• The Korean Journal of Pain
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• v.26 no.2
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• pp.125-129
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• 2013

Background: 5-hydroxytryptamine 3 (5-HT3) receptors have been known to be associated with the modulation of nociceptive transmission. However, it is uncertain whether 5-HT3 plays a role in the antinociceptive or pronociceptive pathway for incisional pain. In this study, we evaluated the effects of palonosetron, a 5-HT3 receptor antagonist, on incisional pain in rats when administered intrathecally or intraplantarly. Methods: An intrathecal catheter was implanted through the cisterna magna and placed in the intrathecal space of rats. An incision in the plantaris muscle of the right hind paw was done under anesthesia with sevoflurane. Withdrawal thresholds were evaluated with the von Frey filament after 2 hours. Palonosetron (0.5 and 0.1 ${\mu}g$ intrathecally; 0.5 ${\mu}g$ intraplantarly) was administered and the thresholds were observed for 4 hours. Results: Mechanical hypersensitivity developed after the incision. Intrathecal palonosetron (0.5 ${\mu}g$ and 0.1 ${\mu}g$) did not alter the paw withdrawal threshold. Intraplantar palonosetron (0.5 ${\mu}g$) also did not change the paw withdrawal threshold. Conclusions: Intrathecal and intraplantar palonosetron (0.5 ${\mu}g$) had no effect on modulating the mechanical hypersensitivity in the incisional pain model of rats.

• The Korean Journal of Pain
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• v.35 no.2
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• pp.173-182
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• 2022

Background: Neurokinin-1 (NK1) and calcitonin gene-related peptide (CGRP) play a vital role in pain pathogenesis, and these proteins' antagonists have attracted attention as promising pharmaceutical candidates. The authors investigated the anti-nociceptive effect of co-administration of the CGRP antagonist and an NK1 antagonist on pain models compared to conventional single regimens. Methods: C57Bl/6J mice underwent sciatic nerve ligation for the neuropathic pain model and were injected with 4% formalin into the hind paw for the inflammatory pain model. Each model was divided into four groups: vehicle, NK1 antagonist, CGRP antagonist, and combination treatment groups. The NK1 antagonist aprepitant (BIBN4096, 1 mg/kg) or the CGRP antagonist olcegepant (MK-0869, 10 mg/kg) was injected intraperitoneally. Mechanical allodynia, thermal hypersensitivity, and anxiety-related behaviors were assessed using the von Frey, hot plate, and elevated plus-maze tests. The flinching and licking responses were also evaluated after formalin injection. Results: Co-administration of aprepitant and olcegepant more significantly alleviated pain behaviors than administration of single agents or vehicle, increasing the mechanical threshold and improving the response latency. Anxiety-related behaviors were also markedly improved after dual treatment compared with either naive mice or the neuropathic pain model in the dual treatment group. Flinching frequency and licking response after formalin injection decreased significantly in the dual treatment group. Isobolographic analysis showed a meaningful additive effect between the two compounds. Conclusions: A combination pharmacological therapy comprised of multiple neuropeptide antagonists could be a more effective therapeutic strategy for alleviating neuropathic or inflammatory pain.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.137-142
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• 2000

Background: Systemic or intrathecal administration of gabapentin has been shown to reverse various pain states. However, until now, the effect of intracerebroventricular (ICV) gabapentin to noxious stimuli has not been reported. The authors' aim of this study was to determine the effect of ICV gabapentin on the inflammatory nociceptive model, formalin test, in rats. Methods: ICV catheters were implanted under halothane anesthesia. For the nociceptive test, $50{\mu}l$ of 5% formalin was subcutaneously injected into the hindpaw. The effect of ICV gabapentin, administered 10 min before formalin injection, were examined on flinching, mean arterial pressure and heart rate evoked by a injection of formalin. Results: Injection of formalin into the paw resulted in a biphasic flinching and cardiovascular response. ICV gabapentin produced a dose-dependent suppression of the flinching and mean arterial pressure response during phase 1. In contrast, in phase 2, ICV gabapentin did not attenuate the pain behavior. ICV gabapentin did not affect on the baseline mean arterial pressure and heart rate. Conclusions: ICV gbapentin was effective for the acute noxious stimulus but it had no effect on the facilitated states induced by tissue injury.

• The Korean Journal of Pain
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• v.30 no.3
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• pp.197-206
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• 2017

Background: Pain with neuropathic characteristics is generally more severe and associated with a lower quality of life compared to nociceptive pain (NcP). Short form of the Douleur Neuropathique en 4 Questions (S-DN4) is one of the most used and reliable screening questionnaires and is reported to have good diagnostic properties. This study was aimed to cross-culturally validate the Hindi version of the S-DN4 in patients with various chronic pain conditions. Methods: The S-DN4 is already translated into the Hindi language by Mapi Research Trust. This study assessed the psychometric properties of the Hindi version of the S-DN4 including internal consistency and test-retest reliability after 3 days' post-baseline assessment. Diagnostic performance was also assessed. Results: One hundred sixty patients with chronic pain, 80 each in the neuropathic pain (NeP) present and NeP absent groups, were recruited. Patients with NeP present reported significantly higher S-DN4 scores in comparison to patients in the NeP absent group (mean (SD), 4.7 (1.7) vs. 1.8 (1.6), P < 0.01). The S-DN4 was found to have an AUC of 0.88 with adequate internal consistency (Cronbach's ${\alpha}=0.80$) and a test-retest reliability (ICC = 0.92) with an optimal cut-off value of 3 (Youden's index = 0.66, sensitivity and specificity of 88.7% and 77.5%). The diagnostic concordance rate between clinician diagnosis and the S-DN4 questionnaire was 83.1% (kappa = 0.66). Conclusions: Overall, the Hindi version of the S-DN4 has good internal consistency and test-retest reliability along with good diagnostic accuracy.

• The Journal of Korean Physical Therapy
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• v.14 no.4
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• pp.20-27
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• 2002

A role for ATP in nociception and pain induction was proposed. ATP-gated P2X ion channel receptors are localized throughout the nervous system and have been identified on neurons which participate in conduction of nociceptive information from the periphery to central nervous system. We consider the role of ATP as a peripheral activator of nociceptive sensory neuron via ATP-gated ion channels.

• Journal of the Korean Academy of Clinical Electrophysiology
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• v.5 no.1
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• pp.73-83
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• 2007

This study aims to examine the effects on nociceptive neuron excitability by application of electroacupuncture in rat with inflammation. It used 20 rats for experiment, divided them into control group, electroacupuncture group (EA group), caused hyperalgesia by injecting ${\lambda}$-carrageenan into hindpaw and conducted treatment three times for experimental period. Change of NFR(reaction time, RMS) showed no significant differences among EA group showed significant differences compared to control group from 48 hours. This study showed that EA group had an effect on nociceptive neurone excitability. Therefore, it is considered that electroacupuncture for pain control will be very desirable.

• International Journal of Oral Biology
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• v.43 no.3
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• pp.147-153
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• 2018

The aim of the present study was to evaluate the central antinociceptive effects of eugenol after intraperitoneal administration. Experiments were carried out using male Sprague-Dawley rats. Subcutaneous injection of 5% formalin-induced nociceptive behavioral responses was used as the pain model. Subcutaneous injection of 5% formalin significantly produced nociceptive responses by increasing the licking time during nociceptive behavior. Subsequent intraperitoneal injection of 100 mg/kg of eugenol led to a significant decrease in the licking time. However, low dose of eugenol (50 mg/kg) did not affect the nociceptive behavioral responses produced by subcutaneous injection of formalin. Intrathecal injection of $30{\mu}g$ of naloxone, an opioid receptor antagonist, significantly blocked antinociceptive effects produced by intraperitoneal injection of eugenol. Neither intrathecal injection of methysergide ($30{\mu}g$), a serotonin receptor antagonist nor phentolamine ($30{\mu}g$), an ${\alpha}-adrenergic$ receptor antagonist influenced antinociceptive effects of eugenol, as compared to the vehicle treatment. These results suggest that central opioid pathway participates in mediating the antinociceptive effects of eugenol.

• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.259-265
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• 2017

This study aimed to investigate the analgesic effect of substance P (SP) in an animal model of neuropathic pain. An experimental model of neuropathic pain, the chronic constriction injury (CCI) model, was established using ICR mice. An intravenous (i.v.) injection of SP (1 nmole/kg) was administered to the mice to examine the analgesic effects of systemic SP on neuropathic pain. Behavioral testing and immunostaining was performed following treatment of the CCI model with SP. SP attenuated mechanical allodynia in a time-dependent manner, beginning at 1 h following administration, peaking at 1 day post-injection, and decaying by 3 days post-injection. The second injection of SP also increased the threshold of mechanical allodynia, with the effects peaking on day 1 and decaying by day 3. A reduction in phospho-ERK and glial fibrillary acidic protein (GFAP) accompanied the attenuation of mechanical allodynia. We have shown for the first time that i.v. administration of substance P attenuated mechanical allodynia in the maintenance phase of neuropathic pain using von Frey's test, and simultaneously reduced levels of phospho-ERK and GFAP, which are representative biochemical markers of neuropathic pain. Importantly, glial cells in the dorsal horn of the spinal cord (L4-L5) of SP-treated CCI mice, expressed the anti-inflammatory cytokine, IL-10, which was not seen in vehicle saline-treated mice. Thus, i.v. administration of substance P may be beneficial for improving the treatment of patients with neuropathic pain, since it decreases the activity of nociceptive factors and increases the expression of anti-nociceptive factors.

• Korean Journal of Pharmacognosy
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• v.51 no.3
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• pp.186-191
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• 2020

In this study, we evaluated the anti-nociceptive activities of Sorbus alnifolia. To investigate the anti-nociceptive properties of the methanolic extract of Sorbus alnifolia (MSA), we conducted several tests using various experimental mouse pain models. Herein, MSA significantly delayed the latency time and writhing motion in the hotplate test and acetic acid test, respectively. These result indicated that MSA has an ability to manage both peripheral and central nociception. We could further confirm the analgesic effects of MSA by performing formalin test. In combination test using naloxone, a non-selective opioid receptor antagonist, analgesic activity of MSA was partly antagonized by naloxone, but not completely, indicating that the MSA acts as a partial opioid receptor agonist. Out results suggest that the S. alnifolia may be possibly used as valuable anti-nociceptive agent.

• International Journal of Oral Biology
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• v.33 no.3
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• pp.97-103
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• 2008

The present study investigated the role of peripheral group I, II, and III metabotropic glutamate receptors (mGluRs) in mustard oil (MO)-induced nociceptive response in the masseter muscles of lightly anesthetized rats. Experiments were carried out on male Sprague-Dawley rats weighing 300-350 gm. After initial anesthesia with sodium pentobarbital (40 mg/kg, i.p.), one femoral vein was cannulated and connected to an infusion pump for intravenous infusion of sodium pentobarbital. The rate of infusion was adjusted to provide a constant level of anesthesia. MO (30 ${\mu}L$) was injected into the mid-region of the left masseter muscle via a 30-gauge needle over 10 seconds. After 30 mL injection of 5, 10, 15, or 20% MO into the masseter muscle, total number of hindpaw-shaking behavior was monitored. Intramuscular administration of MO significantly produced hindpawshaking behavior in a dose-dependent manner, as compared with the vehicle (mineral oil)-treated group. Intramuscular pretreatment with 10 or 100 ng DHPG, a group I mGluRs agonist, enhanced MO-induced hindpaw-shaking behavior, while APDC (20 or 200 ${\mu}g$), a group II mGluRs agonist, or L-AP4 (2 ${\mu}g$), a group III mGluRs agonist, significantly reduced MO-induced nociceptive behavior. The antinociception, produced by group II or III mGluRs agonists, was abolished by pretreatment with LY341495, a group II mGluRs antagonist, or CPPG, a group III mGluRs antagonist, res-pectively. Based on these observations, peripheral mGluRs differentially modulated MO-induced nociceptive behavior response in the craniofacial muscle pain and peripheral group II and III mGluRs agonists could be used in treatment of craniofacial muscle nociception.