• Korean Journal of Acupuncture
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• v.38 no.2
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• pp.75-99
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• 2021

Objectives : The purpose of this study is to analyze animal behavioral changes and related neurobiological mechanisms in recent studies using animal models with pain and depression. Methods : We conducted database search in Pubmed, NDSL, and EMBASE up to January 2021. Included studies were classified as depression-like behavior observed in pain model, pain-like behavior observed in depression model, and pain and depression comorbidity model. The results of pain- and depression-like behaviors, the changes of neurobiological mechanisms, and the treatment methods such as drugs, natural substance-derived chemicals, or acupuncture were analyzed. Results : We included 124 studies (81 studies in depression-like behavior observed in pain model, 19 studies in pain-like behavior observed in depression model, and 24 studies in pain and depression comorbidity model). Pain and depression comorbidity animal models were induced using various methods by drugs or surgery. Von frey test, a method for evaluating mechanical allodynia was the most commonly used for measuring pain-like behavior and the forced swimming test was the most commonly used for measuring depression-likes behavior. The changes of neurobiological factors, such as decrease of 5-hydroxytryptamine and increase of oxidative stress and pro-inflammation cytokines were generally changed in the frontal cortex, hippocampus, thalamus, and spinal cord in all types of models. For treating pain and depression-like behaviors, various types of drugs such as antidepressant, tranquilizer, analgesic, and natural substance-derived chemicals were used. Acupuncture treatment was used in 4 studies. Conclusions : In the future, more diverse studies on the combined model of pain and depression need to be conducted. In addition, it is necessary to establish a mechanistic basis for the development of various treatments by identifying the common mechanisms of pain and depression.

• Biomedical Science Letters
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• v.29 no.3
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• pp.152-158
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• 2023

The aim of this study is to investigate the analgesic effects of Syneilesis aconitifolia Maxim. extract (SAM). We evaluated analgesic effects of SAM on animal pain model. Male SD rats were administered intra-orally with SAM according to prescribed dosage. During 7 days. After 7 days later, serum TNF-α, IL-1β, and IL-6 levels were measured by ELISA. In our experiment, administration of SAM decreased IL-1β, IL-6, TNF-α and PGE2 level in serum. Furthermore, it was confirmed that allodynia was relieved in evaluation of pain behavior. It was confirmed that administration of SAM reduces nociceptive pain by reducing nociceptive stimuli by acting as an anti-inflammatory drug.

• The Korean Journal of Pain
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• v.13 no.1
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• pp.19-30
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• 2000

Background: Partial nerve injury to a peripheral nerve may induce the development of neuropathic pain which is characterized by symptoms such as spontaneous burning pain, allodynia and hyperalgesia. Though underlying mechanism has not fully understood, sensitization of dorsal horn neurons may contribute to generate such symptoms. Nitric oxide acts as an inter- and intracellular messenger in the nervous system and is produced from L-arginine by nitric oxide synthase (NOS). Evidence is accumulating which indicate that nitric oxide may mediate nociceptive information transmission. Recently, it has been reported that NOS inhibitor suppresses neuropathic pain behavior in an neuropathic pain animal model. This study was conducted to determine whether nitric oxide could be involved in the sensitization of dorsal horn neurons in neuropathic animal model. Methods: Neuropathic animal model was made by tightly ligating the left L5 and L6 spinal nerves and we examined the effects of iontophoretically applied NOS inhibitor (L-NAME) on the dorsal horn neuron's responses to mechanical stimuli within the receptive fields. Results: In normal animals, NOS inhibitor (L-NAME) specifically suppressed the responses to the noxious mechanical stimuli. In neuropathic animals, the dorsal horn neuron's responses to mechanical stimuli were enhanced and NOS inhibitor suppressed the dorsal horn neuron's enhanced responses to non-noxious stimuli as well as those to noxious ones. Conclusions: These results suggest that nitric oxide may mediate nociceptive transmission in normal animal and also mediate sensitization of dorsal horn neurons in neuropathic pain state.

• The Korean Journal of Pain
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• v.8 no.1
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• pp.25-30
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• 1995

Anlgesic agents against visceral pain typically rely on a noxious chemical irritation of the peritoneum, e. g., acetic acid and phenylquinone writhing test. While useful, this type of assay depends upon an acute inflammation and the release of local alogens. Further, ethical and scientific constraints prevent repeated assessments in a single animal, thereby compounding the difficulty of assessing tolerance development to analgesic agents. To overcome these constraints, Colburn et al. developed a model for mechanical visceral pain model (VPM) based on a repeatable and reversible duodenal distention in the rat. A chronic indwelling intraduodenal balloon catheter is well tolerated and upon inflation produces a writhing response graded in proportion to distention. This response is inhibited by morphine in a dose dependent manner. We found that a model for visceral pain was thought to be a great value.

• The Korean Journal of Pain
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• v.34 no.2
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• pp.165-175
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• 2021

Background: Management of pain from open wounds is a growing unmet healthcare need. However, the models available to study pain from wounds or to develop analgesics for the patients suffering from them have primarily relied on incisional models. Here, we present the first characterized and validated model of open wound pain. Methods: Unilateral full-skin excisional punch biopsy wounds on rat hind paws were evaluated for evoked pain using withdrawal responses to mechanical and thermal stimulation, and spontaneous pain was measured using hind paw weight distribution and guarding behavior. Evaluations were done before wounding (baseline) and 2-96 hours post-wounding. The model was validated by testing the effects of buprenorphine and carprofen. Results: Pain responses to all tests increased within 2 hours post-wounding and were sustained for at least 4 days. Buprenorphine caused a reversal of all four pain responses at 1 and 4 hours post-treatment compared to 0.9% saline (P < 0.001). Carprofen decreased the pain response to thermal stimulation at 1 (P ≤ 0.049) and 4 hours (P < 0.011) post-treatment compared to 0.9% saline, but not to mechanical stimulation. Conclusions: This is the first well-characterized and validated model of pain from open wounds and will allow study of the pathophysiology of pain in open wounds and the development of wound-specific analgesics.

• Journal of Life Science
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• v.20 no.4
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• pp.496-502
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• 2010

The acidic saline animal model of pain has been suggested to mimic fibromyalgia (FM). Oligomeric proanthocyanidin complexes (OPC) from grape seeds are known to act as an antioxidant. We studied the effects of OPC on the pain threshold in the acidic saline animal model of pain. The left gastrocnemius muscle was injected with $100\;{\mu}l$ of saline at pH 4.0 under brief isoflurane anesthesia on days 0 and 5. Control rats (n=5) received identical injections of physiological saline (pH 7.2) on the same schedule. Rats (n=10) with acidic saline injection were separated into two study subgroups. After measurement of pre-drug pain thresholds, rats were injected intraperitoneally with either saline or OPC 300 mg/kg. Paw withdrawal thresholds to pressure were again measured 60 min after intraperitoneal injection. Nociceptive thresholds were measured with a Dynamic Plantar Aesthesiometer by applying an increasing pressure to right or left hind paw until the rat withdrew the paw. Compared to baseline (day 0), acid injections produced mechanical hyper-responsiveness on day 7 (pre-drug) in these rats [p<0.05]. A potent antihyperalgesic effect was observed when rats were injected intraperitoneally with OPC 300 mg/kg [injected paw, p=0.001; contralateral paw, p=0.002]. OPC treatment decreased the expression of acid sensing ion channel 3 in the brain motor cortex area on immunohistochemical staining when OPC 300 mg/kg was administered intraperitoneally in the animal model of FM pain [p<0.05]. Further research is required to determine the efficacy of OPC treatments in FM pain in humans.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.163-167
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• 2013

In the present study, the effect of intrathecal (i.t.) or intracerebroventricular (i.c.v.) administration with cholera toxin (CTX) on the blood glucose level was examined in ICR mice. The i.t. treatment with CTX alone for 24 h dose-dependently increased the blood glucose level. However, i.c.v. treatment with CTX for 24 h did not affect the blood glucose level. When mice were orally fed with D-glucose (2 g/kg), the blood glucose level reached to a maximum level at 30 min and almost returned to the control level at 120 min after D-glucose feeding. I.c.v. pretreatment with CTX increased the blood glucose level in a potentiative manner, whereas i.t. pretreatment with CTX increased the blood glucose level in an additive manner in a D-glucose fed group. In addition, the blood glucose level was increased in formalin-induced pain animal model. I.c.v. pretreatment with CTX enhanced the blood glucose level in a potentiative manner in formalin-induced pain animal model. On the other hand, i.t. pretreatment with CTX increased the blood glucose level in an additive manner in formalin-induced pain animal model. Our results suggest that CTX administered supraspinally or spinally differentially modulates the regulation of the blood glucose level in D-glucose fed model as well as in formalin-induced pain model.

• The Korean Journal of Pain
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• v.33 no.2
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• pp.131-137
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• 2020

Background: Among various diseases that accompany pain, complex regional pain syndrome (CRPS) is one of the most frustrating for patients and physicians. Recently, many studies have shown functional and anatomical abnormalities in the brains of patients with CRPS. The calcium-related signaling pathway is important in various physiologic processes via calmodulin (CaM) and calcium-calmodulin kinase 2 (CaMK2). To investigate the cerebral mechanism of CRPS, we measured changes in CaM and CaMK2 expression in the cerebrum in CRPS animal models. Methods: The chronic post-ischemia pain model was employed for CRPS model generation. After generation of the animal models, the animals were categorized into three groups based on changes in the withdrawal threshold for the affected limb: CRPS-positive (P), CRPS-negative (N), and control (C) groups. Western blot analysis was performed to measure CaM and CaMK2 expression in the rat cerebrum. Results: Animals with a decreased withdrawal threshold (group P) showed a significant increment in cerebral CaM and CaMK2 expression (P = 0.013 and P = 0.021, respectively). However, groups N and C showed no difference in CaM and CaMK2 expression. Conclusions: The calcium-mediated cerebral process occurs after peripheral injury in CRPS, and there can be a relationship between the cerebrum and the pathogenesis of CRPS.

• Annals of Clinical Neurophysiology
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• v.11 no.2
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• pp.41-47
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• 2009

Background: Discogenic pain can develop into chronic low back pain that is very difficult to treat effectively, because the pathogenesis of the disease still remains controversial. To clarify the pathogenesis, numerous animal models of intervertebral disc degeneration have been proposed in the literature, each with attendant advantages and disadvantages. The aim of this study was to determine the most efficacious method and dose of complete Freund's adjuvant (CFA) injection into intervertebral disc to develop a discogenic pain in a rat. Methods: CFA was injected into the L5-L6 or L4-L5 disc of male Sprague-Dawley rats in various conditions including a dose of CFA (10, 20, or 50 uL), drilling, injection site sealing using cyanoacrylate, and injection velocity. Sham animals were subjected to the same procedure, except for the CFA injection. Mechanical and heat allodynia were serially measured at both hindpaws until 8 weeks post-operatively. Serial MRI analyses were performed to observe degenerative changes of the discs. In addition, CGRP & Substance P-immunoreactivities (ir) in the superficial dorsal horn were evaluated at 4 weeks using immunohistochemistry. Results: Each condition provoked various problems such as development of hindpaw paralysis, CFA leakage, and no pain development. Mid-sagittal T2 MRI revealed no significant degenerative changes in the CFA injected disc. The CGRP-ir of the bilateral superficial dorsal horns at the level of L5-L6 was significantly increased in the CFA group. Conclusions: A total of 10 uL CFA injection into L5-L6 disc for a period of 10 minutes using a 26-gauge needle without drilling was the most efficacious way to develop discogenic pain animal model.

• BMB Reports
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• v.55 no.5
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• pp.205-212
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• 2022

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disorder characterized by suprapubic pain and urinary symptoms such as urgency, nocturia, and frequency. The prevalence of IC/BPS is increasing as diagnostic criteria become more comprehensive. Conventional pharmacotherapy against IC/BPS has shown suboptimal effects, and consequently, patients with end-stage IC/BPS are subjected to surgery. The novel treatment strategies should have two main functions, anti-inflammatory action and the regeneration of glycosaminoglycan and urothelium layers. Stem cell therapy has been shown to have dual functions. Mesenchymal stem cells (MSCs) are a promising therapeutic option for IC/BPS, but they come with several shortcomings, such as immune activation and tumorigenicity. MSC-derived extracellular vesicles (MSC-EVs) hold numerous therapeutic cargos and are thus a viable cell-free therapeutic option. In this review, we provide a brief overview of IC/BPS pathophysiology and limitations of the MSC-based therapies. Then we provide a detailed explanation and discussion of therapeutic applications of EVs in IC/BPS as well as the possible mechanisms. We believe our review will give an insight into the strengths and drawbacks of EV-mediated IC/BPS therapy and will provide a basis for further development.