• The Korean Journal of Pain
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• 제21권2호
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• pp.106-111
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• 2008

Background: Chronic pain after thoracotomy has been recently reproduced in a rat model that allows investigating the effect of potentially beneficial drugs that might reduce the incidence of allodynia or alleviate pain. Local anesthetics produce antinociception in normal animals and alleviate mechanical allodynia in animals with nerve injury although their mechanisms of action may differ in these situations. Our purpose of this study was to test whether the preoperative intercostal nerve block of bupivacaine could prevent the development of allodynia in a rat model of chronic postthoracotomy pain. Methods: All male Sprague-Dawley rats were anesthetized and the right 4th and 5th ribs were exposed surgically. The pleura were opened between the ribs to which a retractor was placed and was opened 10 mm in width. Retraction was maintained for one hour. Total 1 mg of 0.5% bupivacaine was injected at the intercostal nerves before (n = 17) or after (n = 16) surgery. A control group (n = 25) that underwent rib retraction did not receive any drug. Rats were tested for mechanical allodynia using calibrated von Frey filaments applied around the incision site during the three weeks following surgery. Results: The incidence of development of mechanical allodynia in the group that received intercostal injection with bupivacaine before surgery was significantly lower than that in the control group (P < 0.05). Conclusions: Preoperative intercostal nerves block around the surgical incision before thoracotomy may decrease the incidence of postthoracotomy pain syndrome.

• Journal of Acupuncture Research
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• 제22권5호
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• pp.67-77
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• 2005

Objectives : The purpose of this study is to examine if Bee Venom 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, tibial nerve and sural nerve was resected. After the neuropathic surgery, the author examined if the animals exhibited the behavioral signs of alloynia. The allodynia was assessed by stimulating the medial malleolus with von Frey filament and acetone. Three weeks after the neuropathic surgery, Bee Venom Acupuncture was injected at Hwando(GB30) one time a day for one week. After that, the author examined the withdrawl response of neuropathic rats' legs by yon 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 count in the blood of neuropathic rats. Results : The Bee Venom Acupuncture injected Hwando(GB30) decreased the withdrawl response of mechanical allodynia in BV-2, BV-3 group as compared with control group. The Bee Venom Acupuncture injected Hwando(GB30) decreased the withdrawl response of chemical allodynia(cold allodynia) in BV-2, BV-3 group as compared with control group. The Bee Venom Acupuncture injected Hwando(GB30) showed the significant difference between control group and BV-2 group, control group and BV-3 group in the c-Fos expression and U count. Conclusion : We have noticed that Bee Venom Acupuncture at Hwando(GB30) 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. Psin control using Bee Venom Acupuncture was accumulated as time goes by. This study can be used as a basic resource on a study and a treatment of pain.

• The Korean Journal of Physiology and Pharmacology
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• 제12권6호
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• pp.299-306
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• 2008

Sometimes, spinal cord injury (SCI) results in various chronic neuropathic pain syndromes that occur diffusely below the level of the injury. It has been reported that behavioral signs of neuropathic pain are expressed in the animal models of contusive SCI. However, the observation period is relatively short considering the natural course of pain in human SCI patients. Therefore, this study was undertaken to examine the time course of mechanical and cold allodynia in the hindpaw after a spinal cord contusion in rats for a long period of time (30 weeks). The hindpaw withdrawal threshold to mechanical stimulation was applied to the plantar surface of the hindpaw, and the withdrawal frequency to the application of acetone was measured before and after a spinal contusion. The spinal cord contusion was produced by dropping a 10 g weight from a 6.25 and 12.5 mm height using a NYU impactor. After the injury, rats showed a decreased withdrawal threshold to von Frey stimulation, indicating the development of mechanical allodynia which persisted for 30 weeks. The withdrawal threshold between the two experimental groups was similar. The response frequencies to acetone increased after the SCI, but they were developed slowly. Cold allodynia persisted for 30 weeks in 12.5 mm group. The sham animals did not show any significant behavioral changes. These results provide behavioral evidence to indicate that the below-level pain was well developed and maintained in the contusion model for a long time, suggesting a model suitable for pain research, especially in the late stage of SCI or for long term effects of analgesic intervention.

• The Korean Journal of Pain
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• 제26권2호
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• pp.135-141
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• 2013

Background: Although paclitaxel is a widely used chemotherapeutic agent for the treatment of solid cancers, side effects such as neuropathic pain lead to poor compliance and discontinuation of the therapy. Ethyl pyruvate (EP) is known to have analgesic effects in several pain models and may inhibit apoptosis. The present study was designed to investigate the analgesic effects of EP on mechanical allodynia and apoptosis in dorsal root ganglion (DRG) cells after paclitaxel administration. Methods: Rats were randomly divided into 3 groups: 1) a control group, which received only vehicle; 2) a paclitaxel group, which received paclitaxel; and 3) an EP group, which received EP after paclitaxel administration. Mechanical allodynia was tested before and at 7 and 14 days after final paclitaxel administration. Fourteen days after paclitaxel treatment, DRG apoptosis was determined by activated caspase-3 immunoreactivity (IR). Results: Post-treatment with EP did not significantly affect paclitaxel-induced allodynia, although it tended to slightly reduce sensitivities to mechanical stimuli after paclitaxel administration. After paclitaxel administration, an increase in caspase-3 IR in DRG cells was observed, which was co-localized with NF200-positive myelinated neurons. Post-treatment with EP decreased the paclitaxel-induced caspase-3 IR. Paclitaxel administration or post-treatment with EP did not alter the glial fibrillary acidic protein IRs in DRG cells. Conclusions: Inhibition of apoptosis in DRG neurons by EP may not be critical in paclitaxel-induced mechanical allodynia.

• The Korean Journal of Pain
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• 제18권2호
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• pp.118-123
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• 2005

Background: A nerve ligation injury may produce a tactile allodynia. The effects of intrathecally delivered lamotrigine on allodynia induced due to fifth and sixth lumbar spinal nerves ligation in rats, using lumbar intrathecal catheters were examined. Methods: Sprague-Dawley rats (body weight 160-180 g) were prepared by tightly ligating the fifth and sixth left lumbar spinal nerves, with the implantation of a chronic intrathecal catheter for drug administration. Mechanical allodynia and allodynic threshold were measured using von Frey filaments and the updown method, respectively. After the baseline hind paw withdrawal thresholds had been obtained, lamotrigine (10, 30, 100 and $300{\mu}g$) was administered intrathecally. Thereafter, the dose-response curves and 50% effective dose ($ED_{50}$) were obtained. Motor dysfunction was assessed by observing the righting/stepping reflex responses and abnormal weight bearing. Results: Intrathecal administration of lamotrigine produced a dose-dependent antiallodynic action ($ED_{50}=61.7{\mu}g$). Mild motor weakness was observed with $300{\mu}g$ lamotrigine, but no severe motor impairment was found. Conclusions: It is suggested that intrathecal lamotrigine could produce moderate antagonism of mechanical allodynia at the spinal level in a rat neuropathic pain model with minimal motor weakness.

• The Korean Journal of Physiology and Pharmacology
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• 제14권6호
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• pp.359-364
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• 2010

Many therapeutic roles have been proposed for sigma-1 receptor (Sig-1R), but the involvement of Sig-1R in neuropathic pain has currently not been well explored. The present study aimed to evaluate the anti-nociceptive effect of Sig-1R antagonist (BD1047) in a rat model of chronic compression of the dorsal root ganglion (CCD), which is a model of human foraminal stenosis and radicular pain. When stainless steel rods were inserted into the intervertebral foramen of lumbar vertebrae 4 and 5, the CCD developed reliable mechanical (from 3 day) and cold allodynia (from 1 day) as compared with the sham operation group. The spinal expressions of Sig-1R and phosphorylation of extracellular signal-regulated kinase (pERK) were significantly increased from day 3 to day 14 after CCD surgery, as is consistent with the manifestation of allodynia. The BD 1047 (10, 30, 100 mg/kg) administered on postoperative days 0~5 dose-dependently suppressed both the induction of allodynia and the elevation of the spinal pERK expression in a manner comparable with that of gabapentin (100 mg/kg). At 7 days post-CCD surgery, BD1047 (10, 30, 100 mg/kg) administration also produced anti-nociceptive effects on the mechanical and cold allodynia similar with those of gabapentin (100 mg/kg). Therefore, this data suggested that Sig-1R may play an important role in both the development and maintenance of CCD-induced neuropathy.

• The Korean Journal of Pain
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• 제35권1호
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• pp.59-65
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• 2022

Background: There is still unmet need in treating neuropathic pain and increasing awareness regarding the use of drug combinations to increase the effectiveness of treatment and reduce adverse effects in patients with neuropathic pain. Methods: This study was performed to determine the individual and combined effects of pregabalin, tianeptine, and clopidogrel in a rat model of neuropathic pain. The model was created by ligation of the L5-L6 spinal nerve in male Sprague-Dawley rats; mechanical allodynia was confirmed using von Frey filaments. Drugs were administered to the intrathecal space and mechanical allodynia was assessed; drug interactions were estimated by isobolographic or fixed-dose analyses. Results: Intrathecal pregabalin and tianeptine increased the mechanical withdrawal threshold in a dose-dependent manner, but intrathecal clopidogrel had little effect on the mechanical withdrawal threshold. An additive effect was noted between pregabalin and tianeptine, but not between pregabalin and clopidogrel. Conclusions: These findings suggest that intrathecal coadministration of pregabalin and tianeptine effectively attenuated mechanical allodynia in the rat model of neuropathic pain. Thus, pregabalin plus tianeptine may be a valid option to enhance the efficacy of neuropathic pain treatment.

• The Korean Journal of Physiology and Pharmacology
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• 제8권5호
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• pp.237-243
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• 2004

Glial cells are activated in neuropathy and play a key role in hyperalgesia and allodynia. This study was performed to determine whether minocycline could attenuate heat hyperalgesia and mechanical allodynia, and how glial cell activation and nuclear factor kappa B (NF-kappaB) were regulated by minocycline in a model of chronic constriction of sciatic nerve (CCl). When minocycline (50 mg/kg, oral) was daily administered from 1 day before to 9 days after ligation, heat hyperalgesia and mechanical allodynia were attenuated. Furthermore, when minocycline treatment was initiated 1 or 3 days after ligation, attenuation of the hypersensitive behavior was still robust. However, the effect of attenuation was less when minocycline was started from day 5. In order to elucidate the mechanism of pain attenuation by minocycline, we examined the changes of glia and NF-kappaB, and found that attenuated hyperalgesia and allodynia by minocycline was accompanied by reduced microglial activation. Furthermore, the number of NF-kappaB immunoreactive cells increased after CCI treatment and this increase was attenuated by minocycline. We also observed translocation of NF-kappaB into the nuclei of activated glial cells. These results suggest that minocycline inhibits activation of glial cells and NF-kappaB, thereby attenuating the development of behavioral hypersensitivity to stimuli.

• 한국약용작물학회지
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• 제16권3호
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• pp.183-187
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• 2008

Nerve injury can lead to neuropathic pain, which is often resistant to current analgesics and interventional therapeutic methods. Extracellular signal-regulated kinase (ERK) plays important role in the induction of neuropathic pain. We explored the antinociceptive effect of curcumin and its effect on ERK in the spinal cord in the neuropathic pain model of rats induced by chronic constriction injury (CCI) of the sciatic nerve. In injured rats, mechanical allodynia, which is one of characteristics of neuropathic pain developed and the activation of ERK in spinal cord significantly increased compared with control group. However, administration of curcumin (50 mg/kg/day p.o) for 7 days started from one day before the injury prevented the development of mechanical allodynia and increase of ERK phosphorylation. These results indicate that curcumin can be a new therapeutic agent in the treatment of neuropathic pain.

• Journal of Acupuncture Research
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• 제21권3호
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• pp.145-167
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• 2004

Objective : Neuropathic pain can be caused by a partial peripheral nerve injury. This kind of pain is usually accompanied by spontaneous burning pain, allodynia and hyperalgesia. It is not clear that scolopendrid aqua-acupuncture can control neuropathic pain effectively. The purpose of this study is to examine if scolopendrid aqua-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, tibial nerve and sural nerve was resected. After the neuropathic surgery, the author examined if the animals exhibited the behavioral signs of allodynia. The allodynia was assessed by stimulating the medial malleolus with von Frey filament and acetone. Three weeks after the neuropathic surgery, scolopendrid aqua-acupuncture was injected at Hwando(GB30) one time a day for one week. After that the author examined the withdrawl 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 count in the blood of neuropathic rats. Results & Conclusion : 1. The scolopendrid aqua-acupuncture injected at Hwando(GB30) decreased the withdrawl response of mechanical allodynia in SHA-1, SHA-2 and SAH-3 group as compared with control group. 2. The scolopendrid aqua-acupuncture injected at Hwando(GB30) decreased the withdrawl response of chemical allodynia(cold allodynia) in SHA-1, SHA-2 and SAH-3 group as compared with control group. 3. The scolopendrid aqua-acupuncture injected at Hwando(GB30) showed the significant difference between sham group and control group(p=0.01), sham and SHA-3 group(p=0.026), control group and SHA-1 group(p=0.01), control group and SHA-2 group(p=0.024) in the c-fos expression. 4. The scolopendrid aqua-acupuncture injected at Hwando(GB30) showed the significant difference between sham group and SHA-3 group(p=0.010), control group and SHA-3 group(p=0.006) in the WBC count.