• The Korean Journal of Pain
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• v.12 no.1
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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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• v.9 no.2
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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.

• Journal of Korean Neurosurgical Society
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• v.50 no.2
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• pp.109-113
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• 2011

Objective : Peripheral neuropathy is characterized by hyperalgesia, spontaneous burning pain, and allodynia. The purpose of this study was to investigate the effect of rolipram, a phosphodiesterase-4-specific inhibitor, in a segmental spinal nerve ligation model in rats. Methods : Both the L5 and L6 spinal nerves of the left side of the rats were ligated. Phosphodiesterase-4 inhibitor (rolipram) and saline (vehicle) were administered intraperitoneally. We measured mechanical allodynia using von Frey filaments and a nerve conduction study. Results : The mechanical allodynia, which began to manifest on the first day, peaked within 2 days. Multiple intraperitoneal injections of rolipram ameliorated the mechanical allodynia. Furthermore, an intraperitoneal administration of rolipram improved the development of pain behavior and nerve conduction velocity. Conclusion : This study suggests that the phosphodiesterase-4 inhibitor, rolipram, alleviates mechanical allodynia induced by segmental spinal nerve ligation in rats. This finding may have clinical implications.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.18 no.1
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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.

• International Journal of Oral Biology
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• v.35 no.3
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• pp.75-81
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• 2010

The present study investigated the role of ERK in the onset of mechanical and cold allodynia in a rat model of compression of the trigeminal ganglion by examining changes in the air-puff thresholds and number of scratches following the intracisternal injection of PD98059, a MEK inhibitor. Male Sprague Dawley rats weighing between 250 and 260 g were used. Under anesthesia, the rats were mounted onto a stereotaxic frame and received 4% agar ($10\;{\mu}l$) solution to compress the trigeminal ganglion. In the control group, the animals were given a sham operation without the application of agar. Changes in behavior were examined at 3 days before and at 3, 7, 10, 14, 17, 21, 24, 30, and 40 days after surgery. Compression of the trigeminal ganglion significantly decreased the air-puff thresholds. Mechanical allodynia was established within 3 days and persisted over postoperative day 24. To evaluate cold allodynia, nociceptive scratching behavior was monitored after acetone application on the vibrissa pad of the rats. Compression of the trigeminal ganglion was found to produce significant cold allodynia, which persisted for more than 40 days after surgery. On postoperative day 14, the intracisternal administration of $1\;{\mu}g$ or $10\;{\mu}g$ of PD98059 in the rat model significantly decreased the air-puff thresholds on both the ipsilateral and contralateral side. The intracisternal administration of $10\;{\mu}g$ of PD98059 also significantly alleviated the cold allodynia, compared with the vehicle-treated group. These results suggest that central ERK plays an important role in the development of mechanical and cold allodynia in rats with compression of the trigeminal ganglion and that a targeted blockade of this pathway is a potential future treatment strategy for trigeminal neuralgia-like nociception.

• Journal of Acupuncture Research
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• v.20 no.1
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• pp.177-190
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• 2003

Objective : This study was intended to investigate the analgesic effects of electroacupuncture(EA) on mechanical allodynia according to the frequency and intensity of EA. Also to know if mechanical allodynia and the analgesic effects of EA is related to the sympathetci nervous system and/or the purinergic system. Methods : mechanical allodynia-induced rats were produced by resecting S1-S2 nerve. The zusanli(ST36) was used for acupoint and the rats were divided into 4 groups. Each group was given different stimuli[low frequency low intensity-EA(LFLI-EA), low frequency high intensity-EA(LFHI-EA), high frequency low intensity-EA(LFHI-EA), high frequency high intensity-EA(HFHI-EA)]. Futhermore, to make sympathectomy6-OHDA and phentolamine were administered intraperitonially and the concentration of norepinephrine(NE) were measured. As a ATP blocker, suramin was applied for this study. Results : Comparing to control group, each of the 4 groups(LFLI-EA, LFHI-EA, HFLI-EA, HFHI-EA) showed a significant reduction of response frequency of mechanical allodynia. LFHI-EA was more effective than that of LFLI-EA. The LFHI-EA group also had longer lasting effects from the stimulation than the other groups. Sympathectomy didn't show any reduction of response frequency of mechanical allodynia.(Each n=6, n=4). Nor did both sympathectomy and ATP block. The response frequency wasn't reduced by sympathectomy or by sympathectomy and ATP block, but was significantly reduced with LFHI-EA Conclusions : These results suggest that EA has a significant analgesic effect on mechanical allodynia which has no connection with NE and/or ATP.

• Journal of Acupuncture Research
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• v.26 no.6
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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.

• The Korean Journal of Pain
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• v.9 no.2
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• pp.311-317
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• 1996

Background: Following peripheral nerve injury, rats will show a tactile allodynia and hyperalgesia. But the mechanism of allodynia is still obscure. Previous studies have shown this allodynia was reversed by intrathecal alpha-2 agonists and NMDA antagonists, but not by morphine. In formalin test, either the pretreatment of NMDA antagonist or morphine prevents the hyperalgesia. The present studies, using rats rendered allodynic by ligation of the left L5 and L6 nerves, aimed to investigate the effects of pretreatment of MK-801 and morphine on the development of tactile allodynia. Methods and Material: Male Sprague-Dawley rats (100~150g) were anesthetized with halothane, the left L5 and L6 spinal nerves were ligated tightly by 6-0 black silk. For sham operation muscle dissection was performed but the spinal nerve was not ligated. For pretreatment of drugs, MK-801 (NMDA antagonist; 0.3 mg/kg). CNQX (non-NMDA) antagonist; 0.3 mg/kg), morphine (1 mg/kg) or saline (placebo) was administered subcutaneously 30 minutes before operation. A second dose was administered subcutaneously 24 hours after operation and further doses were given daily for 2 days further. The volume of injection was 5 ml/kg. To assess the mechanical allodynia, paw withdrawal thresholds of ipsilateral limb were determined using 8 von Frey hairs. Results: Within 2 days saline, CNQX or morphine injected rats developed tactile allodynia (paw withdrawal threshold was about 2g), and persisted for over 2 weeks. Pretreatment of MK-801 delayed the development of tactile allodynia for 3 days comparing to that of saline injected rat. Conclusion: NMDA receptor in the central nerve system plays an important role in the development of tactile allodynia induced by peripheral nerve injury. But the mechanism may be different from hyperalgesia developed in formalin test.

• Journal of Acupuncture Research
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• v.21 no.1
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• pp.240-251
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• 2004

Objective: We have studied to know effects of acupuncture at SI3, BL40, SI3 BL40 on mechnical allodynia, cold allodynia and c-fos protein expression in a model of neuropathic pain of rat. Methods: A model of neuropathic pain was made by injuring tibial nerve and sural nerve while common peroneal nerve was maintained. after 2 weeks, we performed behavioral tests for 7 days to try out mechnical 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: Mechanical allodynia in the SI3, BL40, SI3 BL40 groups were diminished compared with the control group. Cold allodynia in the SI3, BL40, SI3 BL40 groups were diminished compared with the control group. c-Fos protein expression on the central gray in the SI3 group were lower than that of the control group. Conclusions: We have noticed that acupuncture at SI3, BL40, SI3 BL40 diminished mechanical allodynia and cold allodynia in a 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 using acupunture was accumulated as 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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• v.18 no.6
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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.