Albany Medical College, Department of Anesthesiology, Albany, NY, USA.
Pain Physician. 2011 Nov-Dec;14(6):E505-24.
Human immunodeficiency virus (HIV)-related distal sensory polyneuropathy (DSP) is the most common HIV-associated sensory neuropathy. The envelope glycoprotein of HIV-1, gp 120, appears to contribute to this painful neuropathy. Two standard treatments for HIV infection/HIV-related painful DSP (e.g., antiviral therapy [e.g., nucleoside reverse transcriptase inhibitors (NRTI)] opioids) should each be carefully evaluated prior to being utilized to ameliorate the pain of DSP, since they may actually promote nociception. Nucleoside reverse transcriptase inhibitors require activation in the cell via the addition of 3 phosphate groups (by cellular kinases) to their deoxyribose moiety, to form NRTI triphosphates. Subsequently, these deoxynucleotide analogs compete with natural deoxynucleotides for incorporation into the growing viral DNA chain. The incorporation of NRTIs into the viral DNA chain leads to chain termination; since the nucleoside reverse transcriptase inhibitors lack a 3'-hydroxyl group on the deoxyribose moiety (unlike natural deoxynucleotides), so that the next incoming deoxynucleotide cannot form the next 5'-3' phosphodiester bond needed to extend the DNA chain. Unfortunately, many conventional agents utilized as pharmacologic therapy for neuropathic pain are not effective for providing satisfactory analgesia in painful HIV-related distal sensory polyneuropathy. Although there is no robust data, there does seem to be information which would support the notion of opioids having increased risk of being particularly pronociceptive when being used to treat painful HIV-related neuropathy. It thus appears conceivable that the use of at least certain opioids in efforts to achieve analgesia in patients with painful HIV-related neuropathy may be less than ideal since at least certain opioid analgesics themselves may potentially contribute to "fueling the fire" of HIV enhanced pain hypersensitivity; at least in part via upregulation of specific chemokine receptors (e.g., CXCR4) which seem to be vitally important in promoting HIV-related pain facilitation. The risk benefit ratio of treatment with agents such as NRTIs as well as opioids should be reviewed for specific individual patients, prior to clinicians initiating these agents.
To raise awareness of the theoretical potential downside that opioids may possess if they are used for the treatment of painful HIV-related neuropathy.
A narrative review of selected literature.
Hypothetical in nature.
Clinicians should consider all aspects of various therapeutic options, carefully weighing the risk/benefit ratios of each potential treatment before initiating opioids for painful HIV-related neuropathy.
人类免疫缺陷病毒（HIV）相关的远端感觉性多发性神经病（DSP）是最常见的与 HIV 相关的感觉性神经病。HIV-1 的包膜糖蛋白 gp120 似乎促成了这种疼痛性多发性神经病。两种标准的 HIV 感染/与 HIV 相关的疼痛性 DSP 治疗方法（例如抗病毒治疗[例如核苷逆转录酶抑制剂（NRTI）]阿片类药物）在用于改善 DSP 的疼痛之前，都应仔细评估，因为它们实际上可能促进伤害感受。NRTI 需要通过细胞激酶在细胞内将 3 个磷酸基团（3'磷酸基团）添加到其脱氧核糖部分，以形成 NRTI 三磷酸。随后，这些脱氧核苷酸类似物与天然脱氧核苷酸竞争掺入正在生长的病毒 DNA 链中。NRTI 掺入病毒 DNA 链会导致链终止；由于核苷逆转录酶抑制剂在脱氧核糖部分缺乏 3'-羟基（与天然脱氧核苷酸不同），因此下一个进入的脱氧核苷酸不能形成延伸 DNA 链所需的下一个 5'-3'磷酸二酯键。不幸的是，许多用于治疗神经性疼痛的常规药物在治疗疼痛性 HIV 相关的远端感觉性多发性神经病时并不能提供满意的镇痛效果。尽管没有强有力的数据，但似乎有信息支持这样的观点，即阿片类药物在治疗疼痛性 HIV 相关神经病时，其增加伤害感受的风险尤其大。因此，可以想象，在试图为患有疼痛性 HIV 相关神经病的患者实现镇痛时，至少某些阿片类药物的使用可能并不理想，因为至少某些阿片类镇痛药本身可能会潜在地导致“火上浇油”，增强 HIV 增强的疼痛敏感性；至少部分是通过上调特定趋化因子受体（例如 CXCR4），这些受体在促进 HIV 相关疼痛促进中似乎至关重要。在开始使用这些药物之前，临床医生应该针对特定的个体患者，对 NRTI 等药物治疗的风险效益比进行审查。
提高对阿片类药物如果用于治疗疼痛性 HIV 相关神经病可能存在的理论潜在负面影响的认识。
对选定文献进行叙述性综述。
假设性质。
临床医生在为疼痛性 HIV 相关神经病开始使用阿片类药物之前，应考虑各种治疗选择的各个方面，仔细权衡每种潜在治疗方法的风险/效益比。
