• The Korean Journal of Pain
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• 제22권1호
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• pp.16-20
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• 2009

Background: Zaprinast is an inhibitor of phosphodiesterase 5, 6 and 9. Phosphodiesterase inhibitors could produce anti-nociceptive effects by promoting the accumulation of cGMP. We hypothesized that intrathecal zaprinast could attenuate the allodynia induced by chronic constriction injury of the sciatic nerve in rat. Methods: Sprague-Dawley rats were prepared with four loose ligations of the left sciatic nerve just proximal to the trifurcation into the sural, peroneal and tibial nerve branches. Tactile allodynia was measured by applying von Frey filaments to the lesioned hindpaw. The thresholds for the withdrawal responses were assessed. Zaprinast ($3-100{\mu}g$) was administered intrathecally by the direct lumbar puncture method to obtain the dose-response curve and the 50% effective dose ($ED_{50}$). Measurements were taken before and 15, 30, 45, 60, 90, 120, and 180 min after the intrathecal doses of zaprinast. The side effects were also observed. Results: Intrathecal zaprinast resulted in a dose-dependent antiallodynic effect. The maximal effects occurred within 15-30 min and then they gradually decreased down to the baseline level over time in all the groups. There was a dose dependent increase in the magnitude and duration of the effect. The $ED_{50}$ value was $17.4{\mu}g$ (95% confidence intervals; $14.7-20.5{\mu}g$). No severe motor weakness or sedation was observed in any of the rats. Conclusions: Intrathecally administered zaprinast produced a dose-dependent antiallodynic effect in the chronic constriction injury neuropathic pain model. These findings suggest that spinal phosphodiesterase 5, 6 and 9 may play an important role in the modulation of neuropathic pain.

• The Korean Journal of Pain
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• 제24권4호
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• pp.185-190
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• 2011

Background: Spinal nerve ligation (SNL) injury in rats produces a pain syndrome that includes mechanical and thermal allodynia. Previous studies have indicated that proinflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) play an important role in peripheral mediation of neuropathic pain, and that altered dorsal root ganglion (DRG) function and degree of DRG neuronal apoptosis are associated with spinal nerve injury. The present study was conducted to evaluate the expression of TNF-${\alpha}$ and the extent of apoptosis in the dorsal root ganglion after SNL in rats. Methods: Sprague-Dawley rats were subjected to SNL of the left L5 and L6 spinal nerves distal to the DRG and proximal to the formation of the sciatic nerve. At postoperative day 8, TNF-${\alpha}$ protein levels in the L5.6 DRG were compared between SNL and naive groups using ELISA. In addition, we compared the percentage of neurons injured in the DRG using immunostaining for apoptosis and localization of activated caspase-3. Results: SNL injury produced significant mechanical and cold allodynia throughout the 7-day experimental period. TNF-${\alpha}$ protein levels were increased in the DRG in rats that had undergone SNL ($12.7{\pm}3.2$ pg/100 ${\mu}g$, P < 0.001) when compared with naive rats ($4.1{\pm}1.4$ pg/100 ${\mu}g$). The percentage of neurons or satellite cells co-localized with activated caspase-3 were also significantly higher in rats with SNL than in naive rats (P < 0.001, P < 0.05, respectively). Conclusions: SNL injury produces mechanical and cold allodynia, as well as TNF-${\alpha}$ elevation and apoptosis in the DRG.

• The Korean Journal of Pain
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• 제14권1호
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• pp.123-125
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• 2001

A 50-year-old female patient developed severe right neck and upper extremity pain, hyperesthesia and allodynia during cervical epidural block. Her pain was diagnosed as neuropathic nature. She was treated with repeated stellate ganglion block (SGB) and electrical stimulation (EST). After 3 weeks of treatment, symptomatic relief was achieved, but a mild degree of hyperesthesia and motor weakness was remained. However, she refused all treatment. So treatment was stopped. In a follow-up done, 15 weeks after the nerve injury, she had recovered without complications.

• 한국감성과학회:학술대회논문집
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• 한국감성과학회 2004년도 추계학술대회 논문집
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• pp.44-44
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• 2004

• Journal of Korean Neurosurgical Society
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• 제59권2호
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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.

• The Korean Journal of Pain
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• 제23권3호
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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.

• The Korean Journal of Pain
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• 제21권1호
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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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• 제23권6호
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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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• 제33권3호
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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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• 제34권3호
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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.