• The Korean Journal of Pain
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• v.37 no.4
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• pp.310-319
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• 2024

Background: This study aimed to investigate the analgesic and preventive effect of low-level laser therapy (LLLT) on the incisional pain model and spinal nerve ligation (SNL) model in rats and identify the possible mechanisms of action. Methods: Male Sprague-Dawley rats were used, divided into different treatment groups. The single application group received LLLT before or after skin incision or SNL. The consecutive application group received LLLT for six consecutive days post-incision, three days pre-incision, or three consecutive days pre-SNL. The control group underwent skin incision or SNL without LLLT. The von Frey test was used to quantify the pain associated with mechanical allodynia. Pro-inflammatory cytokine level and alterations in nerve growth factor (NGF) expression were measured by using ELISA and immunohistochemistry, respectively in the skin, muscle of the paw, and spinal cord dorsal horn (SCDH). Results: In the incisional pain model, LLLT showed significant analgesic and preventive effect. LLLT ameliorated SNL-induced mechanical allodynia but LLLT had no preventive effect. LLLT decreased interleukin-1β (IL-1β) expression levels in the skin, muscle, and SCDH and reduced the optical density of skin and spinal cord NGF in the incisional pain model. Conclusions: LLLT alleviated incisional pain and neuropathic pain caused by SNL in rats, and reduced the levels of IL-1β and NGF in the peripheral tissue and SCDH in the incisional pain model. LLLT might be effective in patients with post-operative pain and peripheral neuropathic pain.

• Journal of Acupuncture Research
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• v.22 no.6
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• pp.27-36
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• 2005

Introduction : The aim of the study is to investigate the suppressive action of electroacupuncture on cold alloynia development in the rat model of neuopathic pain. Methods : To produce neuropathic pain, the right superior caudal trunk was resected $1{\sim}2\;mm$ between S1 and S2 spinal nerves. The rats were divided into control and four electroacupuncture groups: Two electroacupuncture groups were given 2 Hz or 100 Hz electroacupuncture for 20 minutes everyday after the sacral nerve injury. Other two electroacupuncture groups were given 2 Hz or 100 Hz electroacupuncture for 20 minutes just one session at one hour after the sacral nerve injury. The right point of Joksamni (ST36) was applied for electroacupuncture. The control group was induced neuropathic pain without electroacupuncture. The cold allodynia was assessed by immersing the tail in $4^{\circ}C$ water. The latency to an abrupt tail movement after rat tail immersion was measured with a cut-off time of 15 sec at 4th, 7th and 14th day after the sacral nerve injury. Results : The results were as follows; 1. At 4th experimental day, there were no significant differences between 2 Hz or 100 Hz electroacupuncture groups and the control group. 2. At 7th experimental day, everyday 2 Hz or 100 Hz electroacupuncture groups showed significant differences compared with the control group. But There were no significant differences between 2 Hz and 100 Hz electroacupuncture groups. 3. At 14th experimental day, everyday 2 Hz electroacupuncture group showed significant differences compared with the control group. But everyday 100 Hz electroacupuncture group showed no significant difference compared with the control group and everyday 2 Hz electroacupuncture group. 4. There were no significant differences between the control and 2 Hz or 100 Hz electroacupuncture groups which were done just one session at one hour after the surgery. 5. Everyday 2 Hz electroacupuncture group showed significant differences in the one session of the 100 Hz electroacupuncture group. Conclusion : Everyday 2 Hz electroacupuncture exerts a suppressive action on cold allodynia development in the rat model of neuropathic pain.

• Journal of Acupuncture Research
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• v.31 no.4
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• pp.57-70
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• 2014

Objectives : The purpose of this study is to examine if Clematidis Radix(CR) pharmacopuncture may be effective to the neuropathic pain(mechanical allodynia) in a rat model of neuropathic pain. Methods : To produce the model of neuropathic, L5 spinal nerve was ligated by 6-0 silk thread. After neuropathic surgery, the author examined if the animals exhibited the plantar withdrawal response of allodynia. The plantar withdrawal response was assessed by dynamic plantar aesthesiometer three days after the neuropathic surgery, CR pharmacopuncture was injected at $BL_{23}$ 1time/week for 6 weeks. After that, the author examined the plantar withdrawal response of rats' leg by dynamic plantar aesthesiometer. And also the author examined mGluR5, Bax, Bcl-2, Bax/Bcl-2 ratio in spinal cord, and c-Fos. Also the author observed the change of aspartate aminotransferase(AST), alanine aminotransferase(ALT) count in the blood serum of neuropathic rats. Results : 1. The withdrawal response of allodynia decreased in the PT3, PT4 group as compared with control group. 2. The mGluR5 increased in the PT1, PT2, PT3, and PT4 group. 3. The Bax and Bax/Bcl-2 ratio decreased in the PT4 group. 4. The c-Fos increased in the PT1 group, and decreased in the PT4 group. 5. The changes of AST in blood serum decreased in the every group excluded control group and the changes of ALT in blood serum isn't shown the signigicant change. Conclusions : These results are suggested that CR pharmacopuncture at BL23 decreased mechanical allodynia, can act on anti-apoptotic, neuroprotective effects and liver fuction in the model of neuropathic pain.

• 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.22 no.1
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• pp.21-27
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• 2009

Background: The neuropathic pain arising from nerve injury is difficult to treat and the therapeutic effects of opioid drugs remain debatable. Agonists acting at the ${\alpha}_2$ adrenergic and opioid receptors have analgesic properties and they act synergistically when co-administered in the spinal cord. The lack of subtype-selective pharmacological agents has previously impeded the synergistic effects that are mediated by the adrenergic receptor subtypes. Methods: We created neuropathic pain model by ligating the L5 spinal nerve in Sprague-Dawley rats (n = 18). We divided the rats into three groups (n = 6 for each group), and we administered intraperitoneal morphine (1 mg/kg, 3 mg/kg, 5 mg/kg) and then we measured the mechanical allodynia with using von-Frey filaments for 8 hours. We then injected morphine (5 mg/kg) intraperitoneally, twice a day for 2 weeks. We measured the tactile and cold allodynia in the morphine group (n = 9) and the saline group (n = 9). After 2 weeks, we decapitated the rats and harvested the spinal cords at the level of lumbar enlargement. We compared the ${\alpha}_2$ subtype mRNA expression with that of control group (n = 6) by performing real time polymerase chain reaction (RTPCR). Results: Intraperitoneal morphine reduced the neuropathic pain behavior in the dose-dependent manner. Chronic morphine administration showed an antiallodynic effect on the neuropathic pain rat model. The rats did not display tolerance or hyperalgesia. The expression of the mRNAs of the ${\alpha}_{2A}$, ${\alpha}_{2B}$, ${\alpha}_{2C}$ subtypes decreased, and morphine attenuated this effect. But we could not get statistically proven results. Conclusions: Systemic administration of morphine can attenuate allodynia during both the short-term and long-term time course. Morphine has an influence on the expression of ${\alpha}_2$ receptor subtype mRNA. Yet we need more research to determine the precise effect of morphine on the ${\alpha}_2$ subtype gene expression.

• 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.

• The Korean Journal of Pain
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• v.33 no.1
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• pp.23-29
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• 2020

Background: Neuropathic pain (NP) is considered a clinically incurable condition despite various treatment options due to its diverse causes and complicated disease mechanisms. Since the early 2000s, multipotent human mesenchymal stem cells (hMSCs) have been used in the treatment of NP in animal models. However, the effects of hMSC injections have not been studied in chronic post-ischemia pain (CPIP) mice models. Here, we investigated whether intrathecal (IT) and intrapaw (IP) injections of hMSCs can reduce mechanical allodynia in CPIP model mice. Methods: Seventeen CPIP C57/BL6 mice were selected and randomized into four groups: IT sham (n = 4), IT stem (n = 5), IP sham (n = 4), and IP stem (n = 4). Mice in the IT sham and IT stem groups received an injection of 5 μL saline and 2 × 10⁴ hMSCs, respectively, while mice in the IP sham and IP stem groups received an injection of 5 μL saline and 2 × 10⁵ hMSCs, respectively. Mechanical allodynia was assessed using von Frey filaments from pre-injection to 30 days post-injection. Glial fibrillary acidic protein (GFAP) expression in the spinal cord and dorsal root ganglia were also evaluated. Results: IT and IP injections of hMSCs improved mechanical allodynia. GFAP expression was decreased on day 25 post-injection compared with the sham group. Injections of hMSCs improved allodynia and GFAP expression was decreased compared with the sham group. Conclusions: These results suggested that hMSCs may be also another treatment modality in NP model by ischemia-reperfusion.

• The Korean Journal of Pain
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• v.12 no.2
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• pp.246-249
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• 1999

Postherpetic neuralgia (PHN) is defined as the persistence of pain after recovery from herpes zoster (HZ), when the rash has healed, usually after about 4 weeks. PHN is the most feared complication of herpes zoster and remains one of the most common and intractable chronic pain disorders. Recent evidence has shed some light on the possible mechanism of pain, and on the prophylactic and treatment approaches to PHN, but there is no secure therapy. This report is a case of a 70-year-old male with PHN, affecting the 8th to 10th thoracic dermatomes. Patient complains of allodynia and hyperalgesia on the affected skins. After sympathectomy, antidepressant, anticonvulsant, and capsaicin ointment application, much pain relief was achieved, but allodynia remained at the subcostal area about $7\times3 cm^2$ in size. We decided to remove the painful area. Skin excision was done under local anesthesia. After skin excision, the pain was decreased and patient did not complain of pain for 10 months.