Characterization of a mouse neuropathic pain model caused by the highly active antiviral therapy (HAART) Stavudine.
Characterization of a mouse neuropathic pain model caused by the highly active antiviral therapy (HAART) Stavudine.
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由高活性抗病毒疗法（HAART）司他夫定引起的小鼠神经性疼痛模型的表征。
DOI：
10.1007/s43440-021-00262-y
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
McMahon,LanceR
中科院分区：
文献类型：
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作者：
Wilkerson,JennyL;Felix,JasmineS;Bilbrey,JoshuaA;McCurdy,ChristopherR;McMahon,LanceR
尽管高效抗病毒治疗（HAART）对获得性免疫缺陷综合征（AIDS）患者的病毒复制施加控制，但神经性疼痛是副作用。症状包括痛觉过敏和异常性疼痛。司他夫定，也称为D4 T，是一种用于治疗人类免疫缺陷病毒（HIV）的HAART。本研究在何种程度上D4 T产生神经性疼痛和检查药理学管理与一个标准的阿片类镇痛剂。MethodsMale和female C57 BL/6 J小鼠腹腔注射一个剂量的车辆或D4 T（10-56毫克/公斤）。在注射后第92天测试小鼠的机械异常性疼痛（用von Frey细丝评估）和热痛觉过敏（通过热板测试评估）。单独的队列接受车辆或56 mg/kg的D4 T，异常性疼痛和热痛觉过敏的存在下确认，和小鼠接受腹腔内的车辆，吗啡，或0.032 mg/kg的纳洛酮+ morphine.ResultsD4T产生剂量和时间依赖性的机械异常性疼痛和热痛觉过敏。最小有效D4 T剂量为17.8 mg/kg。该剂量产生机械异常性疼痛，但不产生热痛觉过敏。较大的D4 T剂量（32和56 mg/kg）产生持续92天的机械异常性疼痛和热痛觉过敏。吗啡剂量依赖性地减轻D4 T处理的小鼠的机械异常性疼痛和热痛觉过敏，ED 50值分别为4.4和1.2 mg/kg。纳洛酮使吗啡剂量-反应函数发生了显著性变化，即，增加ED 50值吗啡至少3.8倍。结论司他夫定产生神经病理性疼痛作为剂量和时间的函数在小鼠。阿片类镇痛剂似乎在D4 T诱导的小鼠模型中有效缓解神经性疼痛。
BackgroundAlthough highly active antiviral therapies (HAART) exert control over viral replication in persons with Acquired Immunodeficiency Syndrome (AIDS), neuropathic pain is a side effect. Symptoms include hyperalgesia and allodynia. Stavudine, also known as D4T, is a HAART used to treat Human Immunodeficiency Virus (HIV). This study examined the extent to which D4T produces neuropathic pain and examined pharmacological management with a standard opioid analgesic.MethodsMale and female C57BL/6 J mice were injected intraperitoneally with one dose of vehicle or D4T (10–56 mg/kg). Mice were tested through day 92 post injection for mechanical allodynia, assessed with von Frey filaments, and thermal hyperalgesia, assessed via the hotplate test. Separate cohorts received vehicle or 56 mg/kg D4T, the presence of allodynia and thermal hyperalgesia confirmed, and mice received intraperitoneal vehicle, morphine, or 0.032 mg/kg naltrexone + morphine.ResultsD4T produced dose- and time-dependent mechanical allodynia and thermal hyperalgesia. The smallest effective D4T dose was 17.8 mg/kg. This dose produced mechanical allodynia but not thermal hyperalgesia. Larger D4T doses (32 and 56 mg/kg) produced mechanical allodynia and thermal hyperalgesia lasting 92 days. Morphine dose-dependently alleviated both mechanical allodynia and thermal hyperalgesia in D4T-treated mice with ED50 values of 4.4 and 1.2 mg/kg, respectively. Naltrexone produced a rightward shift of the morphine dose–response function, i.e., increased the ED50 value of morphine by at least 3.8-fold.ConclusionStavudine produced neuropathic pain as a function of dose and time in mice. Opioid analgesics appear to be effective in alleviating neuropathic pain in a D4T-induced mouse model.