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疼痛疾病模型

疾病簡介

國際疼痛研究協(xié)會(huì)將疼痛(Pain)定義為一種與實(shí)際或潛在的組織損傷相關(guān)的不愉快的感官和情感體驗(yàn),它是身體為了避免進(jìn)一步傷害的自我保護(hù)機(jī)制。目前臨床上使用鎮(zhèn)痛藥物如非甾體抗炎藥(NSAIDs)、阿片類藥物、局部麻醉藥等,結(jié)合其他的管理策略,可以有效減輕患者的疼痛癥狀,提高生活質(zhì)量。但這些藥物的使用過程中,仍會(huì)出現(xiàn)不可避免的副作用、耐藥性以及潛在的成癮風(fēng)險(xiǎn)。

疾病模型

嚙齒類動(dòng)物是臨床前疼痛動(dòng)物模型使用最廣泛的模式生物。通過物理、化學(xué)或遺傳學(xué)等手段誘導(dǎo)動(dòng)物產(chǎn)生與人類相似的疼痛反應(yīng),觀察并記錄動(dòng)物的行為變化以評估疼痛程度,可以幫助科學(xué)家們探索疼痛的發(fā)生機(jī)制、篩選新型鎮(zhèn)痛藥物靶點(diǎn)、評估新型鎮(zhèn)痛藥物的療效和安全性。

福爾馬林(formain)致痛模型是一種常用的疼痛模型,僅需將適量福爾馬林注射至小鼠后足背部皮下,通過觀察小鼠舔爪的時(shí)間判斷小鼠疼痛情況。福爾馬林所致的痛行為學(xué)分為兩個(gè)時(shí)相(第一期為注射后10min左右,第二期則從注射后約15-20min開始,持續(xù)60min以上),非類固醇抗炎藥對第一期疼痛無效但可減弱第二期的疼痛,這種疼痛一般認(rèn)為與中樞敏化作用有關(guān),研究這類疼痛對于臨床上組織損傷造成的痛覺過敏機(jī)制探討極為重要。

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Fig1. Formain induced?pain models. Pain-like behaviors were observed in mice within minutes of injection, manifested by licking the soles of the feet.?The formalin pain model is acute and the pain goes away within hours.

卡拉膠(又名角叉菜膠,Carrageenan,CG)是一種強(qiáng)化學(xué)物質(zhì),用于刺激釋放炎癥和促炎介質(zhì)(包括前列腺素、白三烯、組胺、血清素、緩激肽和TNF-a等)。在實(shí)驗(yàn)動(dòng)物的足爪、肌肉、關(guān)節(jié)等部位注射角叉菜膠,最初引起急性炎癥,2周后可轉(zhuǎn)化成慢性炎癥,該模型主要用于了解急性炎性痛以及模擬組織損傷的條件,如關(guān)節(jié)扭傷、拉傷、肌炎。

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Fig1.?Carrageenan-induced pain models. Mice exhibit mechanical algesia and thermal algesia after injection.?The chronic inflammatory pain model induced by carrageenan can last for days.?

半保留神經(jīng)損傷(SNI)模型通過結(jié)扎部分坐骨神經(jīng)分支造模,這種模型可以穩(wěn)健和持久地模擬機(jī)械和熱敏感性變化,SN模型能真實(shí)再現(xiàn)許多神經(jīng)肽的臨床特征。

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Fig1. SNI surgery?induced neuropathic pain model. The SNI mouse model involves ligation of two of the three branches of the sciatic nerve (the tibial nerve and the common peroneal nerve), while the sural nerve is left intact . The lesion results in marked hypersensitivity in the lateral area of the paw, which is innervated by the spared sural nerve. Painful symptoms can last for months.


骨痛是癌癥患者最常見的疼痛類型之一。患者因骨轉(zhuǎn)移而經(jīng)歷的疼痛機(jī)制很復(fù)雜,它涉及腫瘤細(xì)胞、骨細(xì)胞、活化的炎癥細(xì)胞和骨神經(jīng)支配神經(jīng)元之間的各種相互作用。小鼠脛骨骨癌痛模型由于表型與患者臨床癥狀相似,疼痛檢測方法簡單等原因是目前十分理想的研究骨癌痛動(dòng)物模型,南模生物可提供多種腫瘤細(xì)胞(骨肉瘤細(xì)胞、乳腺癌細(xì)胞等)誘導(dǎo)的骨癌痛模型。

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Fig1. Idiopathic pain model induced by bone metastatic cancer. 231 cells were injected into the bone marrow cavity of the femur, and spontaneous pain and algesia could be observed in some of the mice 14 days after injection, and in almost all of the mice 21 days after injection. After treated some of the mice exhibiting pain with gabapentin for one week, there was a significant relief of spontaneous pain behaviour and algesia/hypersensitivity in the administered group of mice.


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