• The Korean Journal of Pain
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• 제19권1호
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• pp.17-21
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• 2006

Background: Cyclic guanosine monophosphate (cGMP) plays an important role in the modulation of nociception. Although local sildenafil produces antinociception, by increasing cGMP through the inhibition of phosphodiesterase 5, the effect of spinal sildenafil has not been determined. The authors evaluated the effects of intrathecal sildenafil on the nociceptive behavior evoked by formalin injection and thermal stimulation. Methods: Lumbar intrathecal catheters were implanted into rats, with formalin and Hot-Box tests used as nociceptive models. The formalin-induced nociceptive behavior (flinching response) and withdrawal latency to radiant heat were measured, and the general behaviors also observed. Results: The intrathecal administration of sildenafil produced dose-dependent suppression of the flinches in both phases in the formalin test, and increased the withdrawal latency in the Hot-Box test. No abnormal behaviors were noted. Conclusions: Sildenafil, an inhibitor of phosphodiesterase 5, is active against the nociceptive state evoked in the spinal cord by formalin and thermal stimulations. Accordingly, spinal sildenafil may be useful in the management of pain.

• The Korean Journal of Pain
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• 제14권2호
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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 Physiology and Pharmacology
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• 제1권2호
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• pp.143-149
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• 1997

We studied the effects of ginseng protopanaxadiol (PD) and protopanaxatriol (PT) saponins on the analgesia using several pain tests such as writhing, formalin, and tail-flick test. Using mouse, pretreatment of PD or PT saponins (i.p.) induced inhibition of abdominal constrictions caused by 0.9% acetic acid administration(i.p.). The $AD_{50}$ was around 27 (17-43) mg/kg for PD and 13.5 (3-61) mg/kg for PT saponins in writhing test. Both PD and PT saponins also showed the inhibition of bitings and lickings of hindpaw after administration of 1% formalin. In particular, both PD and PT saponins showed analgesic effects on second phase of pain. The $AD_{50}$ was 44.5 (26-76) mg/kg for PD and 105 (55-200) mg/kg for PT saponins in second phase of formalin test. For first phase pain inhibition by PD or PT saponins, they were required higher concentrations. However, PD saponins showed weak analgesic effects in tail-flick test with high concentration. In conclusion, we found that both PD and PT saponins have the analgesic effects in writhing test and second phase of pain in formalin test. These results suggest that both PD and PT saponins inhibit neurogenic or tonic pain rather than acute pain.

• The Korean Journal of Physiology and Pharmacology
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• 제17권5호
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• pp.417-422
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• 2013

The aim of this study was to evaluate the synergistic potentiation effect of ineffective doses of dexmedetomidine on antinociception induced by morphine and fentanyl in acute pain model in rats. Seventy albino Wistar rats were separated into 7 groups. Data for the control and sham groups were recorded. The ineffective dose of dexmedetomidine was investigated and found to be 3 ${\mu}g/kg$. Each group was administered the following medications: 3 mg/kg morphine (intraperitoneal) to Group 3, 5 ${\mu}g/kg$ fentanyl (intraperitoneal) to Group 4, dexmedetomidine 3 ${\mu}g/kg$ (subcutaneously) to Group 5, dexmedetomidine 3 ${\mu}g/kg$ (subcutaneous)+3 mg/kg morphine (intraperitoneal) to Group 6 and finally 3 ${\mu}g/kg$ dexmedetomidine (subcutaneous)+5 ${\mu}g/kg$ fentanyl (intraperitoneal) to Group 7. Just before the application and 15, 30, 60, 90 and 120 min after the administration of medication, two measurements of tail flick (TF) and hot plate (HP) tests were performed. The averages of the measurements were recorded. TF and HP latencies were the main outcomes. The analgesic effect of the combinations with dexmedetomidine+morphine (Group 6) and dexmedetomidine+fentanyl (Group 7), compared to the analgesic effect of morphine alone and fentanyl alone was significantly higher at 15, 30, 60 and 90 minutes after administration. In this study, dexmedetomidine in ineffective doses, when combined with morphine and fentanyl, potentiates the effects of both morphine and fentanyl.

• The Korean Journal of Physiology and Pharmacology
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• 제16권2호
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• pp.119-123
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• 2012

In the present study, the antinociceptive profiles of $Agrimonia$ $pilosa$ $Ledeb$ extract were examined in ICR mice. $Agrimonia$ $pilosa$ $Ledeb$ extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, $Agrimonia$ $pilosa$ $Ledeb$ extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 ${\mu}g$) was diminished by $Agrimonia$ $pilosa$ $Ledeb$ extract. Intraperitoneal (i.p.) pretreatment with yohimbine (${\alpha}_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by $Agrimonia$ $pilosa$ $Ledeb$ extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by $Agrimonia$ $pilosa$ $Ledeb$ extract in the writhing test. Our results suggest that $Agrimonia$ $pilosa$ $Ledeb$ extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of $Agrimonia$ $pilosa$ $Ledeb$ extract may be mediated by ${\alpha}_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• International Journal of Oral Biology
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• 제33권3호
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• pp.97-103
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• 2008

The present study investigated the role of peripheral group I, II, and III metabotropic glutamate receptors (mGluRs) in mustard oil (MO)-induced nociceptive response in the masseter muscles of lightly anesthetized rats. Experiments were carried out on male Sprague-Dawley rats weighing 300-350 gm. After initial anesthesia with sodium pentobarbital (40 mg/kg, i.p.), one femoral vein was cannulated and connected to an infusion pump for intravenous infusion of sodium pentobarbital. The rate of infusion was adjusted to provide a constant level of anesthesia. MO (30 ${\mu}L$) was injected into the mid-region of the left masseter muscle via a 30-gauge needle over 10 seconds. After 30 mL injection of 5, 10, 15, or 20% MO into the masseter muscle, total number of hindpaw-shaking behavior was monitored. Intramuscular administration of MO significantly produced hindpawshaking behavior in a dose-dependent manner, as compared with the vehicle (mineral oil)-treated group. Intramuscular pretreatment with 10 or 100 ng DHPG, a group I mGluRs agonist, enhanced MO-induced hindpaw-shaking behavior, while APDC (20 or 200 ${\mu}g$), a group II mGluRs agonist, or L-AP4 (2 ${\mu}g$), a group III mGluRs agonist, significantly reduced MO-induced nociceptive behavior. The antinociception, produced by group II or III mGluRs agonists, was abolished by pretreatment with LY341495, a group II mGluRs antagonist, or CPPG, a group III mGluRs antagonist, res-pectively. Based on these observations, peripheral mGluRs differentially modulated MO-induced nociceptive behavior response in the craniofacial muscle pain and peripheral group II and III mGluRs agonists could be used in treatment of craniofacial muscle nociception.

• The Korean Journal of Physiology and Pharmacology
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• 제14권5호
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• pp.285-289
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• 2010

In the present study, the antinociceptive profiles of $Campanula$ $punctata$ extract were examined in ICR mice. The $Campanula$ $punctata$ contain a large dose of saponin. $Campanula$ $punctata$ extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, $Campanula$ $punctata$ extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P ($0.7{\mu}g$) was diminished by $Campanula$ $punctata$ extract. Intraperitoneal (i.p.) pretreatment with yohimbine (${\alpha}_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by $Campanula$ $punctata$ extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by $Campanula$ $punctata$ extract in the writhing test. Our results suggest that $Campanula$ $punctata$ extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of $Campanula$ $punctata$ extract may be mediated by ${\alpha}_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• Korean Journal of Acupuncture
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• 제25권3호
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• pp.81-96
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• 2008

Objectives : The purpose of the present study is to determine the effective analgesic parameters of manual acupuncture (MA) and/or electroacupuncture (EA), thus how MA & EA of specific acupoint works after acute ankle sprain in rats. Thus, one series of experiments was designed to analyze the analgesic effects of acupuncture in either the normal or sprained rat, by comparing the behavioral features before and after MA or EA at several acupoints. Methods : Ankle sprain was induced manually by hyper-extension of ligaments of the right ankle in rat. Either MA or EA was applied to the LI4, TE17, 足三里 and SI-6 acupoints at an intensity of 2 mA (1 ms pulse duration) with a frequency of 10 Hz for 30 minutes. Results : Behaviorally, manual acupuncture or electroacupuncture produced potent analgesic effects on acute ankle sprained animals as measured by weight bearing capacity of the affected limb. Furthermore, antinociceptive effect of EA was suppressed by alpha adrenoceptor antagonist phentolamine (5 mg/kg, i.p.) but not by opioid antagonist naltrexone (10 mg/kg, i.p.). Conclusions : It is suggested that acupuncture-induced antinociception may involve the descending inhibition of ${\alpha}2$-adrenoceptor.

• Korean Journal of Acupuncture
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• 제26권2호
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• pp.75-89
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• 2009

Objectives: Warm needling combines simultaneously the effects of acupuncture and moxibustion. This study was to investigate whether warm needling could relieve acute knee arthritis induced by carrageenan in rats. Methods: To illuminate the underlying mechanisms of the warm needling-induced antinociception, weight bearing force (WBF) was observed on the acute knee arthritic rat model. Under general anesthesia, ST36, SP9, Hakjung extra point, LI4 were punctured and stimulated with 30 mg moxa ball combustion on top of the needle (${\emptyset}0.18{\times}8mm$). Results: In behavioral test, rats subsequently showed a reduced stepping force of the affected limb 3 hours after the induction of arthritis. Warm needling on the contralateral or ipsilateral ST36 failed to show antinociceptive effect on the acute knee arthritis. Warm needling on the contralateral SP9 or LI4 increased WBF values to normal level in the acute stage of the arthritis. Warm needling on the Hakjung extra-point resulted in the significant antinociceptive effects through acute stage. These effects of warm needling were suppressed by opioids receptor antagonist naltrexone (10 mg/kg, i.p.) and alpha adrenoceptor antagonist phentolamine (5 mg/kg, i.p.). Conclusion: The data suggest that warm needling-induced antinociception is differently mediated by acupoints and accomplished by activating the descending inhibitory systems including endogenous opioids and $\alpha$-adrenoceptors.

• Biomolecules & Therapeutics
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• 제5권2호
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• pp.211-214
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• 1997

In the present study, we investigated the mechanisms of antinociceptive effect and thermoregulatory action of capsaicin in guinea pigs. The administration of capsaicin (5 mg/kg, s.c.) caused a significant decrease in frequency of eye wiping, an indicative of nociceptive threshold. This antinociceptive effect of calsaicin was abolished by co-administration of capsazepine (30 mg/kg, s.c.) with capsaicin, suggesting the involvement of a vanilloid receptor in the antinociceptive action of capsaicin. The administration of capsaicin (1 mg/kg, s.c.) produced a significant decrease in body temperature of guinea pigs. The maximum decrease in body temperature by 2 degrees was shown 1 hour after the treatment, and this decrease was not reversed by coadministration of capsazepine. In conclusion, it is suggested that the mechanism of action of capsaicin-induced thermoregulation involves different pathways from that of capsaicin-induced antinociception.