• Journal of Acupuncture Research
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• v.33 no.2
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• pp.97-108
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• 2016

Objectives : This study was performed to investigate the analgesic effect of Styrax japonica pharmacopuncture on formalin induced pain in rats and to figure out efficient extraction method. Methods : The subjects were divided into 5 groups ; normal group(treated with normal saline at KI03, and injected normal saline at right hindpaw after 35 minutes), control group(treated with normal saline at KI03, and injected with formalin at right hindpaw after 35 minutes), water group(treated by hot water extraction pharmacopuncture at KI03, and injected with formalin at right hindpaw after 35 minutes), ethanol group(treated with ethanol extraction pharmacopuncture at KI03, and injected with formalin at right hindpaw after 35 minutes), and ultrasound group(treated with ultrasound extraction pharmacacupuncture and injected with fromalin formalin at right hindpaw after 35 minutes). We conducted a formalin test with ultrasonic vocalization( USV), and after the test checked for substance P, Aspartate aminotransferase(AST), and Alanine aminotransferase(ALT) concentration in the blood for each of the groups. Results : There was a significant analgesic effect of Styrax japonica pharmacopuncture in the early phase of the formalin test, and pharmacopuncture made with an ultrasound extracting method was observed to have a better analgesic effect than other extracting methods in early phases. The substance P concentration decreased significantly in the Styrax japonica pharmacopuncture treated group and no difference was found in the AST and ALT concentration of each group. Conclusion : These results demonstrated that Styrax japonica pharmacopuncture had analgesic effects in noxious nociceptors stimulation. Also pharmacopuncture made with an ultrasound extracting method had a better analgesic effect than others.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.6
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• pp.299-306
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• 2008

Sometimes, spinal cord injury (SCI) results in various chronic neuropathic pain syndromes that occur diffusely below the level of the injury. It has been reported that behavioral signs of neuropathic pain are expressed in the animal models of contusive SCI. However, the observation period is relatively short considering the natural course of pain in human SCI patients. Therefore, this study was undertaken to examine the time course of mechanical and cold allodynia in the hindpaw after a spinal cord contusion in rats for a long period of time (30 weeks). The hindpaw withdrawal threshold to mechanical stimulation was applied to the plantar surface of the hindpaw, and the withdrawal frequency to the application of acetone was measured before and after a spinal contusion. The spinal cord contusion was produced by dropping a 10 g weight from a 6.25 and 12.5 mm height using a NYU impactor. After the injury, rats showed a decreased withdrawal threshold to von Frey stimulation, indicating the development of mechanical allodynia which persisted for 30 weeks. The withdrawal threshold between the two experimental groups was similar. The response frequencies to acetone increased after the SCI, but they were developed slowly. Cold allodynia persisted for 30 weeks in 12.5 mm group. The sham animals did not show any significant behavioral changes. These results provide behavioral evidence to indicate that the below-level pain was well developed and maintained in the contusion model for a long time, suggesting a model suitable for pain research, especially in the late stage of SCI or for long term effects of analgesic intervention.

• Journal of Acupuncture Research
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• v.33 no.1
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• pp.37-46
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• 2016

Objectives : The objective of this study is to evaluate the analgesic effects of Drosera rotundifolia L. pharmacopuncture on formalin-induced pain in Sprague-Dawley(SD) rats. Methods : In this experiment there were four groups, each with six SD rats. In the normal group (NOR), normal saline $40{\mu}L$ was injected at right KI3, and normal saline $40{\mu}L$ was injected at right hindpaw 35 minutes later. In the control group (CON), normal saline $40{\mu}L$ was injected at right KI3, and formalin 5 % $40{\mu}L$ was injected at right hindpaw 35 minutes later. In the Drosera rotundifolia L. pharmacopuncture 3 % group (DP3), Drosera rotundifolia L. pharmacopuncture 3 % $40{\mu}L$ was injected at right KI3, and formalin 5 % $40{\mu}L$ was injected at right hindpaw 35 minutes later. In the Drosera rotundifolia L. pharmacopuncture 5 % group (DP5), Drosera rotundifolia L. pharmacopuncture 5 % $40{\mu}L$ was injected at right KI3, and formalin 5 % $40{\mu}L$ was injected at right hindpaw 35 minutes later. We analyzed ultrasonic vocalization (USV), Substance P, aspartate aminotransferase(AST), and alanine aminotransferase(ALT). Results : In the early phase of USV, both DP3 and DP5 had an analgesic effect. In the late phase, DP5 had an analgesic effect compared to CON. Substance P in DP5 was significantly decreased compared to CON. In regards to blood AST and ALT, there was no significant difference among NOR, CON, DP3 or DP5. Conclusion : These results suggest that Drosera rotundifolia L. pharmacopuncture helps to reduce formalin-induced pain. It's mechanism is related to substance P, and Drosera rotundifolia L. pharmacopuncture has no influence on liver toxicity.

• Applied Microscopy
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• v.36 no.4
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• pp.271-277
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• 2006

Mast cells (MCs) are granulated cells that play a pivotal role in allergic reaction and inflammation. The granules of mast cells are known to be rich in zinc (Zn). Male Sprague-Dawley rats were used. We injected $200{\mu}L$ of complete Freund's adjuvant (CFA) subcutaneously in the dorsal aspect of one hindpaw Finally, zinc selenium autometallography(AMG) was done by Danscher's method. The present study showed the ultrastructures of zinc-containing mast cells found in inflammatory area following an complete freund's adjuvant (CFA) inoculation into the rat hindpaw. At light microscopic level, mast cells were round or oval, at average $12{\mu}m$ in diameter, with many filopodia extending from the cell surface. Because the rather small and spherical nucleus was centrally placed; it was frequently obscured by the cytoplasmic granules, it sometimes could not be seen. Mast cells were distributed chiefly in the vicinity of small blood vessels. In most preparation many mast cells were ruptured and their granules escaped into the surrounding tissue. In electron micrographs, The secretory granules were at average $0.5{\mu}m$ in diameter and were limited by a membrane. The cell surface contained numerous microvilli and folds. Their interior was heterogenous in appearance. The nucleus was surrounded by large numbers of prominent vesicels and a well developed Golgi apparatus, but scant endoplasmic reticulum.

• Journal of Veterinary Clinics
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• v.16 no.1
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• pp.155-162
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• 1999

This study was performed to assess that clinco-therapeutic effect of natural Italian honeybee (Apis mellifera) venom in adjuvant-induced arthritic rat. Ninety Sprague- Dawley rats of male were injected with complete Freund's adjuvant (CFA). Adjuvant arthritis was produced by a single subcutaneous injection of 1 mg Mycobacterium butyricum suspended in 0.1 ml paraffin oil into the right hindpaw. Righting reflex was uniformly lost and considered to be the point of arthritis development on day 14 after CFA injection. Experimental groups were divided into three groups. When arthritis was developed in the rat hind-paw, tested groups were administrated with prednisolone (10 mg/kg, p.o) and honeybee venom (one bee, s.c) at an interval of two days. Control group was subcutaneously injected with 0.1 ml of physiological saline solution in the rat at an interval of two days. Clinical findings, hematological values and histopathological findings were observed during or after the drugs administration. In tested groups, the development of inflammatory edema and polyarthritis on day 14 after treatment was suppressed. No significant differences of hindpaw edema volume and lameness score between prednisolone and honeybee venom groups were observed during or after therapeutic drugs treatment. WBC counts of prednisolone and honeybee venom treatment groups as compared with the control group were getting remarkably decreased during or after the therapeutic drugs administration(p＜0.01). Erosions of articular cartilage and inflammatory cell infiltrations during or after the therapeutic drugs treatment was effectively suppressed in natural honey venom.

• The Journal of Korean Physical Therapy
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• v.22 no.3
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• pp.79-85
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• 2010

Purpose: Many trials for new therapeutic approaches such as stem cell-based transplantation have been conducted to improve the repair and regeneration of injured cord tissue and to restore functions following spinal cord injury (SCI) in animals and humans. Adipose tissue-derived stromal cells (ATSCs) have multi-lineage potential to differentiate into cells with neuron-like morphology. Most studies of stem cell transplantation therapy after SCI are focused on cellular regeneration and restoration of motor function, but not on unwanted effects after transplantation such as neuropathic pain. This study was focused on whether transplantation of ATSCs could facilitate or attenuate hindpaw pain responses to heat, cold and mechanical stimulation, as well as on improvement of locomotor function in a rat with SCI. Methods: A spinal cord injury rat model was produced using an NYU impactor by dropping a 10 g rod from a height of 25 mm on to the T9 segment. Human ATSCs (hATSCs; approximately $5{\times}10^5$ cells) or DMEM were injected into the perilesional area 9 days after the SCI. After transplantation, hindpaw withdrawal responses to heat, cold and mechanical allodynia were measured over 7 weeks. Motor recovery on the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and on the inclined plane test were also evaluated. Results: The present study demonstrated that increased hindpaw withdrawal responses to cold allodynia was observed in both groups after transplantation, but the development of cold-induced allodynia in the hATSC transplantation group was significantly larger than in the control group. The difference between the two groups in locomotor functional improvement after SCI was also significant. Conclusion: Careful consideration not only of optimal functional benefits but also of unintended side effects such as neuropathic pain is necessary before stem cell transplantation therapy after SCI.

• The Korean Journal of Pain
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• v.12 no.1
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• pp.1-7
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• 1999

Background: To study the role of spinal alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in pain behaviors caused by mild burn, we examined the effect of intrathecal administered ACEA 2085, which has been recently characterized as a high potency competitive AMPA receptor antagonist, on the thermal hyperalgesia state induced by mild burn. Methods: A thermal injury was induced by applying the left hind paw to a thermal surface ($52.5^{\circ}C$) for 45 sec. Thermal escape latency of the hind paw was determined using an underglass thermal stimulus. Thirty min after thermal injury, the paw withdrawal latency (PWL) in injured paw of all groups fell from 10~12 sec to 5~7 sec. At that time, ACEA 2085 (0.01~0.1 mcg) and 6-cyano-7-nitroquinoxalinedione (CNQX, 1~30 mcg) were injected through intrathecal heters in rats with mild burn injury on the right hindpaw. And then, PWL were measured in the both hindpaw every 30 minutes for about three hours. Results: The intrathecal injection of ACEA 2085 produced a dose dependent reversal of the hyperalgesia in the right hindpaw and more potent than CNQX, but had no effect upon the response latency of the normal left hind paw even at the largest doses. All effects were observed at doses that had no significant effect upon motor function. Conclusions: Intrathecal ACEA 2085, highly selective AMPA receptor antagonist produce a dose- dependent reversal of the thermal hyperalgesia evoked mild burn injury. These results suggested that spinal AMPA receptor play an important role in the hyperalgesia induced by mild burn injury.

• The Korean Journal of Pain
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• v.21 no.1
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• pp.18-26
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• 2008

Background: Because genetic manipulation is commonly accomplished in mice, mouse models for pain have advanced our understanding of the mechanisms of persistent pain. The purpose of this experimental study is to develop a mouse model for understanding incision induced postoperative pain. Methods: A longitudinal incision was made at the hindpaw of male DBA/2 mice. The withdrawal frequency(WF) from applications of von Frey filaments and the response frequency (RF) to blunt mechanical stimulation were examined in an incision group and a control grouP. The withdrawal latency (WL) to radiant heat and a pain score based on weight bearing were also measured. Tests were performed 1 day before incision, and 2 hours, 1-3 days, 5 days and 7 days after incision. Results: The WF for the strongest filament was $35.0{\pm}9.1%$ before incision and this increased to $100.0{\pm}0%$ at 2 hours and to $65.0{\pm}9.1%$ at 7 days after incision. The RF to the blunt stimulus was $4.1{\pm}4.1%$ before incision and $100.0{\pm}0.0%$ at 2 hours and $42.8{\pm}10.8%$ at 7 days after incision. The WL was $6.6{\pm}0.5sec$ before incision and $2.4{\pm}0.3sec$ at 2 hours and $5.9{\pm}0.6sec$ at 7 days after incision. The pain score increased from $1.1{\pm}0.8$ to $7.4{\pm}1.5$ at 2 days after incision. Conclusions: A mouse model of acute postoperative pain was developing by making a surgical incision in the mouse hindpaw. Mechanical hyperalgesia and allodynia lasting for several days demonstrate that this model has similarities to the human post-operative pain state. Future studies will allow us to further investigate the genetic and molecular mechanisms of incisional pain.

• International Journal of Oral Biology
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• v.33 no.3
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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.

• Journal of Acupuncture Research
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• v.34 no.2
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• pp.61-74
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• 2017

Objectives : This study was carried out to evaluate analgesic effects of Zanthoxylum bungeanum Maxim (ZM) pharmacopuncture on formalin-induced pains in Sprague-Dawley (SD) rats and ICR-mice. Methods : The subjects were divided 8 weeks aged rats with constant pain sensitivity into five groups; normal (treated with normal saline at Taegye (KI3) and before injected with normal saline at hindpaw), Con-1 (treated with normal saline at KI3 before injected with formalin at hindpaw), Lido-1 (treated with lidocaine at KI3), ZMWG-1 (treated with Hot water extraction pharmacopuncture of Zanthoxylum bungeanum Maxim at KI3), ZMEG-1 (treated with ethanol extraction pharmacopuncture of Zanthoxylum bungeanum Maxim at KI3). After 35 minutes, we measured ultrasonic vocalization (USV) and enzyme activities of both Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) in rat serum. In addition, Tail flick test is performed by injecting ICR mice at 5 weeks of age. And it classified into 4 groups (Con-2, Lido-2, ZMWG-2, ZMEG-2) according to the kind of drug (normal saline, lidocaine, ZMW, ZME). After each drug injection, we examined the reaction by placing the tail in water at $50^{\circ}C$. Results : ZME had analgesic effects in the early and late phase of USV during the formalin test. There were no significant differences between ZMEG-1 and Lido-1 in early and late phase of USV. Also, No significant differences observed in serum AST and ALT activity in ZMWG-1 and ZMEG-1 compared with Con-1. For tail-flick test, analgesic effect on warmth significantly increased in Lido-2 and ZMEG-2 compare to that of Con-2. Conclusion : ZME pharmacopuncture had analgesic effects on formalin-induced pain without liver toxicity. Also, tail-flick test suggest that ZME pharmacopuncture could be useful technique on analgesic effect on warmth and treatment of pains.