• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.15 no.1
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• pp.76-95
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• 2002

Allergic rhinitis and allergic dermatitis are common allergic diseases. Galgeun-tang has been used for treating various diseases, which include allergic rhinitis and allergic dermatitis. Experimental sutdies have been done to research the anti-allergic effects of Galgeun-tang, Gamigalgeun-tang and Geomahwanggalgeun-tang. We have observed: the vascular permeability response induced by serotonin and histamine, the contact dermatitis response induced by picryl chloride, the delayed type hypersensitivity response to SRC, the mice paw edema induced by carrageenin, and the rectal temperature in febrile rats induced by endotoxin, as well as the writhing syndrome induced by $0.7{\%}$ acetic acid. The results were as follows: 1. In the vascular permeability response to intradermal serotonin and histamine, Galgeun-tang and Gamigalgeun-tang showed a significant inhibitory effect. However Geomahwanggalgeun-tang showed an insignificant inhibitory effect. 2. In the contact dermatitis response induced by picryl chloride, Galgeun-tang and Gamigalgeun-tang showed a signigicant inhibitory effect. However Geomahwanggalgeun-tang showed an insignificant inhibitory effect. 3. In the delayed type hypersensitivity response to SRC, Galgeun-tang, Gamigalgeun-tang and Geomahwanggalgeun-tang showed a significant inhibitory effect. 4. In the mice paw edema induced by carrageenin, Galgeun-tang and Gamigalgeun-tang showed a significant inhibitory effect. However Geomahwanggalgeun-tang showed an insignificant inhibitory effect. 5. In the rectal temperature in febrile rats induced by endotoxin, Galgeun-tang, Gamigalgeun-tang and Geomahwanggalgeun-tang showed a significant inhibitory effect. 6. In the writhing syndrome induced by a $0.7{\%}$ acetic acid solution. Galgeun-tang and Gamigalgeun-tang showed a significant inhibitory effect. However Geomahwanggalgeun-tang showed an insignificant inhibitory effect.

• The Korean Journal of Pain
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• v.34 no.4
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• pp.479-486
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• 2021

Background: Prior studies have reported that 40%-90% of the patients with celiac plexus-mediated visceral pain benefit from the neurolytic celiac plexus block (NCPB), but the predictive factors of response to NCPB have not been evaluated extensively. This study aimed to identify the factors associated with the immediate analgesic effectiveness of NCPB in patients with intractable upper abdominal cancer-related pain. Methods: A retrospective review was performed of 513 patients who underwent NCPB for upper abdominal cancer-related pain. Response to the procedure was defined as (1) a decrease of ≥ 50% or ≥ 4 points on the numerical rating scale (NRS) in pain intensity from the baseline without an increase in opioid requirement, or (2) a decrease of ≥ 30% or ≥ 2 points on the NRS from the baseline with simultaneously reduced opioid consumption after NCPB. Logistic regression analysis was performed to determine the factors associated with successful responses to NCPB. Results: Among the 513 patients included in the analysis, 255 (49.8%) and 258 (50.2%) patients were in the non-responder and responder group after NCPB, respectively. Multivariable logistic regression analysis showed that diabetes (odds ratio [OR] = 0.644, P = 0.035), history of upper abdominal surgery (OR = 0.691, P = 0.040), and celiac metastasis (OR = 1.496, P = 0.039) were the independent factors associated with response to NCPB. Conclusions: Celiac plexus metastases, absence of diabetes, and absence of prior upper abdominal surgery may be independently associated with better response to NCPB for upper abdominal cancer-related pain.

• 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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2000.04a
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• pp.10-14
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• 2000

The cycloooxygenase enzymes catalyze the oxidative conversion of arachidonic acid into prostag1andin H$_2$Which mediates both benificial and pathological effects. The COX-1 is constitutively expressed in most tissues and in blood platelets wherease the expression of COX-2 isoform is induced in response to inflmmatory stimuli such as cyctokynes. Thus the identification of a novel COX-2 selective inhibitor should offer excellent antiinflammatory activity with minimal side effects such as gastrointestinal toxicity. Recently, a group of structurally unique and biologically active pimarane diterpenoids has been isolated from indigenous Korean medicinal plants. These new diterpenoids turned out to be potential analgesic and antiinflammatory agent due to their potent inhibitory activities of prostaglandin synthesis. We have also found that the inhibition of PGE$_2$synthesis is attributed to the potent COX inhibition by pimarane diterpenoid in arachidonic acid cascade. In conjunction with development of new analgesic and nonsteroidal antiinflammatory agent, a series of works on these diterpenoids have been extensively carried out in our laboratories. These efforts involve the structure-activity relationship of pimaradienoic acid, molecular modelings and COX inibitory activities as well as actiinflammatory effects of its structural analogues. In addition, the total syntheses of the new natural pimarane diterpenoids, their stereoisomers and other structural variants were intensively investigated.

• Clinical and Experimental Pediatrics
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• v.63 no.1
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• pp.25-29
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• 2020

Background: Pain during the developmental period may adversely affect developing neuronal pathways and result in adverse neurodevelopmental, cognitive, and behavioral effects in later life. Immunizations, e.g., hepatitis B vaccine (HBV), administered at birth are painful experiences to which neonates are universally subjected. Purpose: Here we aimed to study and compare the effectiveness of various nonpharmacological pain management methods in newborns to enable the development of safe and effective analgesic methods for newborns. Methods: This prospective study was conducted at a tertiary care hospital in the Himalayan region. Three hundred term healthy neonates were divided into 6 groups of 50 each. Groups 1-5 were intervention groups, patients of which received a nonpharmacological intervention (breastfeeding, nonnutritive sucking, rocking, 25% sucrose, or distilled water) before the intramuscular HBV, while patients in group 6 received no intervention. The pain response in each group after the HBV injection was assessed and compared using cry duration and Douleur Aigue Nveau-ne (DAN) score, a behavioral acute pain rating scale for newborns. Results: Cry duration was decreased in all intervention groups, significantly so in the sucrose (19.90 seconds), breastfeeding (31.57 seconds), and nonnutritive sucking (36.93 seconds) groups compared with controls (52.86 seconds). DAN scores decreased significantly (P<0.05) at one or more points i.e. 30, 60, or 120 seconds in the breastfeeding and 25% sucrose intervention groups compared with controls. Conclusion: Oral sucrose and nonnutritive sucking are simple yet underutilized nonpharmacological interventions that effectively reduce pain in newborns.

• The Korean Journal of Pain
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• v.25 no.1
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• pp.1-6
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• 2012

Background: Curcumin has been reported to have anti-inflammatory, antioxidant, antiviral, antifungal, antitumor, and antinociceptive activity when administered systemically. We investigated the analgesic efficacy of intrathecal curcumin in a rat model of inflammatory pain. Methods: Male Sprague Dawley rats were prepared for intrathecal catheterization. Pain was evoked by injection of formalin solution (5%, $50{\mu}l$) into the hind paw. Curcumin doses of 62.5, 125, 250, and $500{\mu}g$were delivered through an intrathecal catheter to examine the flinching responses. The $ED_{50}$ values (half-maximal effective dose) with 95% confidence intervals of curcumin for both phases of the formalin test were calculated from the dose-response lines fitted by least-squares linear regression on a log scale. Results: In rats with intrathecal administration of curcumin, the flinching responses were significantly decreased in both phases. The slope of the regression line was significantly different from zero only in phase 2, and the $ED_{50}$ value (95% confidence interval) of curcumin was $511.4{\mu}g$ (23.5-1126.5). There was no apparent abnormal behavior following the administration of curcumin. Conclusions: Intrathecal administration of curcumin decreased inflammatory pain in rats, and further investigation to elucidate the precise mechanism of spinal action of curcumin is warranted.

• Neurospine
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• v.15 no.4
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• pp.348-352
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• 2018

Objective: Postoperative dynamic cryo-compression (DC) therapy has been proposed as a method of reducing pain and the inflammatory response in the early postoperative period after orthopedic joint reconstruction surgery. Our aim was to analyze the analgesic efficacy of DC therapy after adult lumbar spinal surgery. Methods: DC was applied for 30 minutes every 6 hours after surgery. Pain was measured by a visual analogue scale (VAS) in the preoperative period, immediately after surgery, and every 6 hours postoperatively for the first 72 hours of the hospital stay. Patients' pain medication requirements were monitored using the patient-controlled analgesia system and patient charts. Twenty patients who received DC therapy were compared to 20 historical controls who were matched for demographic and surgical variables. Results: In the postanesthesia care unit, the mean VAS back pain score was $5.87{\pm}0.9$ in the DC group and $6.95{\pm}1.0$ (p=0.001) in the control group. The corresponding mean VAS scores for the DC vs. control groups were $3.8{\pm}1.1$ vs. $5.4{\pm}0.7$ (p < 0.001) at 6 hours postoperatively, and $2.7{\pm}0.7$ vs. $6.25{\pm}0.9$ (p<0.001) at discharge, respectively. The cumulative mean analgesic consumption of paracetamol, tenoxicam, and tramadol in the DC group vs. control group was $3,733.3{\pm}562.7mg$ vs. $4,633.3{\pm}693.5mg$ (p<0.005), $53.3{\pm}19.5mg$ vs. $85.3{\pm}33.4mg$ (p<0.005), and $63.3{\pm}83.4mg$ vs. $393.3{\pm}79.9mg$ (p<0.0001), respectively. Conclusion: The results of this study demonstrated a positive association between the use of DC therapy and accelerated improvement in patients during early rehabilitation after adult spine surgery compared to patients who were treated with painkillers only.

• The Korean Journal of Pain
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• v.21 no.3
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• pp.173-178
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• 2008

Background: The intrathecal (IT) $GABA_A$ receptor antagonist, bicuculline (BIC), results in tactile allodynia (TA) through disinhibition in the spinal cord. Such disinhibition is considered to be an important mechanism for neuropathic pain. Agmatine, an endogenous polyamine, has a neuro-protective effect in the central nervous system. We investigated the analgesic effects and mechanisms of agmatine action on BIC-induced TA. Methods: Male Sprague-Dawley rats, weighting 250-300 g, were subjected to implantations of PE-10 into the lumbar subarachnoid space for IT drug injection. Five days after surgery, either $10{\mu}l$ of normal saline (NS) or agmatine ($30{\mu}g$ or $10{\mu}g$) in $10{\mu}l$ NS were injected 10 min prior to BIC ($10{\mu}g$) or NMDA ($5{\mu}g$). We assessed the degree of TA (graded 0: no response, 1: mild response, 2: moderate response, 3: strong response) every 5 min for 30 min. Areas under curves and degree of TA were expressed as mean ${\pm}$ SEM. Results were analyzed using one-way ANOVA followed by a Tukey test for multiple comparisons. P < 0.05 was considered significant. Results: IT BIC-induced strong TA reached its peak and plateaued between 10 to 15 min. IT NS-NMDA induced mild transient TA for up to 15 min. Preemptive IT AG attenuated IT BIC-induced TA dose dependently and preemptive IT AG10 completely abolished the IT NMDA-induced TA. Conclusions: Preemptive IT AG attenuated the IT BIC-induced TA through inhibitory actions on postsynaptic NMDA receptor activation. AG might be a viable therapeutic option in the treatment of neuropathic pain.

• Journal of Ginseng Research
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• v.32 no.1
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• pp.1-7
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• 2008

Ginseng saponin has been shown to inhibit the development of dependence on morphine, cocaine, methamphetamine, but the antinarcotics effects of ginseng on nalbuphine remains still largely unknown. Ginseng administration attenuated the naloxone-induced jumping behavior on nalbuphine dependent mice. The development of morphine dependence was mediated through ${\mu}-opioid$ receptor, however, development of nalbuphine dependence was mediated through ${\kappa}-opioid$ receptor. However, it was found that the efficacy of analgesic antagonism of GTS was mediated through the serotonergic mechanism, not mediated through the opioid receptor. In addition, ginseng administration modulated cellular signal transduction in the brain. The increased NMDA receptor subunit (NR1, pNR1), phosphate extracellular signal regulated protein kinase (pERK), phosphate cAMP response element binding protein (pCREB) expression by nalbuphine was decreased by the administration of ginseng powder in cortex, hippocampus, striatum of rat brain. These results suggest that ginseng could be one of the targets of antinarcotic therapies to reduce the development of tolerance and dependence on nalbuphine as well as morphine.