慢性疼痛药物靶点的研究进展

doi:10.3969/j.issn.1003-9198.2026.03.001

摘要/Abstract

摘要： 慢性疼痛是全球普遍存在且难以治愈的一种疾病,目前依赖的阿片类和非甾体抗炎药等治疗手段,由于存在不良反应或者疗效限制,无法满足临床医疗实践需求。本文对慢性疼痛药物靶点领域的研究动态进行全面综述。在传统靶点方面,阿片受体研究正聚焦于开发偏向性激动剂与优化个体化用药方案,环氧合酶靶点正朝着平衡调节与联合用药模式转变。另外,新兴靶点如离子通道、炎症介质以及神经递质受体的研究,为高特异性镇痛开辟了全新路径。但是,上述药物靶点的临床转化仍面临诸多挑战。另一方面,表观遗传调控、肠道菌群等前沿靶点结合人工智能技术,正在推动慢性疼痛精准医疗的发展。最后本文提出,目前仍存在物种差异、个体变异等研究障碍,未来的研究方向是开展多组学整合、多靶点药物研发,以制定更安全、有效且高度个体化的镇痛策略与疗法。

关键词: 慢性疼痛, 药物靶点, 阿片受体, 离子通道, 炎症因子

Abstract: Chronic pain is a globally prevalent and difficult-to-cure disease. Current treatment approaches, such as opioids and nonsteroidal anti-inflammatory drugs, are unable to meet the needs of clinical practice due to their adverse reactions and limited efficacy. This review comprehensively introduces the current research on drug targets for chronic pain. For traditional targets such as opioid receptors, the focus is now on developing biased agonists and optimizing personalized medication regimens, while cyclooxygenase targets are shifting towards balance regulation and using combination therapy. Emerging targets such as ion channels, inflammatory mediators, and neurotransmitter receptors is opening up new pathways for highly specific analgesia. However, it remains challenging to practical treatment. In addition, cutting-edge targets such as epigenetic regulation and gut microbiota, when combined with artificial intelligence technology, are driving the advancement of precision medicine for chronic pain. Finally, this paper points out that the current research still confronts challenges such as species differences and individual variations. Future research directions will focus on multi-omics integration and the development of multi-target drug, which may lead to the creation of safer, more effective, and highly personalized analgesic strategies and therapies.

Key words: chronic pain, drug target, opioid receptors, ion channel, inflammatory factor

中图分类号:

R 441.1

阿丽娜·扎瓦提拜, 但传才, 王赎, 吴征毅, 王昆, 朱威帆, 林青青, 刘焕兵. 慢性疼痛药物靶点的研究进展[J]. 实用老年医学, 2026, 40(3): 217-223.

Alina Zhawatibai, DAN Chuancai, WANG Shu, WU Zhengyi, WANG Kun, ZHU Weifan, LIN Qingqing, LIU Huanbing. Advances in drug targets for chronic pain[J]. Practical Geriatrics, 2026, 40(3): 217-223.

参考文献

[1] 刘延青, 崔健君. 实用疼痛学[M]. 北京: 人民卫生出版社, 2019: 1871.
[2] 徐建国. 成人手术后疼痛处理专家共识[J]. 临床麻醉学杂志, 2017, 33(9): 911-917.
[3] WOOD J N, YAN N, HUANG J, et al. Sensory neuron sodium channels as pain targets; from cocaine to Journavx (VX-548, suzetrigine)[J]. J Gen Physiol, 2025, 157(4): e202513778.
[4] AGULLÓ L, AGUADO I, MURIEL J, et al. Pharmacogenetic guided opioid therapy improves chronic pain outcomes and comorbid mental health: a randomized, double-blind, controlled study[J]. Int J Mol Sci, 2023, 24(13): 10754.
[5] 朱云柯, 林琳, 廖虎, 等. 中国胸外科围手术期疼痛管理专家共识(2018版)[J]. 中国胸心血管外科临床杂志, 2018, 25(11): 921-928.
[6] DEAL B, PHILLIPS K, CRELLI C, et al. RNA-seq reveals sex differences in gene expression during peripheral neuropathic inflammation and in pain relief from a COX-2 inhibiting theranostic nanoemulsion[J]. Int J Mol Sci, 2023, 24(11): 9163.
[7] BIRKINSHAW H, FRIEDRICH C, COLE P, et al. Antidepressants for pain management in adults with chronic pain: a network meta-analysis[J]. Health Technol Assess, 2024, 28(62): 1-155.
[8] KIM E, RAJI M A, WESTRA J, et al. Comparative effectiveness of pain control between opioids and gabapentinoids in older patients with chronic pain[J]. Pain,2024, 165(1): 144-152.
[9] FINNERUP N B, KUNER R, JENSEN T S. Neuropathic pain: from mechanisms to treatment[J]. Physiol Rev, 2021, 101(1): 259-301.
[10] JIANG W, ZHANG L X, TAN X Y, et al. Inflammation and histone modification in chronic pain[J]. Front Immunol,2023, 13: 1087648.
[11] XIONG H Y, HENDRIX J, SCHABRUN S, et al. The role of the brain-derived neurotrophic factor in chronic pain: links to central sensitization and neuroinflammation[J]. Biomolecules, 2024, 14(1): 71.
[12] CHEN L, JIANG J, DOU B, et al. Machine learning study of the extended drug-target interaction network informed by pain related voltage-gated sodium channels[J].Pain, 2023, 165(4): 908-921.
[13] TECHAMEENA P, FENG X, ZHANG K, et al. The single-cell transcriptomic atlas iPain identifies senescence of nociceptors as a therapeutical target for chronic pain treatment[J]. Nat Commun, 2024, 15(1):8585.
[14] XIN L, ZHU H, NIU S, et al. Pharmacodynamic characteristics and influencing factors of tapentadol for chronic pain relief under dose titration[J]. Front Pain Res: Lausanne, 2025, 5: 1474529.
[15] SECONDULFO C, MAZZEO F, PASTORINO G M G, et al. Opioid and cannabinoid systems in pain: emerging molecular mechanisms and use in clinical practice, health, and fitness[J]. Int J Mol Sci, 2024, 25(17): 9407.
[16] HAMEED M, PRASAD S, JAIN E, et al. Medical cannabis for chronic nonmalignant pain management[J]. Curr Pain Headache Rep, 2023, 27(4): 57-63.
[17] JO H G, BAEK C Y, HWANG Y, et al. Pain relief, functional recovery, and chondroprotective effects of Angelica gigas nakai in osteoarthritis due to its anti-inflammatory property: an in vitro and in vivo study[J]. Nutrients, 2024, 16(15): 2435.
[18] BOCCELLA S, DE FILIPPIS L, GIORGIO C, et al. Combination drug therapy for the management of chronic neuropathic pain[J]. Biomolecules, 2023, 13(12): 1802.
[19] CHENG P F, HE Y, GE M M, et al. Targeting the main sources of reactive oxygen species production: possible therapeutic implications in chronic pain[J]. Curr Neuropharmacol, 2024, 22(12): 1960-1985.
[20] BERTA T, STRONG J A, ZHANG J M, et al. Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain: an update[J]. Expert Opin Ther Targets, 2023, 27(8): 665-678.
[21] MCILWAIN B. A structural atlas for pain relief[J]. Nat Struct Mol Biol, 2023, 30(7): 873.
[22] ALSALOUM M, VASYLYEV D, WAXMAN S G. Targeting sodium channels - challenges for acute pain and the leap to chronic pain[J]. Nat Rev Neurol, 2025, 21(10): 567-576.
[23] YANG J, XIE Y F, SMITH R, et al. Discordance between preclinical and clinical testing of Na_V1.7-selective inhibitors for pain[J]. Pain, 2025, 166(3): 481-501.
[24] VARADI G. Mechanism of analgesia by gabapentinoid drugs: involvement of modulation of synaptogenesis and trafficking of glutamate-gated ion channels[J]. J Pharmacol Exp Ther, 2024, 388(1): 121-133.
[25] 李海婷, 吴小余, 曹春阳. 靶向酸敏感离子通道的毒素肽: 镇痛机制与生物合成开发[J]. 化学学报, 2025, 83(7): 755-772.
[26] SZALLASI A. Targeting TRPV1 for cancer pain relief: can it work?[J]. Cancers, 2024, 16(3): 648.
[27] WAN Y, ZHOU J, LI H. The role of mechanosensitive Piezo channels in chronic pain[J]. J Pain Res, 2024, 17: 4199-4212.
[28] MELANCON K, PLIUSHCHEUSKAYA P, MEILER J, et al. Targeting ion channels with ultra-large library screening for hit discovery[J]. Front Mol Neurosci,2024, 16: 1336004.
[29] KUETE C F, GRANJA-VAZQUEZ R, TRUONG V, et al. Profiling human iPSC-derived sensory neurons for analgesic drug screening using a multi-electrode array[J]. bioRxiv, 2024. DOI: 10.1101/2024.11.18.623405.
[30] DEY S, BHATTACHARYA T, SINHA S. Pain relief: unique derivatives of ibogaine alleviate both acute and chronic pain symptoms[J]. Physiology, 2024, 39(S1): 1689.
[31] XIA S, QIN X, WANG Y. DMH1-loaded peptide nanomicelles restore myelin and attenuate neuroinflammation in trigeminal neuralgiavia CCL5 suppression[J]. Front Pharmacol, 2025, 16: 1590624.
[32] BECKER J, EFFRAIM P R, DIB-HAJJ S, et al. Lessons learned in translating pain knowledge into practice[J]. Pain Rep, 2023, 8(6): e1100.
[33] JU J, LI Z, JIA X, et al. Interleukin-18 in chronic pain: focus on pathogenic mechanisms and potential therapeutic targets[J]. Pharmacol Res, 2024, 201: 107089.
[34] MORIOKA N. Drug developmental strategies based on functional analysis of pain-regulating molecules in astrocytes under chronic pain[J].Nihon Yakurigaku Zasshi, 2024, 159(6): 363-366.
[35] SOLIMAN N, KERSEBAUM D, LAWN T, et al. Improving neuropathic pain treatment - by rigorous stratification from bench to bedside[J]. J Neurochem,2024, 168(11): 3699-3714.
[36] MA L, SUN D, WEN S, et al. PSD-95 protein: a promising therapeutic target in chronic pain[J]. Mol Neurobiol,2025, 62(3): 3361-3375.
[37] CUI M, JI R, SONG L, et al. Neuronal and molecular mechanisms underlying chronic pain and depression comorbidity in the paraventricular thalamus[J]. J Neurosci, 2024, 44(13): e1752232024.
[38] RAJI M A, SHAH R, WESTRA J R, et al. Central nervous system active medication use in medicare enrollees receiving home health care: association with chronic pain and anxiety level[J]. Pain, 2025, 166(1): 123-129.
[39] 兰艳艳, 庞莉娜, 黄秋玲, 等. 基于脊髓背角5-HT_1AR途径探讨腕踝针治疗紫杉醇诱导神经性疼痛小鼠的镇痛机制[J]. 中华中医药杂志, 2025, 40(3): 1081-1085.
[40] 杜志强. 基于fMRI技术探讨温针治疗膝骨关节炎中枢镇痛机制的临床研究[C]//中国生命关怀协会. 关爱生命大讲堂之生命关怀与智慧康养系列学术研讨会论文集上-临床心理关怀与医院人文建设的融合专题. 北京, 2025: 500-502.
[41] JI R R, CHAMESSIAN A, ZHANG Y Q. Pain regulation by non-neuronal cells and inflammation[J]. Science, 2016, 354(6312): 572-577.
[42] JI R R, XU Z Z, GAO Y J. Emerging targets in neuroinflammation-driven chronic pain[J]. Nat Rev Drug Discov, 2014, 13(7): 533-548.
[43] CHIU I M. Infection, pain, and itch[J]. Neurosci Bull, 2018, 34(1): 109-119.
[44] GRACE P M, HUTCHINSON M R, MAIER S F,et al. Pathological pain and the neuroimmune interface[J]. Nat Rev Immunol, 2014, 14(4): 217-231.
[45] MURPHY S F, SCHAEFFER A J, THUMBIKAT P. Immune mediators of chronic pelvic pain syndrome[J]. Nat Rev Urol, 2014, 11(5): 259-269.
[46] TSUDA M. Modulation of pain and itch by spinal glia[J]. Neurosci Bull, 2018, 34(1): 178-185.
[47] DO NASCIMENTO A M, MARQUES R B, ROLDÃO A P, et al. Exploring protein-protein interactions for the development of new analgesics[J]. Sci Signal, 2024, 17(857): eadn4694.
[48] QU X, DU G, HU J, et al. Graph-DTI: a new model for drug-target interaction prediction based on heterogenous network graph embedding[J]. Curr Comput Aided Drug Des, 2024, 20(6): 1013-1024.
[49] MOHAPATRA M, SAHU C, MOHAPATRA S. Trends of artificial intelligence (AI) use in drug targets, discovery and development: current status and future perspectives[J]. Curr Drug Targets, 2025, 26(4): 221-242.
[50] MOHANKUMAR N, REDDY NARANI S, ASHA S, et al. Advancing chronic pain relief cloud-based remote management with machine learning in healthcare[J]. Indones J Electr Eng Comput Sci, 2025, 37(2): 1042-1052.
[51] MEIER T A, REFAHI M S, HEARNE G, et al. The role and applications of artificial intelligence in the treatment of chronic pain[J]. Curr Pain Headache Rep, 2024, 28(8): 769-784.