• The Korean Journal of Pain
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• v.20 no.2
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• pp.106-110
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• 2007

Background: A phosphodiesterase 5 inhibitor, sildenafil, has been effective against nociception. Several lines of evidence have demonstrated the role of the GABAergic pathway in the modulation of nociception. The impact of the GABA receptors on sildenafil was studied using the formalin test at the spinal level. Methods: Male SD rats were prepared for intrathecal catheterization. The formalin test was induced by subcutaneous injection of formalin solution. The change in the activity of sildenafil was examined after pre-treatment with GABA receptor antagonists ($GABA_A$ receptor antagonist, bicuculline; $GABA_B$ receptor antagonist, saclofen). Results: Intrathecal sildenafil dose-dependently attenuated the flinching observed during phase 1 and 2 in the formalin test. The antinociceptive effect of sildenafil was reversed by the $GABA_B$ receptor antagonist (saclofen) but not by the $GABA_A$ receptor antagonist (bicuculline) in both phases. Conclusions: Intrathecal sildenafil suppressed acute pain and the facilitated pain state. The antinociception of sildenafil is mediated via the $GABA_B$ receptor, but not the $GABA_A$ receptor, at the spinal level.

• The Korean Journal of Pain
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• v.20 no.1
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• pp.21-25
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• 2007

Background: Intrathecal sildenafil has produced antinociception by increasing the cGMP through inhibition of phosphodiesterase 5. Spinal opioid receptor has been reported to be involved in the modulation of nociceptive transmission. The aim of this study was to examine the role of opioid receptor in the effect of sildenafil on the nociception evoked by formalin injection. Methods: Rats were implanted with lumbar intrathecal catheters. Formalin testing was used as a nociceptive model. Formalin-induced nociceptive behavior (flinching response) was observed. To clarify the role of the opioid receptor for the analgesic action of sildenafil, naloxone was administered intrathecally 10 min before sildenafil delivery, and formalin was then injected 10 min later. Results: Intrathecal sildenafil produced dose-dependent suppression of flinches in both phases during the formalin test. Intrathecal naloxone reversed the analgesic effect of sildenafil in both phases. Conclusions: Sildenafil is active against the nociceptive state that's evoked by a formalin stimulus, and the opioid receptor is involved in the analgesic action of sildenafil at thespinal level.

• The Korean Journal of Pain
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• v.32 no.2
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• pp.87-96
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• 2019

Background: This study was performed in order to examine the effect of intrathecal sec-O-glucosylhamaudol (SOG), an extract from the root of the Peucedanum japonicum Thunb., on incisional pain in a rat model. Methods: The intrathecal catheter was inserted in male Sprague-Dawley rats (n = 55). The postoperative pain model was made and paw withdrawal thresholds (PWTs) were evaluated. Rats were randomly treated with a vehicle (70% dimethyl sulfoxide) and SOG ($10{\mu}g$, $30{\mu}g$, $100{\mu}g$, and $300{\mu}g$) intrathecally, and PWT was observed for four hours. Dose-responsiveness and ED50 values were calculated. Naloxone was administered 10 min prior to treatment of SOG $300{\mu}g$ in order to assess the involvement of SOG with an opioid receptor. The protein levels of the ${\delta}$-opioid receptor, ${\kappa}$-opioid receptor, and ${\mu}$-opioid receptor (MOR) were analyzed by Western blotting of the spinal cord. Results: Intrathecal SOG significantly increased PWT in a dose-dependent manner. Maximum effects were achieved at a dose of $300{\mu}g$ at 60 min after SOG administration, and the maximal possible effect was 85.35% at that time. The medial effective dose of intrathecal SOG was $191.3{\mu}g$ (95% confidence interval, 102.3-357.8). The antinociceptive effects of SOG ($300{\mu}g$) were significantly reverted until 60 min by naloxone. The protein levels of MOR were decreased by administration of SOG. Conclusions: Intrathecal SOG showed a significant antinociceptive effect on the postoperative pain model and reverted by naloxone. The expression of MOR were changed by SOG. The effects of SOG seem to involve the MOR.

• The Korean Journal of Pain
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• v.27 no.3
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• pp.297-300
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• 2014

This report describes the long term safety and efficacy of intrathecal therapy using Sufentanil for the management of chronic intractable neuropathic pain in 12 chronic pain patients. Standardized psychological screening was used to determine treatment suitability. Evaluation data included the Visual Analog Scale (VAS), Wong-Baker Faces Scale, Brief Pain Inventory (BPI), Disability of Arm, Shoulder, and Hand (DASH), McGill Quality of Life Questionnaire, and complications (granulomas, toxicity, withdrawal, or deaths). SPSS version 18 was used for data analysis. Pre- and post- treatment BPI measures and pain scale scores showed a statistically significant difference. There were no complications directly related to drug toxicity, nor drug withdrawals, granulomas, or deaths. Intrathecal therapy with Sufentanil therapy offers a good treatment alternative for those cases that have failed both surgery and standard pain treatment. Strict patient selection based on psychological screening, control of co-morbidities, a proper pain management may contribute to successful outcome.

• The Korean Journal of Pain
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• v.25 no.2
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• pp.126-129
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• 2012

Opioid analgesia is the primary pharmacologic intervention for managing pain. However, opioids can cause various adverse effects including pruritus, nausea, constipation, and sedation. Respiratory depression is the most fatal side effect. Therefore, cautious monitoring of respiratory status must be done after opioid administration. Here, we report a patient who suffered from respiratory depression with deep sedation and aspiration pneumonitis after intrathecal morphine administration.

• The Korean Journal of Pain
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• v.18 no.2
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• pp.107-112
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• 2005

Background: Nerve ligation injury may produce mechanical allodynia, but this can be reversed after an intrathecal administration of adenosine analogues. In many animal and human studies, ATP-sensitive potassium channel blockers have been known to reverse the antinociceptive effect of various drugs. This study was performed to evaluate the mechanical antiallodynic effects of spinal R-PIA (Adenosine A1 receptor agonist) and the reversal of these effects due to pretreatment with glibenclamide (ATP-sensitive potassium channel blocker). Thus, the relationship between the antiallodynic effects of R-PIA and ATP-sensitive potassium channel were investigated in a neuropathic model. Methods: Male Sprague Dawley rats were prepared by tightly ligating the left lumbar 5th and 6th spinal nerves and implantation of a chronic lumbar intrathecal catheter for drug administration. The mechanical allodynia was measured by applying von Frey filaments ipsilateral to the lesioned hind paw. And the thresholds for paw withdrawal assessed. In study 1, either R-PIA (0.5, 1 and $2{\mu}g$) or saline were administered intrathecally for the examination of the antiallodynic effect of R-PIA. In study 2, glibenclamide (2, 5, 10 and 20 nM) was administered intrathecally 5 min prior to an R-PIA injection for investigation of the reversal of the antiallodynic effects of R-PIA. Results: The antiallodynic effect of R-PIA was produced in a dose dependent manner. In study 1, the paw withdrawal threshold was significantly increased with $2{\mu}g$ R-PIA (P < 0.05). In study 2, the paw withdrawal threshold with $2{\mu}g$ R-PIA was significantly decreased almost dose dependently by intrathecal pretreatment of 5, 10 and 20 nM glibenclamide (P < 0.05). Conclusions: These results demonstrated that an intrathecal injection of ATP-sensitive potassium channel blockers prior to an intrathecal injection of adenosine A1 receptors agonist had an antagonistic effect on R-PIA induced antiallodynia. The results suggest that the mechanism of mechanical antiallodynia, as induced by an intrathecal injection of R-PIA, may involve the ATP-sensitive potassium channel at both the spinal and supraspinal level in a rat nerve ligation injury model.

• The Korean Journal of Pain
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• v.18 no.2
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• pp.133-137
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• 2005

Background: Cannabinoids have shown antinociceptive action. The aims of this study were to examine the effect of chronic infusion of a cannabinoids receptors agonist (WIN 55,212-2) for thermal nociception at the spinal level, and to also observe the development of toxicity. Methods: Male Sprague-Dawley rats were implanted with lumbar intrathecal catheters with the nociceptive response (withdrawal response latency) determined by exposing the plantar surface of the hindpaw to radiant heat. Initially, the effect of intrathecal WIN 55,212-2 was evaluated followed by the change in the effect at 1, 2, 3 and 4 weeks after repeated infusion. Finally, the histopathological findings were assessed 1 and 4 weeks following the infusion of WIN 55,212-2. Results: Intrathecal WIN 55,212-2 was found to produce a limited antinociception during the thermal test. %MPE of WIN 55,212-2 at 1, 2, 3, and 4 weeks after infusion was not different from each other. No abnormal pathological findings were observed following a chronic intrathecal infusion of WIN 55,212-2. Conclusions: WIN 55,212-2, a cannabinoids receptors agonist, may be useful in the management of thermal nociception, without changing the effectiveness or causing the toxicity following a chronic infusion at the spinal level.

• The Korean Journal of Pain
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• v.12 no.1
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• pp.1-7
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• 1999

Background: To study the role of spinal alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in pain behaviors caused by mild burn, we examined the effect of intrathecal administered ACEA 2085, which has been recently characterized as a high potency competitive AMPA receptor antagonist, on the thermal hyperalgesia state induced by mild burn. Methods: A thermal injury was induced by applying the left hind paw to a thermal surface ($52.5^{\circ}C$) for 45 sec. Thermal escape latency of the hind paw was determined using an underglass thermal stimulus. Thirty min after thermal injury, the paw withdrawal latency (PWL) in injured paw of all groups fell from 10~12 sec to 5~7 sec. At that time, ACEA 2085 (0.01~0.1 mcg) and 6-cyano-7-nitroquinoxalinedione (CNQX, 1~30 mcg) were injected through intrathecal heters in rats with mild burn injury on the right hindpaw. And then, PWL were measured in the both hindpaw every 30 minutes for about three hours. Results: The intrathecal injection of ACEA 2085 produced a dose dependent reversal of the hyperalgesia in the right hindpaw and more potent than CNQX, but had no effect upon the response latency of the normal left hind paw even at the largest doses. All effects were observed at doses that had no significant effect upon motor function. Conclusions: Intrathecal ACEA 2085, highly selective AMPA receptor antagonist produce a dose- dependent reversal of the thermal hyperalgesia evoked mild burn injury. These results suggested that spinal AMPA receptor play an important role in the hyperalgesia induced by mild burn injury.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.33-41
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• 1993

Central analgesic effect of capsaicin was assessed by the tail flick reflex (TFR) test, using male Sprague-Dawley rats under anesthesia with pentobarbital sodium (induction with 40 mg/kg and maintenance with $4{\sim}8\;mg/kg/hr$). Level of norepinephrine in the spinal cord was also measured. Capsaicin, $35{\sim}150\;{\mu}g$, was injected intrathecally, and the TFR latency was measured before, 10, 30, and 60 minutes after the drug administration. TFR latency was increased 100% or more immediately by intrathecal capsaicin, from 2.9 seconds to the maximum of 7.0 seconds at 10 minute after the drug; P<0.01. The increase in TFR latency was maintained during the course of experiment of 2 hours. Concomitant reduction of NE content in the spinal cord was observed; from 16 ng/mg protein to 7 ng/mg protein. On the other hand, subcutaneous injection of capsaicin of 50 mg/kg did not change the TFR latency although the NE content reduced similarly to the case of intrathecal injection. Pretreatment of the animal with 0.5 mg/kg of MK-801 reversed the increase of TFR latency and NE reduction induced by intrathecal capsaicin. These results suggest that capsaicin causes analgesia at the spinal cord level by activating the excitatory amino acid-NE-dorsal horn interneurons axis of the descending inhibitory pain modulation pathway.

• The Korean Journal of Pain
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• v.20 no.2
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• pp.100-105
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• 2007

Background: Ginseng has been used to manage various types of pain in folk medicine. This study characterized the effect of treatment with intrathecal ginsenosides, the active components of ginseng in a postoperative pain model. Methods: Male Sprague-Dawley rats were implanted with lumbar intrathecal catheters. An incision was made in the plantar surface of the hindpaw. Withdrawal thresholds following the application of a von Frey filament to the wound site were measured. To determine the role of the opioid or GABA receptors following treatment with the ginsenosides, naloxone, bicuculline (a $GABA_A$ receptor antagonist), and saclofen (a $GABA_B$ receptor antagonist) were administered intrathecally 10 min before the delivery of the ginsenosides and the changes of the withdrawal thresholds after application of the von Frey filament were Observed. Results: Treatment with the intrathecal ginsenosides increased the withdrawal threshold in a dose dependent manner. Pre-treatment with intrathecal naloxone reversed the antinociceptive effect of the ginsenosides. However, pre-treatment with intrathecal bicuculline and saclofen failed to have an effect on the activity of the ginsenosides. Conclusions: These results suggest that ginsenosides are effective to alleviate the postoperative pain evoked by paw incision. The opioid receptor, but not GABA receptors, may be involved in the antinociceptive action of the ginsenosides at the spinal level.