adjuvant-induced arthritis in rats was investigated. It has been reported from a neurochemical standpoint that bee venom exerts antinociceptive effects on inflammation and that the opioid system and adrenergic system play important roles in acupuncture analgesia. however, it is not known whether central opioid and ${\alpha}2$-adrenergic components of the intrinsic descending analgesic system are activated after bee venom aqua-acupuncture. Methods : Bee venom(1mg/kg) was subcutaneously aqua-acupunctured into Joksamni($ST_{36}$) of rats with complete Freund's adjuvant(CFA)- induced arthritis and was checked of increase in TFL. Opioid and ${\alpha}_2$-adrenergic neurotransmitter system were examined by naloxone as an opioid receptor antagonist, and yohimbine as ${\alpha}_2$-adrenoceptor antagonist prior to bee venom aqua-acupuncture. Results : The following results have been obtained. 1. The tail flick latency in the rat model with adjuvant-induced arthritis was significantly decreased in 2 weeks. 2. The tail flick latency in the rat model with adjuvant-induced arthritis was increased in bee venom aqua-acupuncture group compared to the normal saline aqua-acupuncture group. 3. Analgesic effect of bee venom was antagonized by yohimbine not by naloxone pretreatment in the rat model adjuvant-induced arthritis. Conclusions : Bee venom aqua-acupuncture has an analgesic effect on the rat model of adjuvant-induced of adjuvant-induced arthritis and has antinociception mediated by ${\alpha}_2$-adrenergic system.

• Physical Therapy Korea
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• v.5 no.2
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• pp.15-22
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• 1998

Laser photobiostimulation (LPBS) is one of the recent additions to therapeutic procedures used in chronic pain management. Though widely used, a clear understanding of its mechanism of action was not disclosed. In addition, the energy density that produces maximal benefit has not yet been established. The purposes of this study were to determine the effects of LPBS on pain relief in rat and to determine treatment dosage. Eight, 8-week old female, Sprague-Dawley rats were employed. All subjects were assigned to one of four groups: a sham laser group, a 0.4 $J/cm^2$ laser group, a 2.0 $J/cm^2$ laser group, and a 6.0 $J/cm^2$ laser group. Ga-As laser (904 nm wavelength) of three different energy densities (0.4, 2.0, 6.0 $J/cm^2$) was applied on a tail acupuncture point and tail-flick latencies were measured five times pre-and post-treatment as following schedules: 30 minutes, 1 hour. 24 hours. 48 hours, and 7 days later. An increase in pain threshold was demonstrated following LPBS, employing rat tail-flick test. LPBS of 2.0 $J/cm^2$ produced hypoalgesia of rapid onset and short duration (1 hour, 24 hours) while the response to 6.0 $J/cm^2$ was delayed and lasted longer (48 hours, 7 days). LPBS of 0.4 $J/cm^2$ did not produce any hypoalgesia.

• The Journal of Internal Korean Medicine
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• v.19 no.2
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• pp.88-106
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• 1998

This study was designed to elucidate the antiinflammatory, cardiovascular, antithrombotic, and analgesic effect of Sambitang. The antiinflammatory effects was measured by the method of carrageenin induced edema, protein leakage test using CMC-pouch, and the effect of Sambitang on the cardiovascular system was observed by the change of flow rate of Ringer solution in the vascular system in the ear of rabbit, and the contraction and dilatation of rat tail artery. Death rate, platelet aggregation, plasma coagulation activity was observed for the measurement of the anticoagurative effect of Sambitang, and the analgesic effect was measured by the acetic acid method and hot plate method. The result was as follows: 1. Sambitang administration, edema and protein leakage was significantly decreased. 2. The drug increased the auricular blood flow in rabbit. 3. The drug relaxed the artery contraction by pretreated norepinephrine in rat. 4. The drug inhibited the death rate of mouse which was led to thromboembo- lism by serotonin and collagen. 5. The drug inhibited the platelet aggregation in rat. 6. The drug prolonged the prothrombin time and activated partial thromboplastin time on the test of plasma coagulation factor activity in rat, but was not valuable. 7. The slight anagesic effect of Sambitang extract was confirmed by the observation of writhing syndrome, paw licking time, and escape time.

• YAKHAK HOEJI
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• v.49 no.5
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• pp.370-374
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• 2005

Lactoferrin is a multifunctional protein that is found in milk, neutrophils, and other biological fluids, and its receptors have also been identified in the central nervous system. Recently, it was reported that bovine milk-derived lacto­ferrin (BLF) produced analgesia via a $\mu$-opioid receptor-mediated response in the spinal cord. However the precise mech­anism of this analgesic effect is remains unclear. In Randall-Selitto paw pressure study, each single administration of morphine (10 mg/kg) and BLF (50, 100 and 200 mg/kg) induced analgesia, however, NMDA receptor antagonist MK-801 (0.1, 0.2 and 0.3 mg/kg), inhibited analgesia induced by BLF (100 mg/kg). Intracerebroventricular infusion (I.C.V.) of N­methyl-D-aspartic acid (NMDA) ($0.3\;{\mu}g/8.0\;{\mu}l/hr/day$), as a NMDA receptor agonist, reversed inhibition of MK-801 (0.3 mg/kg) on analgesia induced by BLF (100 mg/kg). These results suggest that BLF have analgesic effect, through NMDA recep­tor activation.

• Journal of Trauma and Injury
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• v.20 no.2
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• pp.115-118
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• 2007

Purpose: A eutectic mixture of local anesthetics (EMLA$^{(R)}$) cream has been used as a topical anesthetic to reduce the pain of procedures penetrating the skin. It is generally applied for 40 to 60 minutes before the painful procedure. Because of the long application period, EMLA$^{(R)}$ is not useful in the emergency department (ED). The purpose of this study was to determine whether a 20-minute application of 9.6% lidocaine would be useful in reducing the pain of routine peripheral intravenous cannulation in the ED. Methods: We examined 27 male and 19 female patients ages over 18 years of age who required intravenous cannula insertion. Intravenous insertion was performed on 46 patients: 24 patients in the placebo group (mean age: 40.0 years) and 22 in the 9.6% lidocaine group (mean age: 37.6 years). The 9.6% lidocaine or placebo gel was applied and covered with an occlusive dressing for 20 minutes. Pain was scored by the patients using a 0- to 10-cm visual analogue scale. Results: The patients in the 9.6% lidocaine group (mean pain score: 3.4) experienced less pain than those in the placebo group (mean: 5.3), and the difference was statistically significant (p=0.029). Conclusion: We concluded that a 20-minute application of 9.6% lidocaine is safe and effective for reducing pain associated with venipuncture.

• Advances in pediatric surgery
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• v.20 no.1
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• pp.7-11
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• 2014

The present study compared the postoperative analgesic effects of ilioinguinal and iliohypogastric nerve block with infiltration of local anesthetics (bupivacaine) into the wound in children after inguinal hernia repair. Ninety children below 7 years old who were scheduled elective inguinal hernia repair were randomly allocated into one of three groups. The patients in nerve block (NB) group, ilioinguinal and iliohypogastric nerve block was done with 0.5 mL/kg of 0.25% bupivacaine. The patients in infiltration of local anesthetics (LI) group, 0.5 mL/kg of 0.25% bupivacaine was infiltrated into the wound after surgery. The patients in control group were allocated as a Control group. Postoperative pain was assessed at 1, 3, 5, and 24 hours after operation with FLACC scale and additional analgesic consumption were counted. The three groups were not significantly different in age, sex, body weight, and duration of operation. Pain scores at 1 hour and 3 hours after operation were significantly higher in Control group than in NB group and LI group (p<0.01), whereas there were no difference between NB group and LI group. The rescue analgesics administration was significantly higher in Control group (n=11) than in NB group (n=6) and LI group (n=7) (p<0.05). There were 2 cases of transient femoral nerve palsy in NB group. Both of ilioinguinal and iliohypogastric nerve block and infiltration of local anesthetics into the wound provided effective postoperative analgesia in early postoperative period following inguinal hernia repair in children. But no difference between the two methods. Technically, infiltration of local anesthetics into the wound was easier and safer than ilioinguinal and iliohypogastric nerve block.