• 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.

• Korean Journal of Acupuncture
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• v.28 no.2
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• pp.37-47
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• 2011

Objectives : We have studied the effects of GaAlAs (808 nm) low level laser therapy (LLLT) and acupuncture at BL40 on neuropathic pain in rats induced by lumbar spinal nerve 5 ligation. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, the lumbar spinal nerve 5 was ligated by 6-0 silk thread. After neuropathic surgery, we 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 weeks after the neuropathic surgery, GaAlAs (808 nm) low level laser and acupuncture was inserted at BL40 once a day for 6 days. We examined the withdrawal response of neuropathic rats' legs by von Frey filament and acetone stimulation. And also the author examined c-Fos, nociceptin and nociceptin receptor in the midbrain central gray of neuropathic rats. Results : The GaAlAs (808 nm) low level laser therapy and acupuncture at BL40 decreased the withdrawal response of mechanical allodynia that assessed with von Frey filament in LLLT group on 5 and 6 times and with acetone in AT group and LLLT on 6times. The LLLT and acupuncture at BL40 decreased the c-Fos protein expression in AT and LLLT groups. The 808 nm LLLT and acupuncture at BL40 decreased the nociceptin protein and nociceptin receptor protein in LLLT group. Conclusions : We have noticed that GaAlAs (808 nm) LLLT and acupuncture at BL40 decreased mechanical allodynia in the model of neuropathic pain. c-Fos, nociceptin and nociceptin receptor expression in the central gray of that group was also decreased. This study can be used as a basic resource on a study and a treatment of pain.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.2
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• pp.159-170
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• 2011

Objectives : We have studied to know analgesic effects of the combination of Aconitum Cilliare Tuber with honey in the models of peripheral neuropathic pain. Methods : Neuropathic pain model was made by ligating left 5th lumbar spinal nerve. After 3 days, combination of Aconitum Ciliare Tuber and honey extract was administrated each alternate day. Administration was divided three groups, that is NP-OA1(0.06 mg/ml), NP-OA2(0.24 mg/ml), and NO-OA3(0.96 mg/ml). After that, we examined the withdrawl response of neuropathic rats legs by von Frey filament and acetone stimulation. And also we examined c-Fos, glutamic oxaloacetic transaminase(GOT), glutamate-pyruvate transaminase(GPT) and change of weight. Results : Mechanical allodynia in NP-OA1 groups were significantly decreased compared with the control group. Cold allodynia in all experimental groups were no significant differences with the control group. c-Fos protein expression on the central grey, all experimental groups were lower than that of control groups. But, there were no statistically significant differences. Change of weight in all experimental groups were significantly increased compare with the control group. In blood serum GOT in NP-OA1, NP-OA2 groups were significantly decreased compare with the control group. In blood serum GPT in all experimental groups were no significant difference with the control group. Conclusions : We had noticed that the combination of Aconitum Ciliare Tuber and honey decreased mechanical allodynia in the model of neuropathic pain compared with the control group and it has not efficacy in elevation of GOT, GPT and weight loss etc., the element of which becomes damage to liver. This study can be proposed that Aconitum Ciliare with Honey may be applicable to neuropathic pain in clinic. But it is reliability not that cold allodynia and c-Fos expression have effectively to control pain. Therefore we have to follow up about that.

• Journal of Acupuncture Research
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• v.30 no.4
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• pp.69-78
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• 2013

Objectives : The purpose of this study is to examine whether Eucommiae Cortex pharmacopuncture may affect to the neuropathic pain in a rat model. Methods : To produce the model of neuropathic pain, under isoflurane 2.5 % anesthesia, underwent tight ligation by 6.0 silk thread and transection of the tibial and sural nerves, leaving the common peroneal nerve intact. After neuropathic surgery, the author examined if the exhibited the behavioral sign of allodynia. The allodynia was assessed by stimulating the plantar with Dynamic Plantar Aesthesiometer. Three days after the neuropathic surgery, Eucommiae Cortex pharmacopuncture was injected at Sinsu($BL_{23}$) once every week for 6 weeks. After that, the author examined the withdrawal response of neuropathic rats' leg by Dynamic Plantar Aesthesiometer. And also the author examined Bax, Bcl-2, Bax/Bcl-2 ratio in the spinal cord of neuropathic rats and the change of WBC, RBC, HGB, HCT count in the blood of neuropathic rats. Results : 1. The Eucommiae Cortex pharmacopuncture decreased the withdrawal response of mechanical allodynia that assessed with Dynamic Plantar Aesthesiometer in EC2-$BL_{23}$ group as compared with control group. 2. The Eucommiae Cortex pharmacopuncture decreased Bax/Bcl-2 ratio in EC1-$BL_{23}$, EC2-$BL_{23}$ group. But The Eucommiae Cortex pharmacopuncture injected at Sinsu($BL_{23}$) didn't change Bax, Bcl-2 expression level in the all group. 3. The Eucommiae Cortex pharmacopuncture decreased WBC count in EC1-$BL_{23}$, EC2-$BL_{23}$ group. Conclusions : We have noticed that Eucommiae Cortex pharmacopuncture decreased mechanical allodynia in the model of neuropathic pain compared with the control group. Bax/Bcl-2 ratio in spinal cord 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 neuropathic pain.

• Journal of Korean Neurosurgical Society
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• v.59 no.2
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• pp.98-105
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• 2016

Objective : Lumbar disc herniation can induce sciatica by mechanical compression and/or chemical irritation. The aim of this study was to compare the effects of GCSB-5 (Shinbaro$^{(R)}$) and NSAIDs on pain-related behavior and on the expressions of microglia, astrocytes, CGRP, TRPV1, IL-6, and CX3CL1 in a rat model of lumbar disc herniation. Methods : 112 male Sprague-Dawley rats underwent implantation of nucleus pulposus to a dorsal root ganglion (DRG). Rats were divided into five groups as follows; a saline group (the vehicle control group) (n=27), a 10 mg/kg aceclofenac group (the aceclofenac group) (n=22), and 100, 300 or 600 mg/kg GCSB-5 groups (the GCSB-5 100, 300, or 600 groups) (n=21 for each group). Rats were tested for mechanical allodynia at 3 days after surgery and at 1 day, 3 days, 7 days, 14 days, 21 days, 28 days, 35 days, 42 days, 49 days, and 56 days after treatment commencement. Immunohistochemical staining of microglia (Iba1), astrocytes (GFAP), CGRP, and TRPV1, and PCR for IL-6 and CX3CL1 were performed on spinal dorsal horns and DRGs at 56 days after medication commencement. Results : After 56 days of GCSB-5 300 administration, mechanical withdrawal thresholds were significantly increased (p<0.05), and immunohistochemical expressions of Iba1, GFAP, CGRP, and TRPV1 were reduced than other groups, but this difference was not statistically significant. Conclusion : These results indicate GCSB-5 reduces mechanical allodynia and downregulates neuroglial activity and the expressions of CGRP and TRPV1 in the spinal segments of a rat model of lumbar disc herniation.

• International Journal of Oral Biology
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• v.34 no.3
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• pp.157-164
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• 2009

We recently described a novel animal model of trigeminal neuropathic pain following compression of the trigeminal ganglion (Ahn et al., 2009). In our present study, we adapted this model using male Sprague-Dawley rats weighing between 250-260 g and then analyzed the behavioral responses of these animals following modified chronic compression of the trigeminal ganglion. Under anesthesia, the rats were mounted onto a stereotaxic frame and a 4% agar solution ($10{\mu}L$) was injected in each case on the dorsal surface of the trigeminal ganglion to achieve compression without causing injury. In the control group, the rats received a sham operation without agar injection. Air-puff, acetone, and heat tests were performed at 3 days before and at 3, 7, 10, 14, 17, 21, 24, 30, 40, 55, and 70 days after surgery. Compression of the trigeminal ganglion produced nociceptive behavior in the trigeminal territory. Mechanical allodynia was established within 3 days and recovered to preoperative levels at approximately 60 days following compression. Mechanical hyperalgesia was also observed at 7 days after compression and persisted until the postoperative day 40. Cold hypersensitivity was established within 3 days after compression and lasted beyond postoperative day 55. In contrast, compression of the trigeminal ganglion did not produce any significant thermal hypersensitivity when compared with the sham operated group. These findings suggest that compression of the trigeminal ganglion without any injury produces prolonged nociceptive behavior and that our rat model is a useful system for further analysis of trigeminal neuralgia.

• Journal of Acupuncture Research
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• v.22 no.1
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• pp.77-90
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• 2005

Objective : 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 Electroacupuncture(EA) & Acupuncture(AC) can control neuropathic pain effectively. The aim of this study is to examine if Electroacupuncture&Acupuncture at Hu-gye(SI03), Wijung(BL4O), Hu-gye(SI03) Wijung(BL40) may be effective to the neuropathic pain (mechanical allodynia cold allodynia) in a rat model of neuropathic pain. Methods : A rat model of neuropathic pain was made by injurying tibial nerve and sural nerve while common peroneal nerve was maintained. After the neuropathic surgery, we examined if the rats exhibited the behavioral signs allodynia. The allodynia was assessed by stimulating the medial malleolus with von frey filament and acetone. Three weeks after the neuropathic surgery, electroacupuncture &, acupuncture stimulation was delivered to Hu-gye(SI03), Wijung(BL40), Hu-gye(SI03) Wijung(BL40) one time a day for one week. After that we examined the withdrawal response of neuropathic rats' legs by von frey filament and acetone stimulation, c-fos and AchE(Acetylcholine esterase) in the periaqe- ductal gray(PAG) of neuropathic rats' brain. Results : 1. Electroacupuncture&Acupuncture at Hu-gye(SI03), Wijung(BL40), Hu-gye(SI03) Wijung(BL4O) significantly decreased the withdrawal response of mechanically allodynia in EA-BL40+SI03 group and AC-SI03 group as compared with control group on 6th day. 2. Electroacupuncture &Acupuncture at Hu-gye(SI03), Wijung(BL40), Hu-gye (SI03) Wijung (BL40) significantly decreased the withdrawal response of chemical allodynia(cold allodynia) in EA-SI03 group, EA-BL40+SI03 group and AC-SI03 group as compared with control group on 6th day. 3. Electroacupuncture & Acupuncture at Hu-gye ( SI03), Wijung (BL40), Hu-gye (SI03) Wijung(BL40) significantly decreased the expression of c-fos in the periaqe- ductal gray(PAC) of neuropathic rats' brain in EA-BL40+SI03 group and AC-SI03 group as compared with control group. 4. Electroacupuncture&Acupuncture at Hu-gye(SI03), Wijung(BL40), Hu-gye (SI03) Wijung(BL40) significantly decreased the expression of AchE in the periaqe- ductal gray(PAG) of neuropathic rats' brain in EA-BL40+SI03 group and AC-SI03 group as compared with control group. Conclusions : Based on the above results it is assumed that Electroacupuncture at Hu-gye(SI03) Wijung(BL40) and Acupuncture at Hu-gye(SI03) can help the treatment of neuropathic pain.

• The Korean Journal of Pain
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• v.23 no.3
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• pp.179-185
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• 2010

Background: Vincristine-induced peripheral neuropathy is a major dose limiting side effect and thus effective therapeutic strategy is required. In this study, we investigated the antinociceptive effect of memantine and morphine on a vincristine-induced peripheral neuropathy model in rats. Methods: Male Sprague-Dawley rats weighing 220-240 g were used in all experiments. Rats subsequently received daily intraperitoneal injections of either vincristine sulfate (0.1 ml/kg/day) or saline (0.1 ml/kg/day) over 12 days, immediately following behavioral testing. For assessment of mechanical allodynia, mechanical stimuli using von Frey filament was applied to the paw to measure withdrawal threshold. The effects of N-methyl-D-aspartate receptors antagonist (memantine; 2.5, 5, 10 mg/kg intraperitoneal), opioid agonist (morphine; 2.5, 5, 10 mg/kg intraperitoneal) and vehicle (saline) on vicristine-induced neuropathy were evaluated. Results: Mechanical allodynia developed over the course of ten daily injections of vincristine relative to groups receiving saline at the same time. Morphine abolished the reduction in paw withdrawal threshold compared to vehicle and produced dose-responsiveness. Only the highest dose of memantine (10 mg/kg) was able to increase paw withdrawal threshold compared to vehicle. Conclusions: Systemic morphine and memantine have an antinociceptive effect on the vincristine-induced peripheral neuropathy model in rats. These results suggest morphine and memantine may be an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

• Journal of Acupuncture Research
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• v.23 no.6
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• pp.199-205
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• 2006

Objectives : The present study was conducted to evaluate the analgesic effects of automatically controlled heating acupuncture(ACHA) using 2 different pain models(acute pain and neuropathic pain) and 2 different stimulation conditions (heating $41.5^{\cdot}C$ and heating $44.5^{\cdot}C$) in Sprague-Dawley rats. Methods : Tail flick latency(TFL) to a noxious radiant heat stimulus in lightly anesthetized rats was measured before and after ACHA stimulation for 5-min at the Zusanli(ST36) acupoint. For the neuropathic surgery, the right superior caudal trunk was resected at the level between S1 and S2 spinal nerves innervating the tail. Two weeks after the nerve injury, ACHA stimulation($41.5^{\cdot}C$ or $44.5^{\cdot}C$) was delivered to Zusanli(ST36) for 5 min. The behavioral signs of warm allodynia were evaluated by the tail immersion test (i.e. immersing the tail in warm $water(40^{\cdot}C)$ and measuring the latency to an abrupt tail movement) before and after the ACHA stimulation. Results : In the TFL test, ACHA stimulations under both the conditions above produced more potent analgesic effects than plain acupuncture(PA, acupuncture needle insertion only) and control(no treatment). In the tail immersion test, ACHA stimulations under all of the conditions had markedly relieved the warm allodynia signs. Conclusion : Automatically controlled heating acupul1cture produced analgesic effecs in acute and neuropathic pains.

• Journal of Acupuncture Research
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• v.21 no.3
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• pp.133-144
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• 2004

Background and Objective : Twirling is one of the needling methods, which is frequently used for acupuncture in oriental medicine. Some thesis about needle manipulation has been reported that needle manipulation is more effective than plain acupuncture. So we have developed the auto-controlled twirling needle(ACTN) system which is most simple style of needle manipulation. The present study was conducted to see if ACTN can enhance the antinociceptive effect of acupuncture. Methods : To investigate the analgesic effect of acupuncture we used two pain model. One is acute pain model using tail flick latency(TFL), the other is neuropathic pain model using mechanical allodynia. For TFL test, rats were lightly anesthetized with pentobarbital sodium(40 mg/kg, i.p). To produce mechanical allodynia in the rat tail, the right superior caudal trunk was resected between the S1 and S2 spinal nerves. For plain acupuncture(PA), a needle was inserted into a Zusanli(ST36) for 15min. In combining ACTN with PA, twirling needle was performed once in a second. We measured the difference of analgesic effect of only PA and ACTN on two different kinds of pain. Results and conclusion : ACTN increased TFL more than PA. (15min P<0.001, 25min P<0.01). And ACTN also reduced neuropathic pain (15min P<0.01, 25min<0.05). But PA alone can't reduce the neuropathic pain. These results indicate that ACRN had more analgesic effect than PA. The mechanism that play a key role, and the condition which produce best analgesic effect of ACTN are to be studied further.