• The Korean Journal of Physiology and Pharmacology
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• 제8권5호
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• pp.281-288
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• 2004

The present study was undertaken to confirm whether melittin, a major constituent of whole bee venom (WBV), had the ability to produce the same nociceptive responses as those induced by WBV. In the behavioral experiment, changes in mechanical threshold, flinching behaviors and paw thickness (edema) were measured after intraplantar (i.pl.) injection of WBV (0.1 mg & 0.3 mg/paw) and melittin (0.05 mg & 0.15 mg/paw), and intrathecal (i.t.) injection of melittin $(6{\mu}g)$. Also studied were the effects of i.p. (2 mg & 4 mg/kg), i.t. $(0.2{\mu}g\;&\;0.4{\mu}g)$ or i.pl. (0.3 mg) administration of morphine on melittin-induced pain responses. I.pl. injection of melittin at half the dosage of WBV strongly reduced mechanical threshold, and increased flinchings and paw thickness to a similar extent as those induced by WBV. Melittin- and WBV-induced flinchings and changes in mechanical threshold were dose- dependent and had a rapid onset. Paw thickness increased maximally about 1 hr after melittin and WBV treatment. Time-courses of nociceptive responses induced by melittin and WBV were very similar. Melittin-induced decreases in mechanical threshold and flinchings were suppressed by i.p., i.t. or i.pl. injection of morphine. I.t. administration of melittin $(6{\mu}g)$ reduced mechanical threshold of peripheral receptive field and induced flinching behaviors, but did not cause any increase in paw thickness. In the electrophysiological study, i.pl. injection of melittin increased discharge rates of dorsal horn neurons only with C fiber inputs from the peripheral receptive field, which were almost completely blocked by topical application of lidocaine to the sciatic nerve. These findings suggest that pain behaviors induced by WBV are mediated by melittin-induced activation of C afferent fiber, that the melittin-induced pain model is a very useful model for the study of pain, and that melittin-induced nociceptive responses are sensitive to the widely used analgesics, morphine.

• Biomolecules & Therapeutics
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• 제24권5호
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• pp.489-494
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• 2016

Neuropathic pain (NPP) is the main culprit among chronic pains affecting the normal life of patients. Procaine is a frequently-used local anesthesia with multiple efficacies in various diseases. However, its role in modulating NPP has not been reported yet. This study aims at uncovering the role of procaine in NPP. Rats were pretreated with procaine by intrathecal injection. Then NPP rat model was induced by sciatic nerve chronic compression injury (CCI) and behavior tests were performed to analyze the pain behaviors upon mechanical, thermal and cold stimulations. Spinal expression of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) was detected by qRT-PCR and western blot. JAK2 was also overexpressed in procaine treated model rats for behavior tests. Results showed that procaine pretreatment improved the pain behaviors of model rats upon mechanical, thermal and cold stimulations, with the best effect occurring on the $15^{th}$ day post model construction (p<0.05). Procaine also inhibited JAK2 and STAT3 expression in both mRNA (p<0.05) and protein levels. Overexpression of JAK2 increased STAT3 level and reversed the improvement effects of procaine in pain behaviors (p<0.01). These findings indicate that procaine is capable of attenuating NPP, suggesting procaine is a potential therapeutic strategy for treating NPP. Its role may be associated with the inhibition on JAK2/STAT3 signaling.

• 대한약침학회지
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• 제17권1호
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• pp.74-79
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• 2014

Objectives: This study was conducted to clarify the analgesic effect of toad cake and toad-cake-containing herbal drugs. Methods: We counted the writhing response of mice after the intraperitoneal administration of acetic acid as a nociceptive pain model and the withdrawal response after the plantar surface stimulation of the hind paw induced by partial sciatic nerve ligation of the mice as a neuropathic pain model to investigate the analgesic effect of toad cake and toad-cake-containing herbal drugs. A co-treatment study with serotonin biosynthesis inhibitory drug 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA), the catecholamine biosynthesis inhibitory drug ${\alpha}$-methyl-DL-tyrosine methyl ester hydrochloride (AMPT) or the opioid receptor antagonist naloxone hydrochloride was also conducted. Results: Analgesic effects in a mouse model of nociceptive pain and neuropathic pain were shown by oral administration of toad cake and toad-cake-containing herbal drugs. The effects of toad cake and toad-cake-containing herbal drugs disappeared upon co-treatment with PCPA, but not with AMPT or naloxone in the nociceptive pain model; the analgesic effect of toad-cake-containing herbal drugs also disappeared upon co-treatment with PCPA in the neuropathic pain model. Conclusion: Toad cake and toad-cake-containing herbal drugs have potential for the treatments of nociceptive pain and of neuropathic pain, such as post-herpetic neuralgia, trigeminal neuralgia, diabetic neuralgia, and postoperative or posttraumatic pain, by activation of the central serotonin nervous system.

• 동의생리병리학회지
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• 제23권3호
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• pp.678-684
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• 2009

It was reported that Dipsaci Radix has decrease pain effect on the Complex Region Pain Syndrome(CRPS). the CRPS was induced by unilateral loose occlusion in 4 part of the sciatic nerve of the rats. For the fingding significantly change on CRPS rats were divided into 4 different experimental groups. and each groups were induced CRPS. Experimental group I (control group; n=15), experimental group II (100 mg/kg Dipsaci Radix dieted rats; n=15), experimental group III (300 mg/kg Dipsaci Radix dieted rats; n=15), and experimental group IV(500 mg/kg Dipsaci Radix dieted rats; n=15). The study of Dipsaci Radix concentration was that foot withdrawal threshold to the thermal stimuli(Hot plate test), foot withdrawal threshold to the mechanical stimuli(von Frey's filament) and immunohistochemistry staining that were substance P. Hot plate test and von Frey Filament were increase in experimental group II, III, IV than group I, especially group III was most significantly change than group II and IV in post-hoc(Duncan's multiple range). and In immunohistochemistry observation; group I showed increase in the group II, III, IV. especially group III had the minimal level of the substance P expression while the experimental group II, III. These results suggested that the Dipsaci Radix dieted made the decrease of pain in CRPS.

• 한국임상수의학회지
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• 제26권6호
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• pp.632-636
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• 2009

회음부 팽대 병력을 보이는 세 마리 개가 건국대학교 부속 동물병원과 한강 동물병원에 내원하였다. 회음부 팽대 외에 다른 증상이 없었으며 신체 검사에서 두 마리는 환납성 한 마리는 비 환납성임을 확인 하였다. 일반 방사선 사진에서 골반강 또는 복강 내 장기가 탈장 낭 내에 없음을 확인하였다. 회음 탈장의 교정을 위해 내폐쇄근 변위 탈장 봉합술 실시 하였다. 한 마리에서 수술 후 지방을 함유하고 있는 대측 탈장이 확인되었다. 수술 후 정기 점진은 수의사의 신체 검사 혹은 보호자와의 전화 통화를 통해 실시 되었으며 세 마리 모두에서 수술과 관련한 좌골 신경 손상, 직장 탈출, 수술 부위 열개, 회음 탈장 재발과 같은 합병 증상이 없음을 확인하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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• pp.253-258
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• 2008

Somatostatin (SOM) is a widely distributed peptide in the central nervous system and exerts a variety of hormonal and neural actions. Although SOM is assumed to play an important role in spinal nociceptive processing, its exact function remains unclear. In fact, earlier pharmacological studies have provided results that support either a facilitatory or inhibitory role for SOM in nociception. In the current study, the effects of SOM were investigated using anesthetized cats. Specifically, the responses of rostrally projecting spinal dorsal horn neurons (RPSDH neurons) to different kinds of noxious stimuli (i.e., heat, mechanical and cold stimuli) and to the $A{\delta}$ -and C-fiber activation of the sciatic nerve were studied. Iontophoretically applied SOM suppressed the responses of RPSDH neurons to noxious heat and mechanical stimuli as well as to C-fiber activation. Conversely, it enhanced these responses to noxious cold stimulus and $A{\delta}$-fiber activation. In addition, SOM suppressed glutamate-evoked activities of RPSDH neurons. The effects of SOM were blocked by the SOM receptor antagonist cyclo-SOM. These findings suggest that SOM has a dual effect on the activities of RPSDH neurons; that is, facilitation and inhibition, depending on the modality of pain signaled through them and its action site.

• The Journal of Korean Physical Therapy
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• 제14권2호
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• pp.145-152
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• 2002

고압맥동전류가 탈신경근의 형태에 미치는 영향을 알아보기 위하여 조직화학적 방법과 투과전자현미경적 관찰을 하였다. 웅성 흰쥐를 정상군, 탈신경군으로 각각 8마리씩 나누어 2주와 4주 후에 희생시켜 실험한 결과 다음과 같은 결과를 얻었다. 1. 조직화학적으로 형태를 관찰 한 결과 대조 1주군부터 근속과 근섬유사이에 염증세포가 관찰되고 핵이 근섬유속에 위치하는 것도 자주 관찰되었다. 2. 대조군도 비슷한 양상을 보였으나 4주군은 근괴사와 염증세포가 더욱 증가하였다. 3. 당원 1주군에서 실험군, 대조군 모두 정상근과 비슷한 양상을 보이나 4주군에서는 섬유를 구별할 수 없는 형태로 관찰되었다. 4. NADH-TR반응에서 적색섬유가 2주군에서 약간 증가하였고 그 후로는 구별이 불가능하였다. 5. 미세구조적으로 양쪽군 모두 근섬유가 굽어있고 mitochondria의 파괴로 인한 공포가 많이 관찰되었으나 전기자극 2주군에서는 일부에서 mitochondria증가를 관찰 하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제25권3호
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• pp.217-225
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• 2021

Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-κB signaling pathway-associated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-κB signaling pathway-related proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.

• The Korean Journal of Pain
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• 제35권2호
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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.

• Journal of Ginseng Research
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• 제48권1호
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• pp.52-58
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• 2024

Background: Skeletal muscle denervation leads to motor neuron degeneration, which in turn reduces muscle fiber volumes. Recent studies have revealed that apoptosis plays a role in regulating denervation-associated pathologic muscle wasting. Korean red ginseng (KRG) has various biological activities and is currently widely consumed as a medicinal product worldwide. Among them, ginseng has protective effects against muscle atrophy in in vivo and in vitro. However, the effects of KRG on denervation-induced muscle damage have not been fully elucidated. Methods: We induced skeletal muscle atrophy in mice by dissecting the sciatic nerves, administered KRG, and then analyzed the muscles. KRG was administered to the mice once daily for 3 weeks at 100 and 400 mg/kg/day doses after operation. Results: KRG treatment significantly increased skeletal muscle weight and tibialis anterior (TA) muscle fiber volume in injured areas and reduced histological alterations in TA muscle. In addition, KRG treatment reduced denervation-induced apoptotic changes in TA muscle. KRG attenuated p53/Bax/cytochrome c/Caspase 3 signaling induced by nerve injury in a dose-dependent manner. Also, KRG decreases protein kinase B/mammalian target of rapamycin pathway, reducing restorative myogenesis. Conclusion: Thus, KRG has potential protective role against denervation-induced muscle atrophy. The effect of KRG treatment was accompanied by reduced levels of mitochondria-associated apoptosis.