• The Korean Journal of Pain
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• 제9권2호
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• pp.318-325
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• 1996

Background: Sympathectomy relieves pain in sympathectically maintained pain, and subcutaneous injection of norepinephrine(NE) can rekindle mechanical allodynia. However, the mechanism of rekindling is not clear. The purpose of this study is to investigate which subtype of $\alpha$-adrenoceptor is involved in NE-induced rekindling of mechanical allodynia in sympathectomized neuropathic rats. Methods: Neuropathic injury was produced by tightly ligating the left L5 and L6 spinal nerves of 36 male Sprague-Dawley rats and bilateral lumbar sympathectomy was done at two weeks postoperatively. Starting at 7 days after sympathectomy, rekindling of mechanical allodynia was induced by NE and clonidine injected into the left paw, which was reversed by pretreatment of phentolamine and idazoxan. Mechanical allocynia was quantified by measuring the frequency of foot lifts to two von Frey filaments applied to the paw. Results: All tested rats displayed well-developed signs of mechanical allodynia at the left paw that were abolished by a bilateral lumbar sympathectomy. Subcutaneous (s.c.) injection of NE (0.05 ${\mu}g$) into the affected paw of sympathectomized neuropathic rats rekindled previous mechanical allodynia. These effects could be mimicked by an ${\alpha}_2$-receptor agonist clonidine, but not by an ${\alpha}_1$-receptor agonist phenylephrine. The NE-induced rekindling of mechanical allodynia was significantly reduced by prior s.c. injection of a mixed $\alpha$-receptor antagonist phentolamine (20${\mu}g$) and ${\alpha}_2$-receptor antagonist idazoxan(20${\mu}g$), but not by a ${\alpha}_1$-receptor antagonist terazosin (20${\mu}g$). The pretreatment of idazoxan produced dose-related inhibition of NE-induced rekindling of mechanical allodynia. The rekindling induced by ${\alpha}_2$-receptor agonist clonidine (5${\mu}g$) was also reversed by prior s.c. injection of ${\alpha}_2$-receptor antagonist idazoxan (20${\mu}g$). Conclusion: Subcutaneous injection of NE into the paw of sympathectomized neuropathic rats rekindles mechanical allodynia, which is reversed by an ${\alpha}_2$-, but not by an ${\alpha}_1$-receptor antagonist. Therefore, rekindling of mechanical allodynia in sympathectomized neuropathic rats is mediated by ${\alpha}_2$-adrenoceptor.

• 한방안이비인후피부과학회지
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• 제18권1호
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• pp.50-60
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• 2005

Objective : We have studied to know effects of Ligigeopoongsan(LGS, 理氣祛風散) on mechanical allodynia, cold allodynia and c-Fos protein expression in the model of neuropathic pain of rats. Methods : The model of neuropathic pain was made by injured tibial nerve and sural never while common peroneal never was maintained. After 2weeks, we performed behavioral test for 7 days to try out mechanical allodynia using von frey filament and cold allodynia using acetone, which are calculated by counting withdrawal response on foot. Rat brains removed and sliced on 8th days. Serial sections were immunohistochemically reacted with polyclonal c-Fos antibody. The numbers of c-Fos protein immunoreactive neurons in the central gray were examined using scion image program. Results : 1. Mechanical allodynia in LGS-2, LGS-3 groups were significantly diminished compared with the control group. 2. Cold allodynia in LGS-3 group was significantly diminished compared with the control group. 3. c-Fos protein expression on the central gray LGS-2, LGS-3 groups were significantly lower than that of control group. conclusions : We have noticed that LGS(理氣祛風散) diminished mechanical and cold allodynia in the model of neuropathic pain compared with the control group. c-Fos protein expression in the central gray of that group was also decreased compared with the control group. Pain control group were LGS was accumulated time goes by. This study can be used as a basic resource on a study and a treatment of pain.

• Journal of Acupuncture Research
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• 제18권6호
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• pp.215-224
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• 2001

Objcetive : Neuropathic pain sometimes arises from a partial peripheral nerve injury. This kind of pain is usually accompanied by spontaneous burning pain, allodynia and hyperalgesia. It has been well known that acupuncture is effective to the pain control from ancient time in Asia. However, it is not clear whether acupuncture can control neuropathic pain. The aim of the present study is to examine if acupuncture stimulation may be effective to the mechanical allodynia in a rat model of neuropathic pain. Methods : To produce neuropathic pain, under sodium pentobarbital anesthesia, the right superior caudal trunk was resected between the S3 and S4 spinal nerves. After the neuropathic surgery, we examined if the animals exhibited the behavioral signs of mechanical allodynia. The mechanical allodynia was assessed by stimulating the tail with von Frey hair (bending force : 2.0g). three or 6 weeks after the neuropathic surgery, acupuncture stimulation was delivered to Houxi (SI 3) as the following parameters (2HZ frequency, 0.07mA intensity and 3msec duration) for 30 minutes. Results : The stimulation of Houxi (SI 3) acupoint relieved the behavioral signs of mechanical allodynia. Conclusion : Our results suggest that acupuncture can control the mechanical allodynia of neuropathic pain.

• The Korean Journal of Pain
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• 제21권2호
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• pp.106-111
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• 2008

Background: Chronic pain after thoracotomy has been recently reproduced in a rat model that allows investigating the effect of potentially beneficial drugs that might reduce the incidence of allodynia or alleviate pain. Local anesthetics produce antinociception in normal animals and alleviate mechanical allodynia in animals with nerve injury although their mechanisms of action may differ in these situations. Our purpose of this study was to test whether the preoperative intercostal nerve block of bupivacaine could prevent the development of allodynia in a rat model of chronic postthoracotomy pain. Methods: All male Sprague-Dawley rats were anesthetized and the right 4th and 5th ribs were exposed surgically. The pleura were opened between the ribs to which a retractor was placed and was opened 10 mm in width. Retraction was maintained for one hour. Total 1 mg of 0.5% bupivacaine was injected at the intercostal nerves before (n = 17) or after (n = 16) surgery. A control group (n = 25) that underwent rib retraction did not receive any drug. Rats were tested for mechanical allodynia using calibrated von Frey filaments applied around the incision site during the three weeks following surgery. Results: The incidence of development of mechanical allodynia in the group that received intercostal injection with bupivacaine before surgery was significantly lower than that in the control group (P < 0.05). Conclusions: Preoperative intercostal nerves block around the surgical incision before thoracotomy may decrease the incidence of postthoracotomy pain syndrome.

• The Korean Journal of Pain
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• 제12권1호
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• pp.8-15
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• 1999

Following peripheral nerve injury, rats will show a tactile allodynia and hyperalgesia. But the mechanism of allodynia is still obscure. The present studies, using rats rendered allodynia by loosely constrictive ligation of the common sciatic nerve (Bennett Model) and tight ligation of L5 & L6 spinal nerve (Chung Model), aimed to investigate the changes of metabotrophic glutamate receptor type 5 on the development of tactile allodynia. Male Sprague-Dawley rats (130~200 g) were anesthetized with halothane, the rats were randomly divided into one of these three groups, Group 1 (Sham operation), Group 2 (Bennett model) and Group 3 (Chung model). Seven days after surgical procedure, the animal was reanesthetized and decapitated. The spinal cord was quickly removed and stored at deep freezer for polymerase chain reaction (RT-PCR). In Group 2&3, rats showed that tactile allodynia checked by up-down method with calibrated 8 von Frey hair. The level of gene expression of mGluR5 mRNA was significantly increased in group 2 and 3. These increases was significantly different from sham operation, group 1. It was also showed that the increasing patterns of group 2 and 3 in the gene expression were similar correlation with the results of the threshold for tactile allodynia on von Frey hair test. Even though there were some differences between Bennett model and Chung model, these results suggested that mGluR5 had partly attributed to making a tactile allodynia from these models.

• The Korean Journal of Pain
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• 제36권1호
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• pp.51-59
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• 2023

Background: This study investigated the effect of an excess and a deficit of spinal 5-hydroxytryptamine (5-HT) on the mechanical allodynia and neuroglia activation in a rodent pain model of carrageenan inflammation. Methods: Male Sprague-Dawley rats were implanted with an intrathecal (i.t.) catheter to administer the drug. To induce an excess or deficit of 5-HT in the spinal cord, animals were given either three i.t. 5-HT injections at 24-hour intervals or a single i.t. injection of 5,7-dihydroxytryptamine (5,7-DHT) before carrageenan inflammation. Mechanical allodynia was measured using the von Frey test for 0-4 hours (early phase) and 24-28 hours (late phase) after carrageenan injection. The changes in the activation of microglia and astrocyte were examined using immunofluorescence of the dorsal horn of the lumbar spinal cord. Results: Both an excess and a deficit of spinal 5-HT had no or a minimal effect on the intensity of mechanical allodynia during the early phase but prevented the attenuation of mechanical allodynia during the late phase, which was observed in animals not treated with i.t. 5-HT or 5,7-DHT. Animals with an excess or deficit of 5-HT showed stronger activation of microglia, but not astrocyte, during the early and late phases, than did normal animals. Conclusions: Imbalance in the descending 5-HT pathway in the spinal cord could aggravate the mechanical allodynia and enhance the activation of microglia, suggesting that the spinal 5-HT pathway plays an essential role in maintaining the nociceptive processing in balance between facilitation and inhibition in inflammatory pain caused by carrageenan inflammation.

• Biomolecules & Therapeutics
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• 제25권3호
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• pp.259-265
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• 2017

This study aimed to investigate the analgesic effect of substance P (SP) in an animal model of neuropathic pain. An experimental model of neuropathic pain, the chronic constriction injury (CCI) model, was established using ICR mice. An intravenous (i.v.) injection of SP (1 nmole/kg) was administered to the mice to examine the analgesic effects of systemic SP on neuropathic pain. Behavioral testing and immunostaining was performed following treatment of the CCI model with SP. SP attenuated mechanical allodynia in a time-dependent manner, beginning at 1 h following administration, peaking at 1 day post-injection, and decaying by 3 days post-injection. The second injection of SP also increased the threshold of mechanical allodynia, with the effects peaking on day 1 and decaying by day 3. A reduction in phospho-ERK and glial fibrillary acidic protein (GFAP) accompanied the attenuation of mechanical allodynia. We have shown for the first time that i.v. administration of substance P attenuated mechanical allodynia in the maintenance phase of neuropathic pain using von Frey's test, and simultaneously reduced levels of phospho-ERK and GFAP, which are representative biochemical markers of neuropathic pain. Importantly, glial cells in the dorsal horn of the spinal cord (L4-L5) of SP-treated CCI mice, expressed the anti-inflammatory cytokine, IL-10, which was not seen in vehicle saline-treated mice. Thus, i.v. administration of substance P may be beneficial for improving the treatment of patients with neuropathic pain, since it decreases the activity of nociceptive factors and increases the expression of anti-nociceptive factors.

• The Korean Journal of Pain
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• 제8권1호
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• pp.18-24
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• 1995

We produced the causalgiform pain by the tight ligation of L5 and L6 spinal nerves in the adult rats. To evalute the effect of Ketamine -noncompetitive NMDA (N-methyl-D aspartate) antagoinst- on the causalgiform pain, we tested the changes of; withdrawal sensitivity to the innocuous mechanical stimulation of Von Frey hair 2.35 g(mechanical allodynia); withdrawal frequency to the cold stimulation of acetone (cold allodynia); and total withdrawal time (second) to the cold ($4^{\circ}C$) plate stimulation (cold hyperalgesia) after the administration of 1 mg, 3 mg, 10 mg/kg ketamine. The results were as follows: 1) Cold hyperalgesia was significantly reduced (p<0.05) by 1 mg, 3mg, 01 mg/kg ketamine. 2) Cold allodynia and mechanical allodynia was significantly reduced (p<0.05) by 10 mg/kg ketamine. Above results suggest a therapeutic utility of ketamine in treatment of causalgia - especially, cold hyperalgesia.

• Journal of Acupuncture Research
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• 제21권3호
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• pp.145-167
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• 2004

Objective : Neuropathic pain can be caused by a partial peripheral nerve injury. This kind of pain is usually accompanied by spontaneous burning pain, allodynia and hyperalgesia. It is not clear that scolopendrid aqua-acupuncture can control neuropathic pain effectively. The purpose of this study is to examine if scolopendrid aqua-acupuncture may be effective to the neuropathic pain (mechanical allodynia, cold allodynia) in a rat model of neuropathic pain. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, tibial nerve and sural nerve was resected. After the neuropathic surgery, the author examined if the animals exhibited the behavioral signs of allodynia. The allodynia was assessed by stimulating the medial malleolus with von Frey filament and acetone. Three weeks after the neuropathic surgery, scolopendrid aqua-acupuncture was injected at Hwando(GB30) one time a day for one week. After that the author examined the withdrawl response of neuropathic rats' legs by von Frey filament and acetone stimulation. And also the author examined c-fos in the midbrain central gray of neuropathic rats and the change of WBC count in the blood of neuropathic rats. Results & Conclusion : 1. The scolopendrid aqua-acupuncture injected at Hwando(GB30) decreased the withdrawl response of mechanical allodynia in SHA-1, SHA-2 and SAH-3 group as compared with control group. 2. The scolopendrid aqua-acupuncture injected at Hwando(GB30) decreased the withdrawl response of chemical allodynia(cold allodynia) in SHA-1, SHA-2 and SAH-3 group as compared with control group. 3. The scolopendrid aqua-acupuncture injected at Hwando(GB30) showed the significant difference between sham group and control group(p=0.01), sham and SHA-3 group(p=0.026), control group and SHA-1 group(p=0.01), control group and SHA-2 group(p=0.024) in the c-fos expression. 4. The scolopendrid aqua-acupuncture injected at Hwando(GB30) showed the significant difference between sham group and SHA-3 group(p=0.010), control group and SHA-3 group(p=0.006) in the WBC count.

• Journal of Acupuncture Research
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• 제26권6호
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• pp.67-76
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• 2009

Objectives : The purpose of this study is to examine if Radix Aconiti herbal acupuncture may be effective to the neuropathic pain(mechanical allodynia, cold allodynia) in a rat model of neuropathic pain. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, L5 spinal nerve was ligated by 6-0 silk thread. After neurophathic surgery, the author examined if the animals exhibited the behavioral sign of allodynia. The allodynia was assessed by stimulating the medial malleolus with von frey filament and acetone. Three days after the neuropathic surgery, Radix Aconiti herbal acupuncture was injected at Hwando($GB_{30}$) one time per two days for 2 weeks. After that, the author examined the withdrawal response of neuropathic rats' legs by von frey filament and acetone stimulation. And also the author examined c-Fos in the midbrain central gray of neuropathic rats and the change of WBC, RBC, HGB, HCT count in the blood of neuropathic rats. Results : The Radix Aconiti herbal acupuncture injected Hwando($GB_{30}$) decreased the withdrawal response of mechanical allodynia that assessed with von frey filament in RA1-$GB_{30}$, RA2-$GB_{30}$ group as compared with control group. The Radix Aconiti herbal acupuncture injected Hwando($GB_{30}$) decreased the withdrawal response of chemical allodynia(cold allodynia) that assessed with acetone in RA1-$GB_{30}$, RA2-$GB_{30}$ group as compared with control group. The Radix Aconiti herbal acupuncture injected Hwando($GB_{30}$) showed the significant between control group and RA2-$GB_{30}$ group in the c-Fos expression. The Radix Aconiti herbal acupuncture injected Hwando($GB_{30}$) did not show the significant between control group and RA1-$GB_{30}$ group, RA2-$GB_{30}$ group and RA3-$GB_{30}$ group in the WBC, RBC, HGB, HCT count. Conclusions : We have noticed that Radix Aconiti herbal acupuncture at Hwando($GB_{30}$) decreased mechanical allodynia and cold allodynia in the model of neuropathic pain compared with the control group. C-fos expression in the central gray of that group was also decreased compared with the control group. This study can be used as a basic resource on a study and a treatment of pain.