• Journal of Acupuncture Research
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• v.24 no.5
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• pp.137-150
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• 2007

Objectives : To find effects of acupuncture, electro-acupuncture, low level He-Ne laser therapy(LLLT) at $TE_5$, $GB_{41}$ in the neuropathic pain. We made experiment on rats ligated L5 spinal nerve like general herniation of nucleus pulposus(HNP). Methods : A model of neuropathic pain was made by isolating Left 5th lumbar spinal nerve of rats. Three days after the neuropathic surgery, acupuncture and LLLT, electro-acupuncture was injected at $TE_5$, $GB_{41}$ one time a day for a week. Each group was divided two. one is opposite side performed the surgery which is right, another is left side performed the surgery. After that, the author examined the withdrawal response of neuropathic rats' legs by van Frey filament and acetone stimulation. And also the author examined c-Fos, Nociceptin and KOR-3 in the midbrain central gray of neuropathic rats. Results : As we have observed the effect of mechanical allodynia, LT-R group were diminished on 6th day compared with control group, EA-L group, EA-R group and LT-L group were diminished on 7th day compared with control group. As we have observed the effect of cold allodynia, EA-R group were diminished on 6th day, 7th day compared with control group. As we have observed the effect of activity of c-Fos in the central gray part, EA-R group and LT-R group were diminished compared with control group. As we have observed the effect of activity of Nociceptin in the central gray part, EA-R group were a little increased compared with control group but it is not reliability. As we have observed the effect of activity of KOR-3 in the central gray part, EA-R group were significantly increased compared with control group. Conclusions : We have noticed that effect of acupuncture at opposite side of sickness and powerful stimulation could be more effective, because of EA-R group have more controllable effect all test we have done on the other hand EA-L group have only effect on mechanical allodynia. This study can be used in clinical therapy for neuropathic pain. But it is not reliability that Nociceptin have effectively to control pain. Therefore We have to follow up about that.

• The Korean Journal of Pain
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• v.27 no.4
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• pp.326-333
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• 2014

Background: Nefopam is a centrally acting non-opioid analgesic agent. Its analgesic properties may be related to the inhibitions of monoamine reuptake and the N-methyl-D-aspartate (NMDA) receptor. The antinociceptive effect of nefopam has been shown in animal models of acute and chronic pain and in humans. However, the effect of nefopam on diabetic neuropathic pain is unclear. Therefore, we investigated the preventive effect of nefopam on diabetic neuropathic pain induced by streptozotocin (STZ) in rats. Methods: Pretreatment with nefopam (30 mg/kg) was performed intraperitoneally 30 min prior to an intraperitoneal injection of STZ (60 mg/kg). Mechanical and cold allodynia were tested before, and 1 to 4 weeks after drug administration. Thermal hyperalgesia was also investigated. In addition, the transient receptor potential ankyrin 1 (TRPA1) and TRP melastatin 8 (TRPM8) expression levels in the dorsal root ganglion (DRG) were evaluated. Results: Pretreatment with nefopam significantly inhibited STZ-induced mechanical and cold allodynia, but not thermal hyperalgesia. The STZ injection increased TRPM8, but not TRPA1, expression levels in DRG neurons. Pretreatment with nefopam decreased STZ-induced TRPM8 expression levels in the DRG. Conclusions: These results demonstrate that a nefopam pretreatment has strong antiallodynic effects on STZ-induced diabetic rats, which may be associated with TRPM8 located in the DRG.

• Korean Journal of Acupuncture
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• v.36 no.1
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• pp.52-62
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• 2019

Objectives : The objective of this study was to investigate the effects of Zingiberis Rhizoma Pharmacopuncture(ZP) at GB30 and ST36 in neuropathic pain induced SD rats by the block of Transient Receptor Potential Vanilloid 1(TRPV1). Methods : Neuropathic pain in rats was induced by tibial and common peroneal nerve transection of right leg. The rat subjects were divided into 6 groups : normal(Nor, n=5), control(Con, n=5), neuropathic pain plus 2 mg/kg ZP injection at GB30 and ST36(ZP-A, n=5), 10 mg/kg ZP(ZP-B, n=5), 20 mg/kg ZP(ZP-C, n=5) and 0.45 mg/kg Tramadol(Tra, n=5). Three days after the surgery, injections were administered once a day for 17 days. Withdrawal response of neuropathic rats' legs were measured by stimulating the paw of Right leg with von frey filament, acetone and radient heat on day 3, 7, 11, 15, 19 after surgery. After all treatments were completed, c-Fos in the midbrain central gray and TRPV1 & TRPA1 of DRG(L5) were analyzed. Results : Groups ZP-B and ZP-C showed a meaningful decrease in the withdrawal response of mechanical allodynia, thermal hyperalgesia and cold allodynia compared to the control group(p<0.05, p<0.01, p<0.001). Groups ZP-B and ZP-C showed a meaningful decrease in the expression of c-fos and TRPV1 protein level compared to the control group(p<0.05, p<0.01, p<0.001). Conclusions : These results suggest that Zingiberis Rhizoma Pharmacopuncture at GB30 and ST36 could decrease mechanical & cold allodynia and thermal hyperalgesia by block the TRPV1 on the model of neuropathic pain.

• The Korean Journal of Pain
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• v.28 no.4
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• pp.236-243
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• 2015

Background: Chemotherapy-induced peripheral neuropathy is a major side effect of anti-cancer drugs, and our knowledge of its mechanisms is lacking. Several models for chemotherapy-induced neuropathy have been introduced. However, the outcomes of these models differ significantly among laboratories. Our object was to create a model of chemotherapy-induced neuropathy in rats with cancer. Methods: Female Sprague-Dawley rats were used. Mammary rat metastasis tumor (MRMT-1) cells were implanted subcutaneously in rats. Chemotherapy-induced peripheral neuropathy was induced by injection of cisplatin once a day for four days. The responses to mechanical and thermal stimuli were examined using von Frey filaments, acetone, and radiant heat. Results: Cisplatin (2 mg/kg/day) produced mechanical allodynia, while it did not induce cold allodynia or thermal hyperalgesia. This dose of cisplatin could work successfully against cancer. Body weight loss was not observed in cisplatin-treated rats, nor were other abnormal behaviors noted in the same rats. Conclusions: Repeated injection of intraperitoneal cisplatin induced peripheral neuropathic pain in rats. Thus, this type of rat model has broad applicability in studies related to searching for the mechanism of cisplatin-induced mechanical allodynia and agents for the treatment of neuropathic pain.

• Journal of Acupuncture Research
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• v.23 no.5
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• pp.23-29
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• 2006

Objectives : The present study was conducted to evaluate the effects of automatically controlled rotating acupuncture (ACRA) on thermal allodynia in neuropathic pain rats, and to examine whether the endogenous opioid system mediates the effects of ACRA. Methods : 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, ACRA stimulation with 4 different stimulation conditions (i.e., angle and frequency of rotation: 90o+1Hz, 90o+1/4Hz, 360o+/1Hz, and 360o+1/4Hz) was delivered to the Zusanli (ST36) acupoint for 15 min. The behavioral signs of thermal allodynia were evaluated by the tail immersion test (i.e., immersing the tail in cold $(4^{\circ}C)$ or warm $(4^{\circ}C)$ water and measuring the latency to an abrupt tail movement) before and after the stimulation. In an additional set of experiments, we examined the effects of naloxone (opioid Results : ACRA stimulations under all of the conditions above significantly relieved thermal antagonist, 2mg/kg, i.p.) on the action of ACRA stimulation. allodynia. There is no difference in the anti-allodynic effects among the 4 stimulation conditions. In addition, the effect of ACRA on thermal allodynia was reversed by naloxone pretreatment. Conclusion : These results indicate that ACRA stimulations have relieving effects on thermal allodynia in neuropathic pain rats, irrespective of stimulation parameters, and that this is mediated by the endogenous opioid system.

• The Korean Journal of Pain
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• v.25 no.1
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• pp.7-15
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• 2012

Background: Neuropathic pain is a chronic pain due to disorder in the peripheral or central nervous system with different pathophysiological mechanisms. Current treatments are not effective. Analgesic drugs combined can reduce pain intensity and side effects. Here, we studied the analgesic effect of nimesulide, nefopam, and morphine with different mechanisms of action alone and in combination with other drugs in chronic constriction injury (CCI) model of neuropathic pain. Methods: Male Wistar rats (n = 8) weighing 150-200 g were divided into 3 different groups: 1- Saline-treated CCI group, 2- Saline-treated sham group, and 3- Drug-treated CCI groups. Nimesulide (1.25, 2.5, and 5 mg/kg), nefopam (10, 20, and 30 mg/kg), and morphine (1, 3, and 5 mg/kg) were injected 30 minutes before surgery and continued daily to day 14 post-ligation. In the combination strategy, a nonanalgesic dose of drugs was used in combination such as nefopam + morphine, nefopam + nimesulide, and nimesulide + morphine. Von Frey filaments for mechanical allodynia and acetone test for cold allodynia were, respectively, used as pain behavioral tests. Experiments were performed on day 0 (before surgery) and days 1, 3, 5, 7,10, and 14 post injury. Results: Nefopam (30 mg/kg) and nimesulide (5 mg/kg) blocked mechanical and thermal allodynia; the analgesic effects of morphine (5 mg/kg) lasted for 7 days. Allodynia was completely inhibited in combination with nonanalgesic doses of nefopam (10 mg/kg), nimesulide (1.25 mg/kg), and morphine (3 mg/kg). Conclusions: It seems that analgesic drugs used in combination, could effectively reduce pain behavior with reduced adverse effects.

• 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.

• 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.

• Proceedings of the Korean Society for Emotion and Sensibility Conference
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• 2004.11a
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• pp.44-44
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• 2004

• 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.