DataSheet1_Distal neuropathic pain in HIV is associated with functional connectivity patterns in default mode and salience networks.docx

HIV-associated distal neuropathic pain (DNP) is one of the most prevalent, disabling, and treatment-resistant complications of HIV, but its biological underpinnings are incompletely understood. While data specific to mechanisms underlying HIV DNP are scarce, functional neuroimaging of chronic pain more broadly implicates the role of altered resting-state functional connectivity within and between salience network (SN) and default mode network (DMN) regions. However, it remains unclear the extent to which HIV DNP is associated with similar alterations in connectivity. The current study aimed to bridge this gap in the literature through examination of resting-state functional connectivity patterns within SN and DMN regions among people with HIV (PWH) with and without DNP. Resting state functional magnetic resonance imaging (rs-fMRI) scans were completed among 62 PWH with HIV-associated peripheral neuropathy, of whom 27 reported current DNP and 35 did not. Using subgrouping group iterative multiple estimation, we compared connectivity patterns in those with current DNP to those without. We observed weaker connectivity between the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) and stronger connectivity between the anterior cingulate cortex (ACC) and thalamus among those reporting DNP. Overall, these findings implicate altered within DMN (i.e., MPFC-PCC) and within SN (i.e., ACC-thalamus) connectivity as potential manifestations of adaptation to pain from neuropathy and/or mechanisms underlying the development/maintenance of DNP. Findings are discussed in the context of differential brain response to pain (i.e., mind wandering, pain aversion, pain facilitation/inhibition) and therapeutic implications.

人类免疫缺陷病毒相关远端神经病理性疼痛（HIV-associated distal neuropathic pain, DNP）是HIV感染最常见、致残率最高且治疗抵抗性最强的并发症之一，但其生物学机制尚未完全阐明。尽管针对HIV相关DNP发病机制的专项研究数据较为匮乏，但针对慢性疼痛的广泛性功能神经影像学研究提示，突显网络（salience network, SN）与默认模式网络（default mode network, DMN）的脑区内部及二者之间的静息态功能连接异常发挥了关键作用。然而目前仍不清楚，HIV相关DNP是否存在类似的连接异常以及其异常程度如何。本研究旨在填补这一研究空白，对合并与未合并远端神经病理性疼痛的HIV感染者（people with HIV, PWH）的SN及DMN脑区内部的静息态功能连接模式展开分析。本研究共纳入62例合并HIV相关周围神经病的HIV感染者，其中27例报告存在现症DNP，35例无相关症状，所有受试者均完成了静息态功能磁共振成像（resting-state functional magnetic resonance imaging, rs-fMRI）扫描。研究采用分组迭代多重估计算法（subgrouping group iterative multiple estimation），对比了现症DNP患者与非患者的脑连接模式。结果显示，合并现症DNP的感染者，其内侧前额叶皮层（medial prefrontal cortex, MPFC）与后扣带回皮层（posterior cingulate cortex, PCC）之间的连接强度显著减弱，而前扣带回皮层（anterior cingulate cortex, ACC）与丘脑之间的连接强度则显著增强。总体而言，本研究结果提示，默认模式网络内部（即MPFC-PCC通路）及突显网络内部（即ACC-丘脑通路）的功能连接异常，可能是神经病理性疼痛适应性改变的潜在表现，或是HIV相关DNP发生与维持的核心机制。本研究最后结合大脑对疼痛的差异化响应模式（即心智游移、疼痛厌恶、疼痛易化/抑制），讨论了本研究结果的科学意义与潜在治疗价值。