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Prof. Woojin Kim
Kyung Hee University, Seoul, Republic of Korea

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0 Acupuncture
0 Neuropathic Pain
0 Oxaliplatin
0 herbal medicines
0 Chemotherapy-induced side effects

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Oxaliplatin
Neuropathic Pain
Bee Venom
Acupuncture

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Journal article
Published: 16 August 2021 in International Journal of Molecular Sciences
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Oxaliplatin, a well-known chemotherapeutic agent, can induce severe neuropathic pain, which can seriously decrease the quality of life of patients. JI017 is an herb mixture composed of Aconitum carmichaelii, Angelica gigas, and Zingiber officinale. Its anti-tumor effect has been reported; however, the efficacy of JI017 against oxaliplatin-induced allodynia has never been explored. Single oxaliplatin injection [6 mg/kg, intraperitoneal, (i.p.)] induced both cold and mechanical allodynia, and oral administration of JI017 (500 mg/kg) alleviated cold but not mechanical allodynia in mice. Real-time polymerase chain reaction (PCR) analysis demonstrated that the upregulation of mRNA of spinal transient receptor potential vanilloid 1 (TRPV1) and astrocytes following oxaliplatin injection was downregulated after JI017 treatment. Moreover, TRPV1 expression and the activation of astrocytes were intensely increased in the superficial area of the spinal dorsal horn after oxaliplatin treatment, whereas JI017 suppressed both. The administration of TRPV1 antagonist [capsazepine, intrathecal (i.t.), 10 μg] attenuated the activation of astrocytes in the dorsal horn, demonstrating that the functions of spinal TRPV1 and astrocytes are closely related in oxaliplatin-induced neuropathic pain. Altogether, these results suggest that JI017 may be a potent candidate for the management of oxaliplatin-induced neuropathy as it decreases pain, spinal TRPV1, and astrocyte activation.

ACS Style

Ji Hwan Lee; Hyunseung Ji; Seong-Gyu Ko; Woojin Kim. JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice. International Journal of Molecular Sciences 2021, 22, 8811 .

AMA Style

Ji Hwan Lee, Hyunseung Ji, Seong-Gyu Ko, Woojin Kim. JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice. International Journal of Molecular Sciences. 2021; 22 (16):8811.

Chicago/Turabian Style

Ji Hwan Lee; Hyunseung Ji; Seong-Gyu Ko; Woojin Kim. 2021. "JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice." International Journal of Molecular Sciences 22, no. 16: 8811.

Review
Published: 09 August 2021 in International Journal of Molecular Sciences
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Diabetic neuropathy, a major complication of diabetes mellitus, refers to a collection of clinically diverse disorders affecting the nervous system that may present with pain. Although the number of patients suffering from severe neuropathy is increasing, no optimal treatment method has been developed yet. Acupuncture is well known for its ability to reduce various kinds of pain, and a number of studies have also reported its effect on diabetes mellitus; however, its effect and underlying mechanism against diabetic neuropathy are not yet clearly understood. In this review, ten and five studies performed in humans and animals, respectively, were analyzed. All studies reported that acupuncture significantly relieved diabetic neuropathy. ST36, BL13, BL20, SP6, and SP9 were the most widely used acupoints. Five studies used electro-acupuncture, whereas other studies used manual acupuncture. Furthermore, the effect of acupuncture was shown to be mediated through the various molecules present in the peripheral nerves and spinal cord, such as P65, GPR78, and TRPV1. Five studies reported side effects, such as swelling, numbness, and nausea, but none were reported to be serious. Based on these results, we suggest that acupuncture should be considered as a treatment option for diabetic neuropathy.

ACS Style

Eunwoo Cho; Woojin Kim. Effect of Acupuncture on Diabetic Neuropathy: A Narrative Review. International Journal of Molecular Sciences 2021, 22, 8575 .

AMA Style

Eunwoo Cho, Woojin Kim. Effect of Acupuncture on Diabetic Neuropathy: A Narrative Review. International Journal of Molecular Sciences. 2021; 22 (16):8575.

Chicago/Turabian Style

Eunwoo Cho; Woojin Kim. 2021. "Effect of Acupuncture on Diabetic Neuropathy: A Narrative Review." International Journal of Molecular Sciences 22, no. 16: 8575.

Review
Published: 06 August 2021 in Biomedicines
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Oxaliplatin is a chemotherapeutic agent widely used against colorectal and breast cancers; however, it can also induce peripheral neuropathy that can rapidly occur even after a single infusion in up to 80–90% of treated patients. Numerous efforts have been made to understand the underlying mechanism and find an effective therapeutic agent that could diminish pain without damaging its anti-tumor effect. However, its mechanism is not yet clearly understood. The serotonergic system, as part of the descending pain inhibitory system, has been reported to be involved in different types of pain. The malfunction of serotonin (5-hydroxytryptamine; 5-HT) or its receptors has been associated with the development and maintenance of pain. However, its role in oxaliplatin-induced neuropathy has not been clearly elucidated. In this review, 16 in vivo studies focused on the role of the serotonergic system in oxaliplatin-induced neuropathic pain were analyzed. Five studies analyzed the involvement of 5-HT, while fourteen studies observed the role of its receptors in oxaliplatin-induced allodynia. The results show that 5-HT is not involved in the development of oxaliplatin-induced allodynia, but increasing the activity of the 5-HT1A, 5-HT2A, and 5-HT3 receptors and decreasing the action of 5-HT2C and 5-HT6 receptors may help inhibit pain.

ACS Style

Ji Lee; Woojin Kim. Involvement of Serotonergic System in Oxaliplatin-Induced Neuropathic Pain. Biomedicines 2021, 9, 970 .

AMA Style

Ji Lee, Woojin Kim. Involvement of Serotonergic System in Oxaliplatin-Induced Neuropathic Pain. Biomedicines. 2021; 9 (8):970.

Chicago/Turabian Style

Ji Lee; Woojin Kim. 2021. "Involvement of Serotonergic System in Oxaliplatin-Induced Neuropathic Pain." Biomedicines 9, no. 8: 970.

Review
Published: 30 July 2021 in Processes
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Cancer incidence and mortality rate are growing worldwide. The effectiveness of cancer therapy depends on the degree of cancer development. Anticancer prevention, screening tests, detection of precancerous conditions or cancers at an early stage of development help to prevent the development of cancer, and in the event of cancer development, they provide the best chance for a full recovery. However, in most cases of advanced cancer, there is no method that can fully cure this disease. Recently, natural products have gained more attention in cancer therapy. Panax ginseng (PG), one of the most popular natural products, is reported to have a wide range of pharmacological activities in cancer. Therefore, the anti-cancer effects and mechanisms of PG and its metabolites (compound K, Ginsenoside Rh1, Rh2, Rh3 and F1) in five major cancers (lung cancer, breast cancer, colon cancer, prostate cancer and stomach cancer) are reviewed in this study. It is confirmed that PG and its metabolites regulated apoptosis, epithelial mesenchymal transition (EMT), angiogenesis, cell cycle arrest and multidrug resistance (MDR) in vitro and in vivo cancer models. In particular, ginsenoside Rh2 showed anticancer effects in all five major cancers. This review could improve the understanding of anticancer mechanisms of PG and its metabolites against major five cancers. Further clinical studies are needed for development anti-cancer drugs using PG and its metabolites.

ACS Style

Sejin Kim; Nayeon Kim; Jayeon Jeong; Soojin Lee; Woojin Kim; Seong-Gyu Ko; Bonglee Kim. Anti-Cancer Effect of Panax Ginseng and Its Metabolites: From Traditional Medicine to Modern Drug Discovery. Processes 2021, 9, 1344 .

AMA Style

Sejin Kim, Nayeon Kim, Jayeon Jeong, Soojin Lee, Woojin Kim, Seong-Gyu Ko, Bonglee Kim. Anti-Cancer Effect of Panax Ginseng and Its Metabolites: From Traditional Medicine to Modern Drug Discovery. Processes. 2021; 9 (8):1344.

Chicago/Turabian Style

Sejin Kim; Nayeon Kim; Jayeon Jeong; Soojin Lee; Woojin Kim; Seong-Gyu Ko; Bonglee Kim. 2021. "Anti-Cancer Effect of Panax Ginseng and Its Metabolites: From Traditional Medicine to Modern Drug Discovery." Processes 9, no. 8: 1344.

Journal article
Published: 20 March 2021 in International Journal of Molecular Sciences
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Cachexia causes high mortality, low quality of life, and rapid weight loss in cancer patients. Sarcopenia, a condition characterized by the loss of muscle, is generally present in cachexia and is associated with inflammation. M2 macrophages, also known as an anti-inflammatory or alternatively activated macrophages, have been shown to play a role in muscle repair. Magnoliae Cortex (M.C) is a widely used medicinal herb in East Asia reported to have a broad range of anti-inflammatory activities; however, the effects of M.C on sarcopenia and on M2 macrophage polarization have to date not been studied. This study was designed to investigate whether the oral administration of M.C could decrease cisplatin-induced sarcopenia by modulating M2 macrophage polarization in mice. C57BL/6 mice were injected intraperitoneally with cisplatin (2.5 mg/kg) to mimic chemotherapy-induced sarcopenia. M.C extract (50, 100, and 200 mg/kg) was administered orally every 3 days (for a total of 12 times). M.C (100 and 200 mg/kg) significantly alleviated the cisplatin-induced loss of body mass, skeletal muscle weight, and grip strength. In addition, M.C increased the expression of M2 macrophage markers, such as MRC1, CD163, TGF-β, and Arg-1, and decreased the expression of M1-specific markers, including NOS2 and TNF-α, in skeletal muscle. Furthermore, the levels of like growth factor-1(IGF-1), as well as the number of M2a and M2c macrophages, significantly increased in skeletal muscle after M.C administration. M.C did not interfere with the anticancer effect of cisplatin in colon cancer. Our results demonstrated that M.C can alleviate cisplatin-induced sarcopenia by increasing the number of M2 macrophages. Therefore, our findings suggest that M.C could be used as an effective therapeutic agent to reverse or prevent cisplatin-induced sarcopenia.

ACS Style

Minwoo Hong; Ik-Hwan Han; Ilseob Choi; Nari Cha; Woojin Kim; Sun Kim; Hyunsu Bae. Magnoliae Cortex Alleviates Muscle Wasting by Modulating M2 Macrophages in a Cisplatin-Induced Sarcopenia Mouse Model. International Journal of Molecular Sciences 2021, 22, 3188 .

AMA Style

Minwoo Hong, Ik-Hwan Han, Ilseob Choi, Nari Cha, Woojin Kim, Sun Kim, Hyunsu Bae. Magnoliae Cortex Alleviates Muscle Wasting by Modulating M2 Macrophages in a Cisplatin-Induced Sarcopenia Mouse Model. International Journal of Molecular Sciences. 2021; 22 (6):3188.

Chicago/Turabian Style

Minwoo Hong; Ik-Hwan Han; Ilseob Choi; Nari Cha; Woojin Kim; Sun Kim; Hyunsu Bae. 2021. "Magnoliae Cortex Alleviates Muscle Wasting by Modulating M2 Macrophages in a Cisplatin-Induced Sarcopenia Mouse Model." International Journal of Molecular Sciences 22, no. 6: 3188.

Editorial
Published: 07 March 2021 in Toxins
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Bee venom, which is a complex substance produced by Apis mellifera, is widely used to treat various diseases, such as pain

ACS Style

Woojin Kim. Bee Venom and Its Sub-Components: Characterization, Pharmacology, and Therapeutics. Toxins 2021, 13, 191 .

AMA Style

Woojin Kim. Bee Venom and Its Sub-Components: Characterization, Pharmacology, and Therapeutics. Toxins. 2021; 13 (3):191.

Chicago/Turabian Style

Woojin Kim. 2021. "Bee Venom and Its Sub-Components: Characterization, Pharmacology, and Therapeutics." Toxins 13, no. 3: 191.

Journal article
Published: 21 January 2021 in Molecules
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Oxaliplatin is a platinum derivative chemotherapeutic drug widely used against cancers, but even a single treatment can induce a severe allodynia that requires treatment interruption and dose diminution. The rhizome of Zingiber officinale roscoe (Z. officinale, ginger), has been widely used in traditional medicine to treat various diseases causing pain; however, its effect against oxaliplatin-induced neuropathic pain has never been assessed. In mice, a single oxaliplatin (6 mg/kg, i.p.) treatment induced significant cold and mechanical allodynia. Cold and mechanical allodynia were assessed by acetone drop and von Frey filament tests, respectively. Water extracts of Z. officinale (100, 300, and 500 mg/kg, p.o.) significantly attenuated both cold and mechanical allodynia induced by oxaliplatin. Intrathecal pre-treatment with the antagonist 5-HT1A (NAN-190, i.t., 1 μg), but not with the antagonist 5-HT2A (ketanserin, i.t., 1 μg), significantly blocked the analgesic effect of Z. officinale against both cold and mechanical allodynia. However, 5-HT3 antagonist (MDL-72222, i.t., 15 μg) administration only blocked the anti-allodynic effect of Z. officinale against cold allodynia. Real-time PCR analysis demonstrated that Z. officinale significantly increased the mRNA expression of the spinal 5-HT1A receptor that was downregulated after oxaliplatin injection. These results suggest that Z. officinale may be a viable treatment option for oxaliplatin-induced neuropathic pain.

ACS Style

Ji Lee; Daeun Min; Donghun Lee; Woojin Kim. Zingiber officinale Roscoe Rhizomes Attenuate Oxaliplatin-Induced Neuropathic Pain in Mice. Molecules 2021, 26, 548 .

AMA Style

Ji Lee, Daeun Min, Donghun Lee, Woojin Kim. Zingiber officinale Roscoe Rhizomes Attenuate Oxaliplatin-Induced Neuropathic Pain in Mice. Molecules. 2021; 26 (3):548.

Chicago/Turabian Style

Ji Lee; Daeun Min; Donghun Lee; Woojin Kim. 2021. "Zingiber officinale Roscoe Rhizomes Attenuate Oxaliplatin-Induced Neuropathic Pain in Mice." Molecules 26, no. 3: 548.

Journal article
Published: 24 November 2020 in Toxins
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Oxaliplatin is a third-generation platinum-based chemotherapeutic drug widely used in colorectal cancer treatment. Although potent against this tumor, it can induce cold and mechanical allodynia even after a single injection. The currently used drugs to attenuate this allodynia can also cause unwanted effects, which limit their use. Bee venom acupuncture (BVA) is widely used in Korean medicine to treat pain. Although the effect of BVA on oxaliplatin-induced neuropathic pain has been addressed in many studies, its action on dorsal root ganglia (DRG) neurons has never been investigated. A single oxaliplatin injection (6 mg/kg, intraperitoneally) induced cold and mechanical allodynia, and BVA (0.1 and 1 mg/kg, subcutaneous, ST36) dose-dependently decreased allodynia in rats. On acutely dissociated lumbar 4–6 DRG neurons, 10 min application of oxaliplatin (100 μM) shifted the voltage-dependence of sodium conductance toward negative membrane potentials in A- but not C-fibers. The resting membrane potential remained unchanged, but the action potential threshold decreased significantly compared to that of the control (p < 0.05). However, 0.1 μg/mL of BVA administration increased the lowered action potential threshold. In conclusion, these results suggest that BVA may attenuate oxaliplatin-induced neuropathic pain by altering the action potential threshold in A-fiber DRG neurons.

ACS Style

Ji Hwan Lee; Juan Gang; Eunhee Yang; Woojin Kim; Young-Ho Jin. Bee Venom Acupuncture Attenuates Oxaliplatin-Induced Neuropathic Pain by Modulating Action Potential Threshold in A-Fiber Dorsal Root Ganglia Neurons. Toxins 2020, 12, 737 .

AMA Style

Ji Hwan Lee, Juan Gang, Eunhee Yang, Woojin Kim, Young-Ho Jin. Bee Venom Acupuncture Attenuates Oxaliplatin-Induced Neuropathic Pain by Modulating Action Potential Threshold in A-Fiber Dorsal Root Ganglia Neurons. Toxins. 2020; 12 (12):737.

Chicago/Turabian Style

Ji Hwan Lee; Juan Gang; Eunhee Yang; Woojin Kim; Young-Ho Jin. 2020. "Bee Venom Acupuncture Attenuates Oxaliplatin-Induced Neuropathic Pain by Modulating Action Potential Threshold in A-Fiber Dorsal Root Ganglia Neurons." Toxins 12, no. 12: 737.

Review
Published: 02 September 2020 in Biomedicines
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Oxaliplatin is a third-generation platinum-based chemotherapeutic drug. Although its efficacy against colorectal cancer is well known, peripheral neuropathy that develops during and after infusion of the agents could decrease the quality of life of the patients. Various pathways have been reported to be the cause of the oxaliplatin-induced paresthesia and dysesthesia; however, its mechanism of action has not been fully understood yet. In recent years, researchers have investigated the function of glia in pain, and demonstrated that glia in the peripheral and central nervous system could play a critical role in the development and maintenance of neuropathic pain. These results suggest that targeting the glia may be an effective therapeutic option. In the past ten years, 20 more papers focused on the role of glia in oxaliplatin-induced thermal and mechanical hypersensitivity. However, to date no review has been written to summarize and discuss their results. Thus, in this study, by reviewing 23 studies that conducted in vivo experiments in rodents, the change of satellite glial cells, astrocytes, and microglia activation in the dorsal root ganglia, spinal cord, and the brain of oxaliplatin-induced neuropathic pain animals is discussed.

ACS Style

Ji Hwan Lee; Woojin Kim. The Role of Satellite Glial Cells, Astrocytes, and Microglia in Oxaliplatin-Induced Neuropathic Pain. Biomedicines 2020, 8, 324 .

AMA Style

Ji Hwan Lee, Woojin Kim. The Role of Satellite Glial Cells, Astrocytes, and Microglia in Oxaliplatin-Induced Neuropathic Pain. Biomedicines. 2020; 8 (9):324.

Chicago/Turabian Style

Ji Hwan Lee; Woojin Kim. 2020. "The Role of Satellite Glial Cells, Astrocytes, and Microglia in Oxaliplatin-Induced Neuropathic Pain." Biomedicines 8, no. 9: 324.

Review
Published: 09 June 2020 in Processes
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Oxaliplatin is a chemotherapeutic drug widely used to treat various types of tumors. However, it can induce a serious peripheral neuropathy characterized by cold and mechanical allodynia that can even disrupt the treatment schedule. Since the approval of the agent, many laboratories, including ours, have focused their research on finding a drug or method to decrease this side effect. However, to date no drug that can effectively reduce the pain without causing any adverse events has been developed, and the mechanism of the action of oxaliplatin is not clearly understood. On the dorsal root ganglia (DRG) sensory neurons, oxaliplatin is reported to modify their functions, such as the propagation of the action potential and induction of neuropathic pain. Voltage-gated sodium channels in the DRG neurons are important, as they play a major role in the excitability of the cell by initiating the action potential. Thus, in this small review, eight studies that investigated the effect of oxaliplatin on sodium channels of peripheral neurons have been included. Its effects on the duration of the action potential, peak of the sodium current, voltage–response relationship, inactivation current, and sensitivity to tetrodotoxin (TTX) are discussed.

ACS Style

Woojin Kim. Effect of Oxaliplatin on Voltage-Gated Sodium Channels in Peripheral Neuropathic Pain. Processes 2020, 8, 680 .

AMA Style

Woojin Kim. Effect of Oxaliplatin on Voltage-Gated Sodium Channels in Peripheral Neuropathic Pain. Processes. 2020; 8 (6):680.

Chicago/Turabian Style

Woojin Kim. 2020. "Effect of Oxaliplatin on Voltage-Gated Sodium Channels in Peripheral Neuropathic Pain." Processes 8, no. 6: 680.

Journal article
Published: 08 July 2019 in Toxins
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Oxaliplatin is a chemotherapeutic agent used for metastatic colon and other advanced cancers. Most common side effect of oxaliplatin is peripheral neuropathy, manifested in mechanical and cold allodynia. Although the analgesic effect of bee venom has been proven to be effective against oxaliplatin-induced peripheral neuropathy, the effect of its major component; melittin has not been studied yet. Thus, in this study, we investigated whether melittin has an analgesic effect on oxaliplatin-induced allodynia. Intraperitoneal single injection of oxaliplatin (6 mg/kg) induced mechanical and cold allodynia, resulting in increased withdrawal behavior in response to von Frey filaments and acetone drop on hind paw. Subcutaneous melittin injection on acupoint ST36 (0.5 mg/kg) alleviated oxaliplatin-induced mechanical and cold allodynia. In electrophysiological study, using spinal in vivo extracellular recording, it was shown that oxaliplatin-induced hyperexcitation of spinal wide dynamic range neurons in response to peripheral stimuli, and melittin administration inhibited this neuronal activity. In behavioral assessment, analgesic effect of melittin was blocked by intrathecal α1- and α2- adrenergic receptor antagonists administration. Based on these results, we suggest that melittin could be used as an analgesic on oxaliplatin-induced peripheral neuropathy, and that its effect is mediated by activating the spinal α1- and α2-adrenergic receptors.

ACS Style

Seunghwan Choi; Hyeon Kyeong Chae; Ho Heo; Dae-Hyun Hahm; Woojin Kim; Sun Kwang Kim. Analgesic Effect of Melittin on Oxaliplatin-Induced Peripheral Neuropathy in Rats. Toxins 2019, 11, 396 .

AMA Style

Seunghwan Choi, Hyeon Kyeong Chae, Ho Heo, Dae-Hyun Hahm, Woojin Kim, Sun Kwang Kim. Analgesic Effect of Melittin on Oxaliplatin-Induced Peripheral Neuropathy in Rats. Toxins. 2019; 11 (7):396.

Chicago/Turabian Style

Seunghwan Choi; Hyeon Kyeong Chae; Ho Heo; Dae-Hyun Hahm; Woojin Kim; Sun Kwang Kim. 2019. "Analgesic Effect of Melittin on Oxaliplatin-Induced Peripheral Neuropathy in Rats." Toxins 11, no. 7: 396.

Journal article
Published: 03 April 2019 in International Journal of Molecular Sciences
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The analgesic effect of venlafaxine (VLX), which is a selective serotonin and noradrenaline reuptake inhibitor (SNRI), has been observed on oxaliplatin-induced neuropathic pain in mice. Significant allodynia was shown after oxaliplatin treatment (6 mg/kg, i.p.); acetone and von Frey hair tests were used to assess cold and mechanical allodynia, respectively. Intraperitoneal administration of VLX at 40 and 60 mg/kg, but not 10 mg/kg, significantly alleviated these allodynia. Noradrenaline depletion by pretreatment of N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 50 mg/kg, i.p.) blocked the relieving effect of VLX (40 mg/kg, i.p.) on cold and mechanical allodynia. However, serotonin depletion by three consecutive pretreatments of para-chlorophenylalanine (PCPA, 150 mg/kg/day, i.p.) only blocked the effect of VLX on mechanical allodynia. In cold allodynia, the α2-adrenergic antagonist idazoxan (10 μg, i.t.), but not the α1-adrenergic antagonist prazosin (10 μg, i.t.), abolished VLX-induced analgesia. Furthermore, idazoxan and 5-HT3 receptor antagonist bemesetron (MDL-72222, 15 μg, i.t.), but not prazosin or mixed 5-HT1, 2 receptor antagonist methysergide (10 μg, i.t.), abolished VLX-induced analgesia in mechanical allodynia. In conclusion, 40 mg/kg of VLX treatment has a potent relieving effect against oxaliplatin-induced neuropathic pain, and α2-adrenergic receptor, and both α2-adrenergic and 5-HT3 receptors are involved in this effect of VLX on cold and mechanical allodynia, respectively.

ACS Style

Daxian Li; Ji Hwan Lee; Chang Won Choi; Jaihwan Kim; Sun Kwang Kim; Woojin Kim. The Analgesic Effect of Venlafaxine and Its Mechanism on Oxaliplatin-Induced Neuropathic Pain in Mice. International Journal of Molecular Sciences 2019, 20, 1652 .

AMA Style

Daxian Li, Ji Hwan Lee, Chang Won Choi, Jaihwan Kim, Sun Kwang Kim, Woojin Kim. The Analgesic Effect of Venlafaxine and Its Mechanism on Oxaliplatin-Induced Neuropathic Pain in Mice. International Journal of Molecular Sciences. 2019; 20 (7):1652.

Chicago/Turabian Style

Daxian Li; Ji Hwan Lee; Chang Won Choi; Jaihwan Kim; Sun Kwang Kim; Woojin Kim. 2019. "The Analgesic Effect of Venlafaxine and Its Mechanism on Oxaliplatin-Induced Neuropathic Pain in Mice." International Journal of Molecular Sciences 20, no. 7: 1652.

Journal article
Published: 19 February 2019 in Nutrients
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A chemotherapy drug, oxaliplatin, induces cold and mechanical hypersensitivity, but effective treatments for this neuropathic pain without side effects are still lacking. We previously showed that Cinnamomi Cortex suppresses oxaliplatin-induced pain behaviors in rats. However, it remains unknown which phytochemical of Cinnamomi Cortex plays a key role in that analgesic action. Thus, here we investigated whether and how cinnamic acid or cinnamaldehyde, major components of Cinnamomi Cortex, alleviates cold and mechanical allodynia induced by a single oxaliplatin injection (6 mg/kg, i.p.) in rats. Using an acetone test and the von Frey test for measuring cold and mechanical allodynia, respectively, we found that administration of cinnamic acid, but not cinnamaldehyde, at doses of 10, 20 and 40 mg/kg (i.p.) significantly attenuates the allodynic behaviors in oxaliplatin-injected rats with the strongest effect being observed at 20 mg/kg. Our in vivo extracellular recordings also showed that cinnamic acid (20 mg/kg, i.p.) inhibits the increased activities of spinal wide dynamic range neurons in response to cutaneous mechanical and cold stimuli following the oxaliplatin injection. These results indicate that cinnamic acid has an effective analgesic action against oxaliplatin-induced neuropathic pain through inhibiting spinal pain transmission, suggesting its crucial role in mediating the effect of Cinnamomi Cortex.

ACS Style

Hyeon Kyeong Chae; Woojin Kim; Sun Kwang Kim. Phytochemicals of Cinnamomi Cortex: Cinnamic Acid, but not Cinnamaldehyde, Attenuates Oxaliplatin-Induced Cold and Mechanical Hypersensitivity in Rats. Nutrients 2019, 11, 432 .

AMA Style

Hyeon Kyeong Chae, Woojin Kim, Sun Kwang Kim. Phytochemicals of Cinnamomi Cortex: Cinnamic Acid, but not Cinnamaldehyde, Attenuates Oxaliplatin-Induced Cold and Mechanical Hypersensitivity in Rats. Nutrients. 2019; 11 (2):432.

Chicago/Turabian Style

Hyeon Kyeong Chae; Woojin Kim; Sun Kwang Kim. 2019. "Phytochemicals of Cinnamomi Cortex: Cinnamic Acid, but not Cinnamaldehyde, Attenuates Oxaliplatin-Induced Cold and Mechanical Hypersensitivity in Rats." Nutrients 11, no. 2: 432.

Editorial
Published: 10 June 2018 in Evidence-Based Complementary and Alternative Medicine
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ACS Style

Gihyun Lee; Wonnam Kim; Woojin Kim; Hanbing Li. Modernization of Traditional Oriental Medicine: New Dosage Forms and Medical Instruments. Evidence-Based Complementary and Alternative Medicine 2018, 2018, 1 -1.

AMA Style

Gihyun Lee, Wonnam Kim, Woojin Kim, Hanbing Li. Modernization of Traditional Oriental Medicine: New Dosage Forms and Medical Instruments. Evidence-Based Complementary and Alternative Medicine. 2018; 2018 ():1-1.

Chicago/Turabian Style

Gihyun Lee; Wonnam Kim; Woojin Kim; Hanbing Li. 2018. "Modernization of Traditional Oriental Medicine: New Dosage Forms and Medical Instruments." Evidence-Based Complementary and Alternative Medicine 2018, no. : 1-1.

Journal article
Published: 05 December 2017 in International Journal of Molecular Sciences
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Oxaliplatin is a widely used chemotherapy agent, but induces serious peripheral neuropathy. Duloxetine is a dual reuptake inhibitor of serotonin and norepinephrine, and is shown to be effective against pain. However, whether and how duloxetine can attenuate oxaliplatin-induced allodynia in rodents is not clearly understood. A single injection of oxaliplatin (6 mg/kg, intraperitoneal; i.p.) induced a cold and mechanical allodynia, which was assessed by acetone and von Frey filament tests, respectively. When significant allodynic signs were observed, three different doses of duloxetine (10, 30, and 60 mg/kg, i.p.) were injected. Administration of 30 and 60 mg/kg of duloxetine significantly reduced the allodynia, whereas 10 mg/kg did not. By using an in vivo extracellular recording method, we further confirmed that 30 mg/kg of duloxetine could significantly inhibit the hyperexcitability of spinal wide dynamic range (WDR) cells. The anti-allodynic effect of duloxetine was completely blocked by an intrathecal injection of phentolamine (non-selective α-adrenergic receptor antagonist, 20 μg), or prazosin (α1-adrenergic receptor antagonists, 10 μg); however, idazoxan (α2-adrenergic receptor antagonist, 10 μg) did not block it. In conclusion, we suggest that duloxetine may have an effective protective action against oxaliplatin-induced neuropathic pain and spinal hyperexcitability, which is mediated by spinal α1-adrenergic receptors.

ACS Style

Woojin Kim; Yeongu Chung; Seunghwan Choi; Byung-Il Min; Sun Kwang Kim. Duloxetine Protects against Oxaliplatin-Induced Neuropathic Pain and Spinal Neuron Hyperexcitability in Rodents. International Journal of Molecular Sciences 2017, 18, 2626 .

AMA Style

Woojin Kim, Yeongu Chung, Seunghwan Choi, Byung-Il Min, Sun Kwang Kim. Duloxetine Protects against Oxaliplatin-Induced Neuropathic Pain and Spinal Neuron Hyperexcitability in Rodents. International Journal of Molecular Sciences. 2017; 18 (12):2626.

Chicago/Turabian Style

Woojin Kim; Yeongu Chung; Seunghwan Choi; Byung-Il Min; Sun Kwang Kim. 2017. "Duloxetine Protects against Oxaliplatin-Induced Neuropathic Pain and Spinal Neuron Hyperexcitability in Rodents." International Journal of Molecular Sciences 18, no. 12: 2626.

Journal article
Published: 31 October 2017 in Toxins
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Paclitaxel, a chemotherapy drug for solid tumors, induces peripheral painful neuropathy. Bee venom acupuncture (BVA) has been reported to have potent analgesic effects, which are known to be mediated by activation of spinal α-adrenergic receptor. Here, we investigated the effect of BVA on mechanical hyperalgesia and spinal neuronal hyperexcitation induced by paclitaxel. The role of spinal α-adrenergic receptor subtypes in the analgesic effect of BVA was also observed. Administration of paclitaxel (total 8 mg/kg, intraperitoneal) on four alternate days (days 0, 2, 4, and 6) induced significant mechanical hyperalgesic signs, measured using a von Frey filament. BVA (1 mg/kg, ST36) relieved this mechanical hyperalgesia for at least two hours, and suppressed the hyperexcitation in spinal wide dynamic range neurons evoked by press or pinch stimulation. Both melittin (0.5 mg/kg, ST36) and phospholipase A2 (0.12 mg/kg, ST36) were shown to play an important part in this analgesic effect of the BVA, as they significantly attenuated the pain. Intrathecal pretreatment with the α2-adrenergic receptor antagonist (idazoxan, 50 µg), but not α1-adrenergic receptor antagonist (prazosin, 30 µg), blocked the analgesic effect of BVA. These results suggest that BVA has potent suppressive effects against paclitaxel-induced neuropathic pain, which were mediated by spinal α2-adrenergic receptor.

ACS Style

Jiho Choi; Changhoon Jeon; Ji Hwan Lee; Jo Ung Jang; Fu Shi Quan; Kyungjin Lee; Woojin Kim; Sun Kwang Kim. Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α2-Adrenergic Receptor. Toxins 2017, 9, 351 .

AMA Style

Jiho Choi, Changhoon Jeon, Ji Hwan Lee, Jo Ung Jang, Fu Shi Quan, Kyungjin Lee, Woojin Kim, Sun Kwang Kim. Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α2-Adrenergic Receptor. Toxins. 2017; 9 (11):351.

Chicago/Turabian Style

Jiho Choi; Changhoon Jeon; Ji Hwan Lee; Jo Ung Jang; Fu Shi Quan; Kyungjin Lee; Woojin Kim; Sun Kwang Kim. 2017. "Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α2-Adrenergic Receptor." Toxins 9, no. 11: 351.

Review
Published: 18 October 2017 in Evidence-Based Complementary and Alternative Medicine
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The Locus Coeruleus (LC) is a small collection of noradrenergic neurons located in the pons. In the brain, noradrenaline (NE) is primarily produced by noradrenergic cell groups in the LC, which is the largest group of noradrenergic neurons in the central nervous system. Acupuncture, including the electroacupuncture which is a modified acupuncture method, is known to be effective in various kinds of diseases, and the involvement of noradrenergic system in the central nervous system has been reported by previous studies. However, on whether acupuncture can modulate the LC neuronal cells activities, results vary from studies to studies. In this paper, we included twelve articles, which observed the effect of acupuncture on the activities of LC in humans and animals. Our study shows that, among twelve included studies, six reported decrease of LC activities, whereas six showed increase of LC activities after acupuncture treatment. Although it is difficult to draw a firm conclusion, the authors suggest that the difference of frequencies may play an important role in the modulatory effect of acupuncture on LC. Further studies are needed to clarify the precise mechanism of acupuncture on LC, as it can lead to a new therapeutic method for various LC-NE related diseases.

ACS Style

Gihyun Lee; Woojin Kim. The Modulatory Effect of Acupuncture on the Activity of Locus Coeruleus Neuronal Cells: A Review. Evidence-Based Complementary and Alternative Medicine 2017, 2017, 1 -8.

AMA Style

Gihyun Lee, Woojin Kim. The Modulatory Effect of Acupuncture on the Activity of Locus Coeruleus Neuronal Cells: A Review. Evidence-Based Complementary and Alternative Medicine. 2017; 2017 ():1-8.

Chicago/Turabian Style

Gihyun Lee; Woojin Kim. 2017. "The Modulatory Effect of Acupuncture on the Activity of Locus Coeruleus Neuronal Cells: A Review." Evidence-Based Complementary and Alternative Medicine 2017, no. : 1-8.

Review
Published: 06 April 2017 in Journal of Neurochemistry
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Tissue or nerve injury induces widespread plastic changes from the periphery and spinal cord up to the cortex, resulting in chronic pain. Although many clinicians and researchers have extensively studied altered nociceptive signaling and neural circuit plasticity at the spinal cord level, effective treatments to ameliorate chronic pain are still insufficient. For about the last two decades, the rapid development in macroscopic brain imaging studies on humans and animal models have revealed maladaptive plastic changes in the ‘pain matrix’ brain regions, which may subsequently contribute to chronic pain. Among these brain regions, our group has concentrated for many years on the primary somatosensory (S1) cortex with a help of advanced imaging techniques and has found the functional and structural changes in neurons/glia as well as individual synapses in the S1 cortex during chronic pain. Taken together, it is now believed that such S1 plasticity is one of the causes for chronic pain, not a simple and passive epiphenomenon following tissue/nerve injury as previously thought. In this small review, we discuss the relation of plasticity in the S1 cortex with chronic pain, based on clinical trials and experimental studies conducted on this field. This article is part of the special article series “Pain”.

ACS Style

Woojin Kim; Sun Kwang Kim; Junichi Nabekura. Functional and structural plasticity in the primary somatosensory cortex associated with chronic pain. Journal of Neurochemistry 2017, 141, 499 -506.

AMA Style

Woojin Kim, Sun Kwang Kim, Junichi Nabekura. Functional and structural plasticity in the primary somatosensory cortex associated with chronic pain. Journal of Neurochemistry. 2017; 141 (4):499-506.

Chicago/Turabian Style

Woojin Kim; Sun Kwang Kim; Junichi Nabekura. 2017. "Functional and structural plasticity in the primary somatosensory cortex associated with chronic pain." Journal of Neurochemistry 141, no. 4: 499-506.

Journal article
Published: 14 January 2017 in BMC Complementary and Alternative Medicine
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Oxaliplatin, a widely used anticancer drug against metastatic colorectal cancer, can induce acute peripheral neuropathy, which is characterized by cold and mechanical allodynia. Activation of glial cells (e.g. astrocytes and microglia) and increase of pro-inflammatory cytokines (e.g. IL-1β and TNF-α) in the spinal cord play a crucial role in the pathogenesis of neuropathic pain. Our previous study demonstrated that Gyejigachulbu-Tang (GBT), a herbal complex formula, alleviates oxaliplatin-induced neuropathic pain in rats by suppressing spinal glial activation. However, it remains to be elucidated whether and how Buja (Aconiti Tuber), a major ingredient of GBT, is involved in the efficacy of GBT. Cold and mechanical allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) in Sprauge-Dawley rats were evaluated by a tail immersion test in cold water (4 °C) and a von Frey hair test, respectively. Buja (300 mg/kg) was orally administrated for five consecutive days after the oxaliplatin injection. Glial activation in the spinal cord was quantified by immunohistochemical staining using GFAP (for astrocytes) and Iba-1 (for microglia) antibodies. The amount of spinal pro-inflammatory cytokines, IL-1β and TNF-α, were measured by ELISA. Significant behavioral signs of cold and mechanical allodynia were observed 3 days after an oxaliplatin injection. Oral administration of Buja significantly alleviated oxaliplatin-induced cold and mechanical allodynia by increasing the tail withdrawal latency to cold stimuli and mechanical threshold. Immunohistochemical analysis showed the activation of astrocytes and microglia and the increase of the IL-1β and TNF-α levels in the spinal cord after an oxaliplatin injection. Administration of Buja suppressed the activation of spinal astrocytes without affecting microglial activation and down-regulated both IL-1β and TNF-α levels in the spinal cord. Our results indicate that Buja has a potent anti-allodynic effect in a rat model of oxaliplatin-induced neuropathic pain, which is associated with the inhibition of activation of astrocytes and release of pro-inflammatory cytokines in the spinal cord. Thus, our findings suggest that administration of Buja could be an alternative therapeutic option for the management of peripheral neuropathy, a common side-effect of oxaliplatin.

ACS Style

Yongjae Jung; Ji Hwan Lee; Woojin Kim; Sang Hyub Yoon; Sun Kwang Kim. Anti-allodynic effect of Buja in a rat model of oxaliplatin-induced peripheral neuropathy via spinal astrocytes and pro-inflammatory cytokines suppression. BMC Complementary and Alternative Medicine 2017, 17, 1 -8.

AMA Style

Yongjae Jung, Ji Hwan Lee, Woojin Kim, Sang Hyub Yoon, Sun Kwang Kim. Anti-allodynic effect of Buja in a rat model of oxaliplatin-induced peripheral neuropathy via spinal astrocytes and pro-inflammatory cytokines suppression. BMC Complementary and Alternative Medicine. 2017; 17 (1):1-8.

Chicago/Turabian Style

Yongjae Jung; Ji Hwan Lee; Woojin Kim; Sang Hyub Yoon; Sun Kwang Kim. 2017. "Anti-allodynic effect of Buja in a rat model of oxaliplatin-induced peripheral neuropathy via spinal astrocytes and pro-inflammatory cytokines suppression." BMC Complementary and Alternative Medicine 17, no. 1: 1-8.

Journal article
Published: 01 January 2017 in The Korean Journal of Physiology & Pharmacology
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Paclitaxel, a chemotherapeutic drug, induces severe peripheral neuropathy. Gabapentin (GBT) is a first line agent used to treat neuropathic pain, and its effect is mediated by spinal noradrenergic and muscarinic cholinergic receptors. Electro-acupuncture (EA) is used for treating various types of pain via its action through spinal opioidergic and noradrenergic receptors. Here, we investigated whether combined treatment of these two agents could exert a synergistic effect on paclitaxel-induced cold and mechanical allodynia, which were assessed by the acetone drop test and von Frey filament assay, respectively. Significant signs of allodynia were observed after four paclitaxel injections (a cumulative dose of 8 mg/kg, i.p.). GBT (3, 30, and 100 mg/kg, i.p.) or EA (ST36, Zusanli) alone produced dose-dependent anti-allodynic effects. The medium and highest doses of GBT (30 and 100 mg/kg) provided a strong analgesic effect, but they induced motor dysfunction in Rota-rod tests. On the contrary, the lowest dose of GBT (3 mg/kg) did not induce motor weakness, but it provided a brief analgesic effect. The combination of the lowest dose of GBT and EA resulted in a greater and longer effect, without inducing motor dysfunction. This effect on mechanical allodynia was blocked by spinal opioidergic (naloxone, 20 μg), or noradrenergic (idazoxan, 10 μg) receptor antagonist, whereas on cold allodynia, only opioidergic receptor antagonist blocked the effect. In conclusion, the combination of the lowest dose of GBT and EA has a robust and enduring analgesic action against paclitaxel-induced neuropathic pain, and it should be considered as an alternative treatment method.

ACS Style

Min Joon Kim; Ji Hwan Lee; Jo Ung Jang; Fu Shi Quan; Sun Kwang Kim; Woojin Kim. The efficacy of combination treatment of gabapentin and electro-acupuncture on paclitaxel-induced neuropathic pain. The Korean Journal of Physiology & Pharmacology 2017, 21, 657 -666.

AMA Style

Min Joon Kim, Ji Hwan Lee, Jo Ung Jang, Fu Shi Quan, Sun Kwang Kim, Woojin Kim. The efficacy of combination treatment of gabapentin and electro-acupuncture on paclitaxel-induced neuropathic pain. The Korean Journal of Physiology & Pharmacology. 2017; 21 (6):657-666.

Chicago/Turabian Style

Min Joon Kim; Ji Hwan Lee; Jo Ung Jang; Fu Shi Quan; Sun Kwang Kim; Woojin Kim. 2017. "The efficacy of combination treatment of gabapentin and electro-acupuncture on paclitaxel-induced neuropathic pain." The Korean Journal of Physiology & Pharmacology 21, no. 6: 657-666.