• The Journal of Korean Medicine
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• v.25 no.4
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• pp.8-14
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• 2004

Objective : Achyranthes japonica Nakai (AJ) has been classified as a herb that activates blood flow and clears the stagnated blood. In this study, we evaluated its anti-nociceptive and anti-inflammatory activity in animals to clarify the effect of AJ on pain or inflammation. Methods : ICR mice and Sprague-Dawley rats were pretreated with an ethanolic extract of AJ with two dosages of 200 mg/kg (p.o.) and 400 mg/kg (p.o.). Nociceptive responses of acute pain were determined by hotplate and tail-flick tests. The effects of AJ on inflammation were evaluated by flexion/extention test and mechanical hyperalgesia test in models induced by both carrageenan and Complete Freund's Adjuvant (CFA). Results : AJ showed significant analgesic effects in both hotplate and tail-flick tests at the dose of 400 mg/kg. It also produced a significant inhibition of carrageenan-induced paw edema and CFA induced arthritis in rats at the dose of 400 mg/kg. Conclusion : We have demonstrated the analgesic and anti-inflammatory properties of an 80% ethanolic extract of AJ in animals. This suggests the application of AJ in relief of pain or inflammatory disease.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.6
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• pp.505-510
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• 2013

Electroacupuncture (EA) is a modified form of acupuncture that utilizes electrical stimulation. We previously showed that EA stimulated rats were divided into responders that were sensitive to EA and non-responders that were insensitive to EA based on the tail flick latency (TFL) test. The dopamine beta-hydroxylase (DBH) gene was more abundantly expressed in the hypothalamus of responder rats than non-responder rats. To determine whether overexpression of DBH gene expression in the hypothalamus modulate EA analgesia, we constructed a DBH encoding adenovirus and which was then injected into the hypothalamus of SD rats. Microinjection of DBH or control GFP virus into the hypothalamus had no changes on the basal pain threshold measured by a TFL test without EA treatment. However, the analgesic effect of EA was significantly enhanced from seven days after microinjection of the DBH virus, but not after injection of the control GFP virus. DBH expression was significantly higher in the hypothalamus of DBH virus injected rat than control GFP virus or PBS injected rats. Moreover, expression of the DBH gene did not affect the body core temperature, body weight, motor function or learning and memory ability. Although the functional role of DBH in the hypothalamus in the analgesic effect of EA remains unclear, our findings suggest that expression of the DBH gene in the hypothalamus promotes EA analgesia without obvious side-effects.

• The Korean Journal of Pain
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• v.12 no.2
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• pp.211-216
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• 1999

Background: Transdermal fentanyl patch (TDFP) is a simple, noninvasive analgesic with continuous effect. The aim of this study was to evaluate the postoperative analgesic effect of TDFP. Methods: Sixty healthy patients undergoing cesarean section were divided into 3 groups. Postoperative pain was controlled with different methods; Group I: application of TDFP-$25{\mu}g/hr$, Group II: intramuscular injection of ketoprofen; Group III: continuous epidural block. Pain scores (numerical rating scale, NRS), number of patients who needed additive ketoprofen injections and side effects were recorded at 8, 20, 32, 44 hours postoperatively. Results: There was no significanant difference in pain score between Group I and Group II. The numbers of patients who need additive ketoprofen injections were lower in group I than group II. Pruritis (25%), nausea/vomiting (10%), leg numbness (40%) was experienced in group III, but not in Group I & II. Conclusions: TDFP-$25{\mu}g/hr$ for postoperative pain control is simpler and more convinient than intramuscular injection of analgesics.

• The Korean Journal of Pain
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• v.13 no.1
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• pp.38-43
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• 2000

Background: Preemptive analgesia may decrease postoperative pain by preventing nociceptive inputs generated during surgery. The preemptive effect of intravenous nalbuphine was examined in gynecological surgery. Methods: Forty female patients scheduled for gynecological surgery were randomly allocated into two groups. Each patient received 10 mg of intravenous nalbuphine as a bolus dose at the closure of peritoneum in group I (n=20) and before the skin incision in group II (n=20). After the bolus dose, the intravenous patient controlled analgesia (IV-PCA) which contained 50 mg of nalbuphine, 120 mg of ketorolac, 0.25 mg of droperidol and 90 ml of 5% dextrose water was given continuously at the rate of 2 ml/min. The postoperative visual analogue scale pain score (VAS), the total amount of the analgesics used, the degree of satisfaction of the patients and the developement of side effects were examined for 2 days. Results: VAS were significantly lower in group II than in group I after 9 and 12 hours. The cumulative consumption of analgesics in group II was significantly less than in group I. Most patients were satisfied with this regimen. There were no remarkable side effects. Conclusions: Preemptive analgesia with intravenous nalbuphine decreased postoperative pain and analgesic requirement. The analgesic effect of IV-PCA with nalbuphine-ketorolac was effective in control of postoperative pain in gynecologic surgery.

• Korean Journal of Oriental Medicine
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• v.12 no.3 s.18
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• pp.49-58
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• 2006

Although the usage of acupuncture for pain has increased in recent years, the mechanisms of acupuncture analgesia (AA) remain unclear. The lack of suitable experimental animal models for persistent pain, which show clear AA, has been the major stumbling block in the investigation of the physiological mechanisms of AA. In the present study, we test AA in two knee arthritis models induced by injection of CFA or carrageenan as persistent pain models. After induction of arthritis, the rat subsequently showed a reduced stepping force of the affected limb for the next several days. Electroacupuncture (EA) was applied to an acupuncture point each on the contralateral forelimb for 30 minutes under gaseous anesthesia. After the termination of EA, behavioral tests measuring stepping force were periodically conducted during the next several hours. EA produced a significant improvement of stepping force of the foot lasting for at least 2 hours when applied to LR2 in CFA model, and applied to ST36 in carrageenan model, but both points did not produce any significant effects in each other model. Further experiments showed that intraperitoneal pretreatment of naltrexone, a non-selective opioid antagonist, did not reduced the EA-induced improvement of stepping force in both of two models. These data suggest that EA produce analgesic effect in knee arthritic pain and the analgesic effect is specific to the acupuncture point depending on painful conditions.

• The Korean Journal of Pain
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• v.11 no.2
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• pp.235-240
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• 1998

Background: Preoperative blocking of surgical nociceptive inputs may prevent sensitization of CNS and reduce postoperative pain. The stress responses to surgical trauma consist of increase in catabolic hormones and decrease in anabolic hormones. We studied whether preoperative intravenous morphine could affect postoperative pain and change plasma cortisol and serum glucose levels. Methods: Thirty eight patients undergoing total abdominal hysterectomy were randomly assigned to one of three groups. Control group (n=11) did not received intravenous morphine, preoperative group (n=13) received intravenous morphine (0.1 mg/kg as a bolus 10 min before operation and followed by 1.5 mg/hr for 10 hours), postoperative group (n=14) received the same doses and method of intravenous morphine of preoperative group postoperatively. Postoperative pain relief was provided with i.v. fentanyl through Patient-Controlled-Analgesia Pump. Postoperative visual analogue scores (VAS), analgesic requirement (first request time, total amounts used), side effects, plasma cortisol and serum glucose levels were compared. Results: VAS were different between control group and the other two goups, but were not different between preoperative and postoperative group. Total amounts of used fentanyl were not different among groups, but first request time were significantly delayed in the preoperative group compared with the other two groups ($66.2{\pm}33.9$ vs $39.0{\pm}15.4$ and $45.0{\pm}14.9$ min respectively, p<0.05). Plasma cortisol and serum glucose levels were not different among groups. Conclusions: Above dosage of preoperative and postoperative morphine has analgesic effect, but could not block surgical stress induced plasma cortisol and serum glucose increase.

• The Korean Journal of Pain
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• v.24 no.3
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• pp.131-136
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• 2011

Background: Pregabalin is an anticonvulsant and analgesic agent that interacts selectively with the voltage-sensitive-$Ca^{2+}$-channel alpha-2-delta subunit. The aim of this study was to evaluate whether the analgesic action of intrathecal (IT) pregabalin is associated with KATP channels in the rat formalin test. Methods: IT PE-10 catheters were implanted in male Sprague-Dawley rats (250.300 g) under inhalation anesthesia using enflurane. Nociceptive behavior was defined as the number of hind paw flinches during 60 min after formalin injection. Ten min before formalin injection, IT drug treatments were divided into 3 groups: normal saline (NS) $20\;{\mu}l$ (CON group); pregabalin 0.3, 1, 3 and $10\;{\mu}g$ in NS $10\;{\mu}l$ (PGB group); glibenclamide $100\;{\mu}g$ in DMSO $5\;{\mu}l$ with pregabalin 0.3, 1, 3 and $10\;{\mu}g$ in NS $5\;{\mu}l$ (GBC group). All the drugs were flushed with NS $10\;{\mu}l$. Immunohistochemistry for the $K_{ATP}$ channel was done with a different set of rats divided into naive, NS and PGB groups. Results: IT pregabalin dose-dependently decreased the flinching number only in phase 2 of formalin test. The log dose response curve of the GBC group shifted to the right with respect to that of the PGB group. Immunohistochemistry for the $K_{ATP}$ channel expression on the spinal cord dorsal horn showed no difference among the groups 1 hr after the formalin test. Conclusions: The antinociceptive effect of pregabalin in the rat formalin test was associated with the activation of the $K_{ATP}$ channel. However, pregabalin did not induce $K_{ATP}$ channel expression in the spinal cord dorsal horn.

• 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.

• YAKHAK HOEJI
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• v.45 no.1
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• pp.116-124
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• 2001

Nitric oxide is a labile, gaseous, broad spectrum second messenger that used in various tissues and cells. If it is induced by endogenously and exogenously in the neuronal cells, it is able to mediate analgesia or hyperalgesia at the periphery and in the spinal level respectively. This dual role of nitric oxide in the sensory system is very intriguing but has not been fully understood yet. In this experiment, acetylcholine (300 $\mu$g/paw), sodium nitroprusside (600 $\mu$g/paw), and L-arginine (300 $\mu$g/paw) represented antinociceptive effect to noxious topical stimulus, but pronociceptive responses followed by spinally application (20$\mu$g/5$\mu$l, 10$\mu$g/3$\mu$l, 500$\mu$g/5$\mu$l respectively). Calcium ion is critical element which activates nitric oxide synthase, therefore verapamil (300 $\mu$g/paw) and NOS inhibitor (20 mg/kg, L-NAME or L-NOArg) are injected into right hind paw (i.pl.). When verapamil is combined with NOS inhibitors analgesic effects through NO-cGMP pathway are inhibited as compared with ACh alone. Diluted formalin (2.5%), when injected into rats'hind paw (0.05 ml), elicited a biphasic algesic responses and nitric oxide had an analgesic effect on both $A\delta$ and C sensory nerve fibers which manipulate the phases respective1y. Nitric oxides, which produced from constitutive nitric oxide synthase, activated cyclooxygenase-type I and then prostaglandins are produced from them. So, indomethacin and ibuprofen, inhibitors of COX$_1$enzyme, when pretreated intraperitoneally (100 mg/kg) could reduce the hyperalgesic state. From these results, it is possible to imagine that the intrathecally administered NO donors expressed hyperalgesia through both long-term potentiation mechanism and arachidonic acid-prostaglandin cascade.

• Korean Journal of Veterinary Research
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• v.45 no.2
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• pp.263-271
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• 2005

To compare the sedative effects using intermittent intravenous bolus injection with tiletamine-zolazepam (n = 5, TZ group), xylazine-ketamine (n = 5, XK group) and propofol (n = 5, PI group), we investigated the changes of hemodynamic (heart rate, arterial pressure), $SpO_2$, rectal temperature, respiratory rate and pain score during 60 minute sedation and 40 minute recovery period in beagle dogs. The value of rectal temperature was significantly higher in PI groups (p<0.05) during recovery period. The value of heart rate was significantly lower in XK group (p<0.05) during sedation. The changes of respiratory rate were similar tendency in all groups. The change of $SpO_2$ was stable during sedation and value was significantly higher in PI group (p<0.05) during recovery period. The value of systolic arterial pressure (SAP) was significantly lower in XK group (p<0.05) than PI group during sedation and recovery period. Low analgesic effect occurred in PI group. We concluded that intravenous anesthesia by intermittent bolus injection with propofol is useful in stabilizing rectal temperature, $SpO_2$ and hemodynamic during sedation and provide fast recovery, but have low analgesic effect.