• The Korean Journal of Pain
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• 제35권1호
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• pp.43-58
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• 2022

Background: Current therapies are quite unsuccessful in the management of neuropathic pain. Therefore, considering the inhibitory characteristics of GABA mediators, the present systematic review and meta-analysis aimed to determine the efficacy of GABAergic neural precursor cells on neuropathic pain management. Methods: Search was conducted on Medline, Embase, Scopus, and Web of Science databases. A search strategy was designed based on the keywords related to GABAergic cells combined with neuropathic pain. The outcomes were allodynia and hyperalgesia. The results were reported as a pooled standardized mean difference (SMD) with a 95% confidence interval (95% CI). Results: Data of 13 studies were analyzed in the present meta-analysis. The results showed that administration of GABAergic cells improved allodynia (SMD = 1.79; 95% CI: 0.87, 271; P < 0.001) and hyperalgesia (SMD = 1.29; 95% CI: 0.26, 2.32; P = 0.019). Moreover, the analyses demonstrated that the efficacy of GABAergic cells in the management of allodynia and hyperalgesia is only observed in rats. Also, only genetically modified cells are effective in improving both of allodynia, and hyperalgesia. Conclusions: A moderate level of pre-clinical evidence showed that transplantation of genetically-modified GABAergic cells is effective in the management of neuropathic pain. However, it seems that the transplantation efficacy of these cells is only statistically significant in improving pain symptoms in rats. Hence, caution should be exercised regarding the generalizability and the translation of the findings from rats and mice studies to large animal studies and clinical trials.

• Annals of Clinical Neurophysiology
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• 제11권2호
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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.

• 생명과학회지
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• 제20권4호
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• pp.496-502
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• 2010

산성 식염수 쥐모델은 사람의 섬유근통에 근접한 모델로 제시되고 있다. 포도씨에서 얻은 oligomeric proanthocyanidin complexes (OPC)는 항산화제로 알려져 있다. 저자들은 산성 식염수 모델에서 통증 역치에 대한 OPC의 효과를 연구했다. 좌측 장딴지 근육에 pH 4.0의 산성 식염수 $100\;{\mu}l$를 0일과 5일에 주사했다. 대조군은 pH 7.2의 생리 식염수를 같은 스케줄로 주사했다. 산성 식염수 그룹 10마리를 다시 두 그룹으로 나누어 한 그룹은 멸균 식염수, 다른 한 그룹은 OPC 300 mg/kg를 복강 내 주사했다. 복강 내 주사 한시간 후 다시 통각에 대한 역치를 조사했다. 0일에 비해 7일에서 산성 식염수 모델은 기계적 과통각을 나타냈다(p<0.05). OPC 300 mg/kg를 복강내 주사한 그룹에서 강력한 항통각 효과를 나타냈다(주사측 발바닥, p=0.001; 반대측 발바닥, p=0.002). 면역조직화학 염색상 복강내 식염수를 처치한 대조군에 비해 OPC 처치군에서 대뇌의 M1 및 M2 영역에서 산-감지 이온 통로3의 발현이 감소되었다(p<0.05). 사람의 섬유근통에서 OPC 치료의 효과를 보기 위한 연구가 향후 필요할 것으로 생각된다.

• 한국임상수의학회지
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• 제22권1호
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• pp.6-15
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• 2005

본 연구는 개에서 장문합술 후 비침습적인 행동관찰을 통해 통증을 평가하기 위하여 수행되었으며, 또한 이를 토대로 butorphanol의 진통효과에 대해 연구하였다. 본 실험에서 대조군은 마취를 실시하였으나 장문합술은 시행되지 않았다. 진통제 투여군의 5마리 개들에게는 장문합술을 실시하였고 butorphanol을 투여하였다. 진통제 비투여군의 5마리 개들에게는 진통제 투여 없이 장문합술을 실시하였다. 진통제 투여군의 개들은 수술 전 그리고 수술직후 butorphanol(0.4mg/kg, IM)이 투여되었고, 반면에 대조군과 진통제를 투여하지 않은 군에서는 동일한 양의 멸균 생리식염수가 투여되었다. 개의 행동은 마취 후 400분 동안 비디오테이프로 기록되었고, 그 시간에 실험자는 매 80분마다 개와 상호작용을 하였다. 각각의 상호작용에서, 실험자는 관찰된 행동을 바탕으로 멜버른 대학의 통증 측정방법을 이용하여 통증 점수를 기록하였다. 한 사람의 관찰자에 의해 정량화 된 상호작용과 비 상호작용의 행동을 측정하기 위하여 한 개체에 집중하는 연속적 표본 추출 방법이 적용되었다. 발성은 마취 후 400분 동안 녹음하였고 소리 길이, 소리 강도, 소리 pitch와 1-4 포먼트를 분석하였다. 외과수술은 통증측정 점수를 증가시켰다. 실험자와의 상호작용 중에서 수술 후 인사하는 행동이 감소되었다. 진통제를 투여한 수술군과 위약을 투여한 군사이의 차이점은 정량화된 행동측정과 발성을 통하여 구별할 수 있었다. Butorphanol을 투여한 수술군과 위약을 투여한 군 사이에는 유의적인 차이를 관찰할 수 있었다 (p< 0.05).

• The Korean Journal of Pain
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• 제34권2호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제17권2호
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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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• 제8권1호
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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.

• 한국동물생명공학회지
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• 제37권1호
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• pp.13-16
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• 2022

The use of animals heavily impacts the mental health of researchers performing the animal experiments. The animal researchers need to take care of animals but also give pain and sacrifice them at the same time. This circumstance can cause a variety of mental stress to the researchers. The stress generated in the laboratory would not only negatively affect the management of animals and the research results, but also would harm the researchers' physical and mental health. Because the feeling of sympathy for animals is a natural feature of humanity, psychological stress following a laboratory animal's death after use is not surprising. It is necessary to revise the relevant laws based on understanding the difficulties of animal researchers in society and to develop related educational programs at the national level to help the psychology and emotions of researchers who conduct animal experiments.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.1-8
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• 2016

Damage in the periphery or spinal cord induces maladaptive plastic changes along the somatosensory nervous system from the periphery to the cortex, often leading to chronic pain. Although the role of neural circuit remodeling and structural synaptic plasticity in the 'pain matrix' cortices in chronic pain has been thought as a secondary epiphenomenon to altered nociceptive signaling in the spinal cord, progress in whole brain imaging studies on human patients and animal models has suggested a possibility that plastic changes in cortical neural circuits may actively contribute to chronic pain symptoms. Furthermore, recent development in two-photon microscopy and fluorescence labeling techniques have enabled us to longitudinally trace the structural and functional changes in local circuits, single neurons and even individual synapses in the brain of living animals. These technical advances has started to reveal that cortical structural remodeling following tissue or nerve damage could rapidly occur within days, which are temporally correlated with functional plasticity of cortical circuits as well as the development and maintenance of chronic pain behavior, thereby modifying the previous concept that it takes much longer periods (e.g. months or years). In this review, we discuss the relation of neural circuit plasticity in the 'pain matrix' cortices, such as the anterior cingulate cortex, prefrontal cortex and primary somatosensory cortex, with chronic pain. We also introduce how to apply long-term in vivo two-photon imaging approaches for the study of pathophysiological mechanisms of chronic pain.

• The Korean Journal of Physiology and Pharmacology
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• 제23권1호
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• pp.1-20
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• 2019

Neuropathic pain is a complex chronic pain state caused by the dysfunction of somatosensory nervous system, and it affects the millions of people worldwide. At present, there are very few medical treatments available for neuropathic pain management and the intolerable side effects of medications may further worsen the symptoms. Despite the presence of profound knowledge that delineates the pathophysiology and mechanisms leading to neuropathic pain, the unmet clinical needs demand more research in this field that would ultimately assist to ameliorate the pain conditions. Efforts are being made globally to explore and understand the basic molecular mechanisms responsible for somatosensory dysfunction in preclinical pain models. The present review highlights some of the novel molecular targets like D-amino acid oxidase, endoplasmic reticulum stress receptors, sigma receptors, hyperpolarization-activated cyclic nucleotide-gated cation channels, histone deacetylase, $Wnt/{\beta}-catenin$ and Wnt/Ryk, ephrins and Eph receptor tyrosine kinase, Cdh-1 and mitochondrial ATPase that are implicated in the induction of neuropathic pain. Studies conducted on the different animal models and observed results have been summarized with an aim to facilitate the efforts made in the drug discovery. The diligent analysis and exploitation of these targets may help in the identification of some promising therapies that can better manage neuropathic pain and improve the health of patients.