Yuan Su-Bo, Shi Yuqiang, Chen Jinghong, Zhou Xiangfu, Li Guangyu, Gelman Benjamin B, Lisinicchia Joshua G, Carlton Susan M, Ferguson Monique R, Tan Alai, Sarna Sushil K, Tang Shao-Jun
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX.
Ann Neurol. 2014 Jun;75(6):837-50. doi: 10.1002/ana.24139. Epub 2014 May 28.
Chronic pain is a common neurological comorbidity of human immunodeficiency virus (HIV)-1 infection, but the etiological cause remains elusive. The objective of this study was to identify the HIV-1 causal factor that critically contributes to the pathogenesis of HIV-associated pain.
We first compared the levels of HIV-1 proteins in postmortem tissues of the spinal cord dorsal horn (SDH) from HIV-1/acquired immunodeficiency syndrome patients who developed chronic pain (pain-positive HIV-1 patients) and HIV-1 patients who did not develop chronic pain (pain-negative HIV-1 patients). Then we used the HIV-1 protein that was specifically increased in the pain-positive patients to generate mouse models. Finally, we performed comparative analyses on the pathological changes in the models and the HIV-1 patients.
We found that HIV-1 gp120 was significantly higher in pain-positive HIV-1 patients (vs pain-negative HIV-1 patients). This finding suggested that gp120 was a potential causal factor of the HIV-associated pain. To test this hypothesis, we used a mouse model generated by intrathecal injection of gp120 and compared the pathologies of the model and the pain-positive human HIV-1 patients. The results showed that the mouse model and pain-positive human HIV-1 patients developed extensive similarities in their pathological phenotypes, including pain behaviors, peripheral neuropathy, glial reactivation, synapse degeneration, and aberrant activation of pain-related signaling pathways in the SDH.
Our findings suggest that gp120 may critically contribute to the pathogenesis of HIV-associated pain.
慢性疼痛是人类免疫缺陷病毒1型（HIV-1）感染常见的神经合并症，但其病因仍不清楚。本研究的目的是确定对HIV相关疼痛发病机制有关键作用的HIV-1致病因素。
我们首先比较了出现慢性疼痛的HIV-1/获得性免疫缺陷综合征患者（疼痛阳性HIV-1患者）和未出现慢性疼痛的HIV-1患者（疼痛阴性HIV-1患者）脊髓背角（SDH）尸检组织中HIV-1蛋白的水平。然后我们用在疼痛阳性患者中特异性升高的HIV-1蛋白建立小鼠模型。最后，我们对模型和HIV-1患者的病理变化进行了比较分析。
我们发现疼痛阳性HIV-1患者体内的HIV-1 gp120显著高于疼痛阴性HIV-1患者。这一发现表明gp120是HIV相关疼痛的潜在致病因素。为验证这一假设，我们使用鞘内注射gp120建立的小鼠模型，并比较了该模型与疼痛阳性人类HIV-1患者的病理情况。结果显示，小鼠模型与疼痛阳性人类HIV-1患者在病理表型上有广泛相似之处，包括疼痛行为、周围神经病变、胶质细胞活化、突触退化以及SDH中疼痛相关信号通路的异常激活。
我们的研究结果表明，gp120可能对HIV相关疼痛的发病机制起关键作用。
