• Molecules and Cells
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• v.25 no.2
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• pp.242-246
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• 2008

To assess the role of $\alpha_{1G}$ T-type $Ca^{2+}$ channels in neuropathic pain after L5 spinal nerve ligation, we examined behavioral pain susceptibility in mice lacking $Ca_{V}3.1$ (${\alpha}_{1G}{^{-/-}}$), the gene encoding the pore-forming units of these channels. Reduced spontaneous pain responses and an increased threshold for paw withdrawal in response to mechanical stimulation were observed in these mice. The ${{\alpha}_{1G}}^{-/-}$ mice also showed attenuated thermal hyperalgesia in response to both low-(IR30) and high-intensity (IR60) infrared stimulation. Our results reveal the importance of ${\alpha}_{1G}$ T-type $Ca^{2+}$ channels in the development of neuropathic pain, and suggest that selective modulation of ${\alpha}_{1G}$ subtype channels may provide a novel approach to the treatment of allodynia and hyperalgesia.

• 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

• 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.

• The Korean Journal of Pain
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• v.21 no.1
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• pp.18-26
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• 2008

Background: Because genetic manipulation is commonly accomplished in mice, mouse models for pain have advanced our understanding of the mechanisms of persistent pain. The purpose of this experimental study is to develop a mouse model for understanding incision induced postoperative pain. Methods: A longitudinal incision was made at the hindpaw of male DBA/2 mice. The withdrawal frequency(WF) from applications of von Frey filaments and the response frequency (RF) to blunt mechanical stimulation were examined in an incision group and a control grouP. The withdrawal latency (WL) to radiant heat and a pain score based on weight bearing were also measured. Tests were performed 1 day before incision, and 2 hours, 1-3 days, 5 days and 7 days after incision. Results: The WF for the strongest filament was $35.0{\pm}9.1%$ before incision and this increased to $100.0{\pm}0%$ at 2 hours and to $65.0{\pm}9.1%$ at 7 days after incision. The RF to the blunt stimulus was $4.1{\pm}4.1%$ before incision and $100.0{\pm}0.0%$ at 2 hours and $42.8{\pm}10.8%$ at 7 days after incision. The WL was $6.6{\pm}0.5sec$ before incision and $2.4{\pm}0.3sec$ at 2 hours and $5.9{\pm}0.6sec$ at 7 days after incision. The pain score increased from $1.1{\pm}0.8$ to $7.4{\pm}1.5$ at 2 days after incision. Conclusions: A mouse model of acute postoperative pain was developing by making a surgical incision in the mouse hindpaw. Mechanical hyperalgesia and allodynia lasting for several days demonstrate that this model has similarities to the human post-operative pain state. Future studies will allow us to further investigate the genetic and molecular mechanisms of incisional pain.

• Journal of Acupuncture Research
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• v.33 no.3
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• pp.1-16
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• 2016

Objectives : The objective of this study was to investigate the effects of Gentianae Macrophyllae Radix pharmacopuncture (GP) at Hwando (GB30) in neuropathic pain induced rats. Methods : Neuropathic pain in rats was induced by tibial and sural nerve transection. The rat subjects were divided into 6 groups : normal (Nor, n = 5), control (Con, n = 5), neuropathic pain- induced injected at GB30 with 1 mg/kg GP (GP-A, n = 5), 5 mg/kg GP (GP-B, n = 5) and 20 mg/kg GP (GP-C, n = 5), and neuropathic pain-induced injected with 1mg/kg Tramadol (Tramadol, n＝5). Injections were administered 2 times a week for a total of 5 treatments. After each treatment plantar withdrawal response was measured and after all 5 treatments were completed c-fos, Bax, Bcl-2, mGlu5 and leukocytes in the blood were analyzed. Results : 1. Groups GP-A, GP-B and GP-C showed a meaningful decrease in the withdrawal response of mechanical allodynia compared to the control group. 2. Groups GP-A, GP-B and GP-C showed a meaningful decrease in the expression of c-fos compared to the control group. 3. Groups GP-A and GP-C showed a meaningful increase in the expression of mGluR5 compared to the control group. 4. Groups GP-A, GP-B and GP-C showed a meaningful decrease in Bax/Bcl-2 ratio compared to the control group. Conclusion : These results suggest that Gentianae Macrophyllae Radix pharmacopuncture at Hwando (GB30) could decrease mechanical allodynia and could have analgesic and neuroprotective effects on the model of neuropathic pain.

• International Journal of Oral Biology
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• v.33 no.4
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• pp.155-162
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• 2008

The present study investigated inflammatory hypersensitivity following compression of the trigeminal ganglion in rats. Experiments were carried out on male Sprague-Dawley rats weighing 250-260 g. Under anesthesia, rats were mounted on a stereotaxic frame and injected with $8{\mu}L$ of 4% agar solution through a stainless steel injector to compress the trigeminal ganglion. In the control group, rats underwent a sham operation without agar injection. Injection sites were examined with a light micrograph after compression of the trigeminal ganglion. Air-puff thresholds (mechanical allodynia) were evaluated 3 days before surgery and 3, 7, 10, 14, 17, 21, 24, 30, and 40 days after surgery. Air-puff thresholds significantly decreased after compression of the trigeminal ganglion. Mechanical allodynia was established within 3 days and remained strong over 24 days, returning to preoperative levels approximately 40 days following compression. After subcutaneous injection of 5% formalin ($50{\mu}L$) in the compression of the trigeminal ganglion-treated rats, nociceptive scratching behavior was recorded for 9 successive 5-min internals. Injection of formalin into the vibrissa pad significantly increased the number of scratches and duration of noxious behavioral responses in sham-treated rats. Noxious behavioral responses induced by subcutaneous formalin administration were significantly potentiated in rats with trigeminal ganglion compression. These findings suggest that compression of the trigeminal ganglion enhanced formalin-induced infla-mmatory pain in the orofacial area.

• The Korean Journal of Pain
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• v.29 no.2
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• pp.86-95
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• 2016

Background: The present study was designed to examine the functional recovery following spinal cord injury (SCI) by adjusting the parameters of impact force and dwell-time using the Infinite Horizon (IH) impactor device. Methods: Sprague-Dawley rats (225-240 g) were divided into eight injury groups based on force of injury (Kdyn) and dwell time (seconds), indicated as Force-Dwell time: 150-4, 150-3, 150-2, 150-1, 150-0, 200-0, 90-2 and sham controls, respectively. Results: After T10 SCI, higher injury force produced greater spinal cord displacement (P < 0.05) and showed a significant correlation (r = 0.813) between the displacement and the force (P < 0.05). In neuropathic pain-like behavior, the percent of paw withdrawals scores in the hindpaw for the 150-4, 150-3, 150-2, 150-1 and the 200-0 injury groups were significantly lowered compared with sham controls (P < 0.05). The recovery of locomotion had a significant within-subjects effect of time (P < 0.05) and the 150-0 group had increased recovery compared to other groups (P < 0.05). In addition, the 200-0 and the 90-2 recovered significantly better than all the 150 kdyn impact groups that included a dwell-time (P < 0.05). In recovery of spontaneous bladder function, the 150-4 injury group took significantly longer recovery time whereas the 150-0 and the 90-2 groups had the shortest recovery times. Conclusions: The present study demonstrates SCI parameters optimize development of mechanical allodynia and other pathological outcomes.

• The Korean Journal of Pain
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• v.33 no.1
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• pp.30-39
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• 2020

Background: This study examined the effects of gabexate mesilate on spinal nerve ligation (SNL)-induced neuropathic pain. To confirm the involvement of gabexate mesilate on neuroinflammation, we focused on the activation of nuclear factor-κB (NF-κB) and consequent the expression of proinflammatory cytokines and inducible nitric oxide synthase (iNOS). Methods: Male Sprague-Dawley rats were used for the study. After randomization into three groups: the sham-operation group, vehicle-treated group (administered normal saline as a control), and the gabexate group (administered gabexate mesilate 20 mg/kg), SNL was performed. At the 3rd day, mechanical allodynia was confirmed using von Frey filaments, and drugs were administered intraperitoneally daily according to the group. The paw withdrawal threshold (PWT) was examined on the 3rd, 7th, and 14th day. The expressions of p65 subunit of NF-κB, interleukin (IL)-1, IL-6, tumor necrosis factor-α, and iNOS were evaluated on the 7th and 14th day following SNL. Results: The PWT was significantly higher in the gabexate group compared with the vehicle-treated group (P < 0.05). The expressions of p65, proinflammatory cytokines, and iNOS significantly decreased in the gabexate group compared with the vehicle-treated group (P < 0.05) on the 7th day. On the 14th day, the expressions of p65 and iNOS showed lower levels, but those of the proinflammatory cytokines showed no significant differences. Conclusions: Gabexate mesilate increased PWT after SNL and attenuate the progress of mechanical allodynia. These results seem to be involved with the antiinflammatory effect of gabexate mesilate via inhibition of NF-κB, proinflammatory cytokines, and nitric oxide.

• The Korean Journal of Pain
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• v.33 no.3
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• pp.216-225
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• 2020

Background: Garlic oil is a rich source of organosulfur compounds including diallyl disulfide and diallyl trisulfide. There have been studies showing the neuroprotective actions of these organosulfur compounds. However, the potential of these organosulfur compounds in neuropathic pain has not been explored. The present study was aimed at investigating the pain attenuating potential of diallyl disulfide and diallyl trisulfide in chronic constriction injury (CCI)-induced neuropathic pain in rats. The study also explored their pain-attenuating mechanisms through modulation of H₂S, brain-derived neurotrophin factor (BDNF) and nuclear factor erythroid 2-related factor 2 (Nrf2). Methods: The rats were subjected to CCI injury by ligating the sciatic nerve in four places. The development of neuropathic pain was measured by assessing mechanical hyperalgesia (Randall-Selittotest), mechanical allodynia (Von Frey test), and cold allodynia (acetone drop test) on 14th day after surgery. Results: Administration of diallyl disulfide (25 and 50 mg/kg) and diallyl trisulfide (20 and 40 mg/kg) for 14 days led to a significant reduction in pain in CCI-subjected rats. Moreover, treatment with these organosulfur compounds led to the restoration of H₂S, BDNF and Nrf2 levels in the sciatic nerve and dorsal root ganglia. Co-administration of ANA-12 (BDNF blocker) abolished pain attenuating actions as well as BDNF and the Nrf2 restorative actions of diallyl disulfide and diallyl trisulfide, without modulating H₂S levels. Conclusions: Diallyl disulfide and diallyl trisulfide have the potential to attenuate neuropathic pain in CCI-subjected rats possibly through activation of H₂S-BDNF-Nrf2 signaling pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.387-392
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• 2012

In this study, we examined the antinociceptive effect of Cyperi rhizoma (CR) and Corydalis tuber (CT) extracts using a chronic constriction injury-induced neuropathic pain rat model. After the ligation of sciatic nerve, neuropathic pain behavior such as mechanical allodynia and thermal hyperalgesia were rapidly induced and maintained for 1 month. Repeated treatment of CR or CT (per oral, 10 or 30 mg/kg, twice a day) was performed either in induction (day 0~5) or maintenance (day 14~19) period of neuropathic pain state. Treatment of CR or CT at doses of 30 mg/kg in the induction and maintenance periods significantly decreased the nerve injury-induced mechanical allodynia. In addition, CR and CT at doses of 10 or 30 mg/kg alleviated thermal heat hyperalgesia when they were treated in the maintenance period. Finally, CR or CT (30 mg/kg) treated during the induction period remarkably reduced the nerve injury-induced phosphorylation of NMDA receptor NR1 subunit (pNR1) in the spinal dorsal horn. Results of this study suggest that extracts from CR and CT may be useful to alleviate neuropathic pain.