Neuropathic pain and cognitive impairment are among the HIV-related conditions that have most stubbornly resisted amelioration by virally suppressive antiretroviral therapy. Overlaps between the regional brain substrates and mechanisms of neuropathic pain and cognitive disorders are increasingly recognized, yet no studies have examined the longitudinal relationship between these two disorders. Participants in the prospective, observational CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort underwent standardized clinical evaluations for clinical examination findings of distal sensory polyneuropathy, reporting distal neuropathic pain and neurocognitive performance at study entry (baseline) and an average of 12 years later. Change in neuropathic pain and neuropathy status from baseline to follow-up was by self-report and repeat examination, and change in neurocognitive performance was assessed using a previously published summary regression-based change score. Relationships between incident or worsened neuropathic pain and neurocognitive change were evaluated using uni- and multivariable regressions, including age at baseline and other relevant covariates. Participants were 385 people with HIV, 91 (23.6%) females, mean ± standard deviation (SD) age at baseline 43.5 (7.81) years, ethnicity 44.9% African American, 10.6% Hispanic, 42.6% non-Hispanic white and 1.82% other. Baseline median (interquartile range) nadir CD4 was 175 (34 309) cells/µl and current CD4 was 454 (279 639). Incident or worsened distal neuropathic pain occurred in 98 (25.5%) over the follow-up period. People with HIV with incident or worsened distal neuropathic pain had significantly worsened neurocognitive performance at follow-up compared to those without incident or worsened distal neuropathic pain (summary regression-based change score mean ± SD -0.408 ± 0.700 versus -0.228 ± 0.613; P = 0.0158). This effect remained significant when considering viral suppression on antiretroviral therapy, incident diabetes and other covariates as predictors. Overall neurocognitive change related to neuropathic pain was driven primarily by changes in the domains of executive function and speed of information processing. Those with incident distal neuropathy signs did not have neurocognitive worsening, nor did individuals who used opioid analgesics or other pain-modulating drugs such as amitriptyline. Worsened neurocognitive performance in people with HIV was associated with worsened neuropathic pain but not with changes in physical signs of neuropathy, and this was not attributable to therapies for pain or depression or to differences in viral suppression. This finding implies that incident or worsened pain may signal increased risk for neurocognitive impairment, and deserves more investigation, particularly if better pain management might stabilize or improve neurocognitive performance.

中文翻译：

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神经性疼痛与人类免疫缺陷病毒感染者的认知恶化有关。

神经性疼痛和认知障碍是最顽固地抵抗病毒抑制性抗逆转录病毒疗法改善的 HIV 相关病症。区域脑底物与神经性疼痛和认知障碍的机制之间的重叠越来越被认可，但没有研究检查这两种疾病之间的纵向关系。前瞻性、观察性 CNS HIV 抗逆转录病毒治疗效果研究 (CHARTER) 队列的参与者接受了远端感觉性多发性神经病临床检查结果的标准化临床评估，报告了研究开始时（基线）和平均 12 年后的远端神经性疼痛和神经认知表现。从基线到随访的神经病理性疼痛和神经病变状态的变化是通过自我报告和重复检查进行的，神经认知表现的变化是使用先前发布的基于回归的总结变化评分来评估的。使用单变量和多变量回归评估事件或恶化的神经性疼痛与神经认知变化之间的关系，包括基线年龄和其他相关协变量。参与者为 385 名 HIV 感染者，其中 91 名 (23.6%) 为女性，基线时的平均±标准差 (SD) 年龄为 43.5 (7.81) 岁，种族为 44.9% 的非裔美国人、10.6% 的西班牙裔、42.6% 的非西班牙裔白人和 1.82% 的其他种族. 基线中位数（四分位数范围）最低点 CD4 为 175 (34 309) 个细胞/µl，当前 CD4 为 454 (279 639)。98 (25. 5%）在随访期间。与没有事件或恶化的远端神经性疼痛的人相比，患有事件性或恶化的远端神经性疼痛的 HIV 感染者在随访时的神经认知表现显着恶化（基于回归的汇总变化评分平均值±SD -0.408±0.700 对 -0.228±0.613；P = 0.0158）。当考虑抗逆转录病毒治疗的病毒抑制、糖尿病事件和其他协变量作为预测因子时，这种影响仍然很显着。与神经性疼痛相关的整体神经认知变化主要是由执行功能领域和信息处理速度的变化驱动的。那些出现远端神经病变体征的人没有神经认知恶化，使用阿片类镇痛药或其他镇痛药物（如阿米替林）的人也没有。HIV 感染者神经认知表现的恶化与神经性疼痛的恶化有关，但与神经病变的体征变化无关，这不能归因于疼痛或抑郁症的治疗或病毒抑制的差异。这一发现意味着疼痛事件或加重的疼痛可能预示着神经认知障碍的风险增加，值得更多研究，特别是如果更好的疼痛管理可能稳定或改善神经认知表现。