• The Korean Journal of Pain
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• v.37 no.2
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• pp.107-118
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• 2024

Nociplastic pain by the "International Association for the Study of Pain" is defined as pain that arises from altered nociception despite no clear evidence of nociceptive or neuropathic pain. Augmented central nervous system pain and sensory processing with altered pain modulation are suggested to be the mechanism of nociplastic pain. Clinical criteria for possible nociplastic pain affecting somatic structures include chronic regional pain and evoked pain hypersensitivity including allodynia with after-sensation. In addition to possible nociplastic pain, clinical criteria for probable nociplastic pain are pain hypersensitivity in the region of pain to non-noxious stimuli and presence of comorbidity such as generalized symptoms with sleep disturbance, fatigue, or cognitive problems with hypersensitivity of special senses. Criteria for definitive nociplastic pain is not determined yet. Eight specific disorders related to central sensitization are suggested to be restless leg syndrome, chronic fatigue syndrome, fibromyalgia, temporomandibular disorder, migraine or tension headache, irritable bowel syndrome, multiple chemical sensitivities, and whiplash injury; non-specific emotional disorders related to central sensitization include anxiety or panic attack and depression. These central sensitization pain syndromes are overlapped to previous functional pain syndromes which are unlike organic pain syndromes and have emotional components. Therefore, nociplastic pain can be understood as chronic altered nociception related to central sensitization including both sensory components with nociceptive and/or neuropathic pain and emotional components. Nociplastic pain may be developed to explain unexplained chronic pain beyond tissue damage or pathology regardless of its origin from nociceptive, neuropathic, emotional, or mixed pain components.

• The Korean Journal of Pain
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• v.22 no.1
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• pp.1-15
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• 2009

Neuropathic pain is often refractory to intervention because of the complex etiology and an incomplete understanding of the mechanisms behind this type of pain. Glial cells, specifically microglia and astrocytes, are powerful modulators of pain and new targets of drug development for neuropathic pain. Glial activation could be the driving force behind chronic pain, maintaining the noxious signal transmission even after the original injury has healed. Glia express chemokine, purinergic, toll-like, glutaminergic and other receptors that enable them to respond to neural signals, and they can modulate neuronal synaptic function and neuronal excitability. Nerve injury upregulates multiple receptors in spinal microglia and astrocytes. Microglia influence neuronal communication by producing inflammatory products at the synapse, as do astrocytes because they completely encapsulate synapses and are in close contact with neuronal somas through gap junctions. Glia are the main source of inflammatory mediators in the central nervous system. New therapeutic strategies for neuropathic pain are emerging such as targeting the glial cells, novel pharmacologic approaches and gene therapy. Drugs targeting microglia and astrocytes, cytokine production, and neural structures including dorsal root ganglion are now under study, as is gene therapy. Isoform-specific inhibition will minimize the side effects produced by blocking all glia with a general inhibitor. Enhancing the anti-inflammatory cytokines could prove more beneficial than administering proinflammatory cytokine antagonists that block glial activation systemically. Research on therapeutic gene transfer to the central nervous system is underway, although obstacles prevent immediate clinical application.

• The Korean Journal of Pain
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• v.34 no.1
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• pp.35-46
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• 2021

Background: The present investigation explored the therapeutic actions of oleuropein along with the possible signaling pathway involved in attenuating neuropathic pain in chronic constriction injury (CCI) and vincristine-induced neuropathic pain in male rats. Methods: Four loose ligatures were placed around the sciatic nerve to induce CCI, and vincristine (50 ㎍/kg) was injected for 10 days to develop neuropathic pain. The development of cold allodynia, mechanical allodynia, and mechanical hyperalgesia was assessed using different pain-related behavioral tests. The levels of H2S, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), orexin, and nuclear factor erythroid-2-related factor 2 (Nrf2) were measured in the sciatic nerve. Results: Treatment with oleuropein for 14 days led to significant amelioration of behavioral manifestations of neuropathic pain in two pain models. Moreover, oleuropein restored both CCI and vincristine-induced decreases in H2S, CSE, CBS, orexin, and Nrf2 levels. Co-administration of suvorexant, an orexin receptor antagonist, significantly counteracted the pain-attenuating actions of oleuropein and Nrf2 levels without modulating H2S, CSE and CBS. Conclusions: Oleuropein has therapeutic potential to attenuate the pain manifestations in CCI and vincristine-induced neuropathic pain, possibly by restoring the CSE, CBS, and H2S, which may subsequently increase the expression of orexin and Nrf2 to ameliorate behavioral manifestations of pain.

• The Journal of the Korean dental association
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• v.49 no.6
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• pp.321-326
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• 2011

Neuropathic pain is caused by functional abnonnalities of structural lesions in the peripheral or central nervous system, and occurs without peripheral nociceptor stimulation. Trigeminal neuropathy always pose differential location difficulties as multiple diseases are capablc of producing them: they can be the result of traumatism, tumors, or diseases of the connective tissue, infectious or demyelinating diseases, or may be of idiopathic origin. There are a number of mechanisms described as causing neuropathy. They can be described as ectopic nerve activity, neuroma, ephatic trasmission, change of sodium channel expression, sympathetic activity, central sensitization, and alteration in central inhibition systems. More than I mechanism may be active to create individual clinical presentations. In order to provide better pain control, the mechanism-based approach in treating neuropathic pain should be familiar to physicians.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.18 no.1
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• pp.50-60
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• 2005

Objective : We have studied to know effects of Ligigeopoongsan(LGS, 理氣祛風散) on mechanical allodynia, cold allodynia and c-Fos protein expression in the model of neuropathic pain of rats. Methods : The model of neuropathic pain was made by injured tibial nerve and sural never while common peroneal never was maintained. After 2weeks, we performed behavioral test for 7 days to try out mechanical allodynia using von frey filament and cold allodynia using acetone, which are calculated by counting withdrawal response on foot. Rat brains removed and sliced on 8th days. Serial sections were immunohistochemically reacted with polyclonal c-Fos antibody. The numbers of c-Fos protein immunoreactive neurons in the central gray were examined using scion image program. Results : 1. Mechanical allodynia in LGS-2, LGS-3 groups were significantly diminished compared with the control group. 2. Cold allodynia in LGS-3 group was significantly diminished compared with the control group. 3. c-Fos protein expression on the central gray LGS-2, LGS-3 groups were significantly lower than that of control group. conclusions : We have noticed that LGS(理氣祛風散) diminished mechanical and cold allodynia in the model of neuropathic pain compared with the control group. c-Fos protein expression in the central gray of that group was also decreased compared with the control group. Pain control group were LGS was accumulated time goes by. This study can be used as a basic resource on a study and a treatment of pain.

• The Korean Journal of Pain
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• v.33 no.3
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• pp.216-225
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• 2020

Background: Garlic oil is a rich source of organosulfur compounds including diallyl disulfide and diallyl trisulfide. There have been studies showing the neuroprotective actions of these organosulfur compounds. However, the potential of these organosulfur compounds in neuropathic pain has not been explored. The present study was aimed at investigating the pain attenuating potential of diallyl disulfide and diallyl trisulfide in chronic constriction injury (CCI)-induced neuropathic pain in rats. The study also explored their pain-attenuating mechanisms through modulation of H₂S, brain-derived neurotrophin factor (BDNF) and nuclear factor erythroid 2-related factor 2 (Nrf2). Methods: The rats were subjected to CCI injury by ligating the sciatic nerve in four places. The development of neuropathic pain was measured by assessing mechanical hyperalgesia (Randall-Selittotest), mechanical allodynia (Von Frey test), and cold allodynia (acetone drop test) on 14th day after surgery. Results: Administration of diallyl disulfide (25 and 50 mg/kg) and diallyl trisulfide (20 and 40 mg/kg) for 14 days led to a significant reduction in pain in CCI-subjected rats. Moreover, treatment with these organosulfur compounds led to the restoration of H₂S, BDNF and Nrf2 levels in the sciatic nerve and dorsal root ganglia. Co-administration of ANA-12 (BDNF blocker) abolished pain attenuating actions as well as BDNF and the Nrf2 restorative actions of diallyl disulfide and diallyl trisulfide, without modulating H₂S levels. Conclusions: Diallyl disulfide and diallyl trisulfide have the potential to attenuate neuropathic pain in CCI-subjected rats possibly through activation of H₂S-BDNF-Nrf2 signaling pathway.

• International Journal of Oral Biology
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• v.45 no.3
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• pp.84-91
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• 2020

The present study investigated the participation of D-serine and NR2 in antinociception produced by blockade of central erythropoietin-producing hepatocellular carcinoma (Eph) A4 (EphA4) signaling in rats with trigeminal neuropathic pain. Trigeminal neuropathic pain was modeled in male Sprague-Dawley rats using mal-positioned dental implants. The left mandibular second molar was extracted under anesthesia, and a miniature dental implant was placed to induce injury to the inferior alveolar nerve. Our current findings showed that nerve injury induced by malpositioned dental implants significantly produced mechanical allodynia; additionally, the inferior alveolar nerve injury increased the expression of D-serine and NR2 subunits in the ipsilateral medullary dorsal horn (trigeminal subnucleus caudalis). Intracisternal administration of EphA4-Fc, an EphA4 inhibitor, inhibited nerve injury-induced mechanical allodynia and upregulated the expression of D-serine and NR2 subunits. Moreover, intracisternal administration of D-amino acids oxidase, a D-serine inhibitor, inhibited trigeminal mechanical allodynia. These results show that D-serine and NR2 subunit pathways participate in central EphA4 signaling after an inferior alveolar nerve injury. Therefore, blockade of D-serine and NR2 subunit pathways in central EphA4 signaling provides a new therapeutic target for the treatment of trigeminal neuropathic pain.

• IMMUNE NETWORK
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• v.12 no.2
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• pp.41-47
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• 2012

Contemporary studies illustrate that peripheral injuries activate glial components of the peripheral and central cellular circuitry. The subsequent release of glial stressors or activating signals contributes to neuropathic pain and neuroinflammation. Recent studies document the importance of glia in the development and persistence of neuropathic pain and neuroinflammation as a connecting link, thereby focusing attention on the glial pathology as the general underlying factor in essentially all age-related neurodegenerative diseases. There is wide agreement that excessive glial activation is a key process in nervous system disorders involving the release of strong pro-inflammatory cytokines, which can trigger worsening of multiple disease states. This review will briefly discuss the recent findings that have shed light on the molecular and cellular mechanisms of glia as a connecting link between neuropathic pain and neuroinflammation.

• The Korean Journal of Pain
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• v.27 no.3
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• pp.246-252
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• 2014

Background: Neuropathic pain is generally defined as a chronic pain state resulting from peripheral and/or central nerve injury. There is a lack of effective treatment for neuropathic pain, which may possibly be related to poor understanding of pathological mechanisms at the molecular level. Curcumin, a therapeutic herbal extract, has shown to be effectively capable of reducing chronic pain induced by peripheral administration of inflammatory agents such as formalin. In this study, we aimed to show the effect of curcumin on pain behavior and serum COX-2 level in a Chronic Constriction Injury (CCI) model of neuropathic pain. Methods: Wistar male rats (150-200 g, n = 8) were divided into three groups: CCI vehicle-treated, sham-operated, and CCI drug-treated group. Curcumin (12.5, 25, 50 mg/kg, IP) was injected 24 h before surgery and continued daily for 7 days post-surgery. Behavioral tests were performed once before and following the days 1, 3, 5, 7 after surgery. The serum COX-2 level was measured on day 7 after the surgery. Results: Curcumin (50 mg/kg) decreased mechanical and cold allodynia (P < 0.001) and produced a decline in serum COX-2 level (P < 0.001). Conclusions: A considerable decline in pain behavior and serum COX-2 levels was seen in rat following administration of curcumin in CCI model of neuropathic pain. High concentration of Curcumin was able to reduce the chronic neuropathic pain induced by CCI model and the serum level of COX-2.

• Journal of Acupuncture Research
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• v.22 no.5
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• pp.67-77
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• 2005

Objectives : The purpose of this study is to examine if Bee Venom Acupuncture may be effective to the neuropathic pain(mechanical allodynia, cold allodynia) in a rat model of neuropathic pain. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, tibial nerve and sural nerve was resected. After the neuropathic surgery, the author examined if the animals exhibited the behavioral signs of alloynia. The allodynia was assessed by stimulating the medial malleolus with von Frey filament and acetone. Three weeks after the neuropathic surgery, Bee Venom Acupuncture was injected at Hwando(GB30) one time a day for one week. After that, the author examined the withdrawl response of neuropathic rats' legs by yon Frey filament and acetone stimulation. And also the author examined c-Fos in the midbrain central gray of neuropathic rats and the change of WBC count in the blood of neuropathic rats. Results : The Bee Venom Acupuncture injected Hwando(GB30) decreased the withdrawl response of mechanical allodynia in BV-2, BV-3 group as compared with control group. The Bee Venom Acupuncture injected Hwando(GB30) decreased the withdrawl response of chemical allodynia(cold allodynia) in BV-2, BV-3 group as compared with control group. The Bee Venom Acupuncture injected Hwando(GB30) showed the significant difference between control group and BV-2 group, control group and BV-3 group in the c-Fos expression and U count. Conclusion : We have noticed that Bee Venom Acupuncture at Hwando(GB30) decreased mechanical allodynia and cold allodynia in the model of neuropathic pain compared with the control group. C-Fos expression in the central gray of that group was also decreased compared with the control group. Psin control using Bee Venom Acupuncture was accumulated as time goes by. This study can be used as a basic resource on a study and a treatment of pain.