Jergova Stanislava, Huang Zhen, Lin Chi-Yen, Akamatsu Megumi, Sagen Jacqueline, Niu Li
The Miami Project, Miller School of Medicine, University of Miami, Miami, FL, USA.
Department of Chemistry, the Center for Neuroscience Research, University at Albany, SUNY, Albany, NY, USA.
Commun Biol. 2025 Sep 26;8(1):1375. doi: 10.1038/s42003-025-08772-8.
Spinal cord injury (SCI)-induced neuropathic pain remains difficult to treat. Given the high risk of using opioid analgesics as a primary treatment option, developing non-opioid therapeutic candidates is desirable. Studies in preclinical pain models have shown that antagonists of the ionotropic glutamate receptors (iGluRs) can inhibit pain without abuse potential. Here we report the first study of making and testing a group of RNA aptamers that inhibit iGluRs in a rat SCI pain model. Our results show that aptamers are efficacious in alleviating evoked and ongoing neuropathic symptoms in rats without any significant adverse effects. Furthermore, the antinociceptive efficacy of RNA aptamers on both tactile and cold hypersensitivity becomes steadily strengthened during repeated aptamer administrations and the antinociceptive protection persists for 2-3 extra weeks after the termination of intrathecal injection of aptamers. We also note potential sex differences in aptamer treatment, suggesting the possibility of tailoring the use of aptamers in sex-specific pain treatment. This study demonstrates that developing aptamers targeting iGluRs, especially kainate receptors, as potential analgesic candidates for treatment of SCI-induced pain, is promising.
脊髓损伤（SCI）所致的神经性疼痛仍然难以治疗。鉴于将阿片类镇痛药作为主要治疗选择存在高风险，开发非阿片类治疗候选药物是很有必要的。临床前疼痛模型研究表明，离子型谷氨酸受体（iGluRs）拮抗剂可抑制疼痛且无滥用可能性。在此，我们报告了第一项关于制备和测试一组能在大鼠SCI疼痛模型中抑制iGluRs的RNA适配体的研究。我们的结果表明，适配体在减轻大鼠诱发的和持续的神经性症状方面有效，且无任何显著不良反应。此外，在重复给予适配体期间，RNA适配体对触觉和冷超敏反应的镇痛效果会稳步增强，并且在鞘内注射适配体终止后，镇痛保护作用还会持续额外2至3周。我们还注意到适配体治疗中可能存在性别差异，这表明在针对性别的疼痛治疗中调整适配体的使用具有可能性。这项研究表明，开发靶向iGluRs，尤其是红藻氨酸受体的适配体作为治疗SCI所致疼痛的潜在镇痛候选药物是有前景的。
