LIPUS治疗慢性疼痛的研究进展
王恒1 王硕1 刘万涛（通讯作者）2

1甘肃医学院基础医学院人体解剖学教研室，甘肃平凉，744000；

2甘肃医学院临床医学院外科学教研室，甘肃平凉，744000；

摘要：慢性疼痛是指因组织损伤或者病理状况而产生的持久性疼痛感，其病理机理包含神经致敏，炎症持续以及组织修护受阻等多种因素的复杂交互影响。当下临床上常采用抗炎镇痛药物来医治慢性疼痛，阿片类药物和非甾体抗炎药就属于此类，不过这些药物常常会带来诸如胃肠道不适，睡眠障碍之类的严重影响健康的功能性副作用，从而制约了它们在临床上的全面推广，无创物理治疗手段在慢性疼痛治疗方面渐渐被人们所看重，光疗，声音疗法等就属于此类，超声疗法也是一种传统的无创物理刺激方法，在慢性疼痛治疗上慢慢表现出它的应用价值。低强度脉冲超声（Low-intensity pulsed ultrasound, LIPUS）以低强度传递，并以脉冲波形式输出，具有非热效应，仍然可以将声能传递给目标组织，给临床应用供应无创物理刺激，具有不会造成感染，不会损害组织，没有不良反应等优势，近些年，分子生物学，细胞力学以及医学成像技术不断发展，有关研究对于 LIPUS 镇痛机制的认知不再停留在宏观层面，而是逐步深入到细胞信号传导途径以及基因调控层次，这就为 LIPUS 在临床上的精确应用构筑了牢靠的理论根基，此综述尝试全面整理 LIPUS 治疗慢性疼痛涉及的机制及其临床应用的最新动态，进而为 LIPUS 的诊疗供应参照。

关键词：慢性疼痛；LIPUS；作用机制；临床应用

参考文献

[1]Xu M, Wang L,Wu S,et al.Review on experimental study and clinical application of low-intensity pulsed  ultrasound in inflammation[J].Quant Imaging Med Surg,2021,11(1):443-462.

[2]ter Haar G. Therapeutic applications of ultrasound[J].Prog Biophys Mol Biol,2007,93(1-3):111-129.

[3]Tanaka E,Kuroda S, Horiuchi S,et al.Low-intensity pulsed ultrasound in dentofacial tissue engineering[J].Ann Biomed Eng, 2015,43(4):871-886.

[4]Hong S,Kim J,Chung G,et al.Revolutionizing drug delivery:low-intensity pulsed ultrasound (LIPUS)-driven deep penetration into hypoxic tumor microenvironments of cholangiocarcinoma[J].Theranostics,2025,15(1):30-51.

[5]Li Y,Sun S,Li B,et al.Low-intensity pulsed ultrasound relieved the diabetic peripheral neuropathy in  mice via anti-oxidative stress mechanism[J].Ultrasonics,2025,150:107618.

[6]He M,Zhu H,Dong J,et al.Low-intensity pulsed ultrasound improves metabolic dysregulation in obese mice by suppressing inflammation and extracellular matrix remodeling[J].Ultrasonics,2025,145:107488.

[7]Lei H,Xin H,Guan R,et al.Low-intensity Pulsed Ultrasound Improves Erectile Function in Streptozotocin-induced Type I Diabetic Rats[J].Urology,2015,86(6):1211-1241.

[8]Du S, Liang C, Sun Y, et al. The Attenuating Effect of Low-Intensity Pulsed Ultrasound on Hypoxia-Induced Rat Chondrocyte Damage in TMJ Osteoarthritis Based on TMT Labeling Quantitative Proteomic Analysis[J].Front Pharmacol,2021,12:752734.

[9]Cheng K,Xia P,Lin Q,et al.Effects of low-intensity pulsed ultrasound on integrin-FAK-PI3K/Akt mechanochemical transduction in rabbit osteoarthritis chondrocytes[J].Ultrasound Med Biol, 2014,40(7):1609-1618.

[10]Liao Q, Chen J,Liu G. Low intensity pulsed ultrasound alleviates synovial fibrosis in osteoarthritis via the PI3K/AKT pathway[J].Sci Rep,2025,15(1):9644.

[11]Zhang B, Chen H, Ouyang J,et al.SQSTM1-dependent autophagic degradation of PKM2 inhibits the production of mature IL1B/IL-1β and contributes to LIPUS-mediated anti-inflammatory effect[J].Autophagy, 2020,16(7):1262-1278.

[12]Guo Y,Wang Y,Wang B, et al.Ultrasound-responsive renal-targeted nanoparticles deliver TAK-242 to inhibit  NF-κB/NLRP3 signaling and attenuate sepsis-associated acute kidney injury[J].Biomaterials, 2026,329:123922.

[13]Wu S,Zhou H,Ling H,et al.LIPUS regulates the progression of knee osteoarthritis in mice through primary cilia-mediated TRPV4 channels[J].Apoptosis,2024,29(5-6):785-798.

[14]Qin H,Luo Z,Sun Y,et al.Low-intensity pulsed ultrasound promotes skeletal muscle regeneration via modulating the inflammatory immune microenvironment[J].Int J Biol Sci, 2023,19(4):1123-1145.

[15]Yin J,Bao Y,Xu M, et al.Anti-inflammatory role of low-intensity pulsed ultrasound in inhibiting lipopolysaccharide-induced M1 polarization of RAW264.7 cells via Wnt2b/AXIN/β-catenin[J].PeerJ,2024,12:e18448.

[16]Yi W, Chen Q, Liu C, et al. LIPUS inhibits inflammation and catabolism through the NF-κB pathway in human  degenerative nucleus pulposus cells[J]. J Orthop Surg Res, 2021,16(1):619.

[17]Zhang X, Hu B, Sun J, et al. Inhibitory Effect of Low-Intensity Pulsed Ultrasound on the Expression of  Lipopolysaccharide-Induced Inflammatory Factors in U937 Cells[J]. J Ultrasound Med, 2017,36(12):2419-2429.

[18]Zhou J,Ning E, Lu L,et al.Effectiveness of low-intensity pulsed ultrasound on osteoarthritis:molecular  mechanism and tissue engineering[J].Front Med (Lausanne),2024,11:1292473.

[19]Liang C,Zhang Y, Yan Y,et al.LIPUS promotes osteogenic differentiation of rat BMSCs and osseointegration of dental implants by regulating ITGA11 and focal adhesion pathway[J].BMC Oral Health, 2025,25(1):22.

[20]Xiang M, Guo Q, Liu Y, et al. Low-intensity pulsed ultrasound enhances the osteogenic potential of PDLSCs-derived extracellular vesicles through COMP/PI3K/AKT[J].FASEB J,2025,39(1):e70299.

[21]Xu J, Chen C, Gan S, et al.Low-Intensity pulsed ultrasound enhances paracrine secretion of IGF and VEGF by  bmscs,promoting osteogenesis and angiogenesis[J]. BMC Musculoskelet Disord,2025,26(1):828.

[22]Han Y, Gao H, Gao J, et al. Low-intensity pulsed ultrasound regulates bone marrow mesenchymal stromal cells  differentiation and inhibits bone loss by activating the IL-11-Wnt/β-catenin  signaling pathway[J].Int Immunopharmacol, 2024,143(Pt 1):113380.

[23]Yu M,Bian Y,Wang L,et al.Low-intensity pulsed ultrasound enhances angiogenesis in rabbit capsule tissue  that acts as a novel vascular bed in vivo[J].Adv Clin Exp Med, 2021,30(6):581-589.

[24]Li X,Wang F,Zhang X, et al.Ultrasound-responsive piezoelectric analgesic microspheres alleviate osteoarthritis pain[J].J Control Release, 2025,385:114049.

[25]Li F, Gallego J, Tirko N N, et al. Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial  activation following intracortical microelectrode implantation[J]. Nat Commun, 2024,15(1):5512.

[26]Xu S,Gu L,Bao B,et al.Mechanistic insights into the neuroprotective effects of low-intensity transcranial ultrasound stimulation in post-cardiac arrest brain injury:Modulation of the Piezo1-Dkk3/PI3K-Akt pathway[J].Brain Behav Immun,2025,127:341-357.

[27]Zhao L, Feng Y, Shi A, et al. Neuroprotective Effect of Low-Intensity Pulsed Ultrasound Against MPP(+)-Induced  Neurotoxicity in PC12 Cells: Involvement of K2P Channels and Stretch-Activated  Ion Channels[J]. Ultrasound Med Biol,2017,43(9):1986-1999.

[28]Iacoponi F,Cafarelli A,Fontana F, et al. Optimal low-intensity pulsed ultrasound stimulation for promoting  anti-inflammatory effects in macrophages[J].APL Bioeng,2023,7(1):16114.

[29]Song M, Zhang M, He S,et al. Ultrasonic neuromodulation mediated by mechanosensitive ion channels: current and  future[J].Front Neurosci, 2023,17:1232308.

[30]Murthy S E,Loud M C, Daou I,et al.The mechanosensitive ion channel Piezo2 mediates sensitivity to mechanical pain  in mice[J].Sci Transl Med, 2018,10(462).

[31]Liu Y, Tian X, Chen L, et al. Low-intensity transcranial ultrasound stimulation and its regulatory effect on  pain[J]. Neuroscience, 2025,576:59-68.

[32]Liang D,Chen J,Zhou W, et al. Alleviation Effects and Mechanisms of Low-intensity Focused Ultrasound on Pain  Triggered by Soft Tissue Injury[J]. J Ultrasound Med, 2020,39(5):997-1005.

[33]Zhang J, Zhou H, Yang J, et al. Low-intensity pulsed ultrasound ameliorates depression-like behaviors in a rat  model of chronic unpredictable stress[J].CNS Neurosci Ther, 2021,27(2):233-243.

[34]Wang T,Ito A, Xu S, et al.Low-Intensity Pulsed Ultrasound Prompts Both Functional and Histologic Improvements While Upregulating the Brain-Derived Neurotrophic Factor Expression after Sciatic Crush Injury in Rats[J].Ultrasound Med Biol, 2021,47(6):1586-1595.

[35]Song W,Giannotti A,Bekiaridou A,et al.Low intensity trans-spinal focused ultrasound reduces mechanical sensitivity and suppresses spinal microglia activation in rats with chronic constriction injury[J].Bioelectron Med,2025,11(1):8.

[36]Lima Pessôa B,Hauwanga W N,Thomas A,et al.A Comprehensive Narrative Review of Neuropathic Pain:From Pathophysiology to Surgical Treatment[J].Cureus,2024,16(4):e58025.

[37]Pérez-Neri I,González-Aguilar A, Sandoval H,et al.Therapeutic Potential of Ultrasound Neuromodulation in Decreasing Neuropathic  Pain: Clinical and Experimental Evidence[J].Curr Neuropharmacol, 2021,19(3):334-348.

[38]Li M,Li L, Liu C,et al.Clinical efficacy of low-intensity pulsed ultrasound plus hormone therapy in patients with postherpetic neuralgia:An observational study[J].Pak J Med Sci, 2025,41(7):1899-1904.

[39]王琼,尚敬,夏威.低频超声治疗糖尿病患者周围神经病变性疼痛的疗效观察[J].中华物理医学与康复杂志, 2013,35(11).

[40]Hsieh Y,Lu Y,Yang N, et al. Methylcobalamin in Combination with Early Intervention of Low-Intensity Pulsed  Ultrasound Potentiates Nerve Regeneration and Functional Recovery in a Rat  Brachial Plexus Injury Model[J].Int J Mol Sci,2023,24(18).

[41]Zhao L,Feng Y,Hu H,et al.Low-Intensity Pulsed Ultrasound Enhances Nerve Growth Factor-Induced Neurite  Outgrowth through Mechanotransduction-Mediated ERK1/2-CREB-Trx-1 Signaling[J]. Ultrasound Med Biol, 2016,42(12):2914-2925.

[42]Ji W,Li M,Li L,et al. Effects of ultrasound of different intensities plus neurotrophic factors on inflammatory markers and oxidative stress, and clinical efficacy in patients with diabetic peripheral neuropathic pain[J].Pak J Med Sci,2025,41(9):2481-2485.

[43]Xia Z, Wang J, Wen X.Global assessment of pain care quality for musculoskeletal disorders:Insights from the quality of care index (QCI) from 1990 to 2021[J].PLoSOne,2025,20(10):e335235.

[44]Chen H, Wang Z,Zhang X, et al. Effects of low-intensity pulsed ultrasound on knee osteoarthritis: A systematic  review and meta-analysis of randomized controlled trials[J]. Clin Rehabil, 2022,36(9):1153-1169.

[45]Zhou X,Zhang X,Yu G,et al.Effects of Low-Intensity Pulsed Ultrasound on Knee Osteoarthritis:A Meta-Analysis of Randomized Clinical Trials[J].Biomed Res Int, 2018,2018:7469197.

[46]Acevedo-Gonzalez J C,Corpus-Gutierrez V, Angarita-Avendaño M, et al. "Percutaneous Ultrasound Treatment of Lumbar Facet Syndrome: A Systematic  Review."[J]. World Neurosurg, 2024,184:e317-e330.

[47]Tanveer F, Arslan S A, Darain H, et al. Effects of low-intensity pulsed ultrasound on pain and functional disability in  patients with early-stage lumbar spondylolysis: A randomized controlled trial[J]. J Bodyw Mov Ther, 2022,30:125-131.

[48]Ito A, Aoyama T, Yamaguchi S, et al. Low-intensity pulsed ultrasound inhibits messenger RNA expression of matrix  metalloproteinase-13 induced by interleukin-1β in chondrocytes in an  intensity-dependent manner[J]. Ultrasound Med Biol, 2012,38(10):1726-1733.

[49]Jaeger B. Myofascial trigger point pain[J]. Alpha Omegan, 2013,106(1-2):14-22.

[50]Qing W, Shi X, Zhang Q, et al. Effect of Therapeutic Ultrasound for Neck Pain: A Systematic Review and  Meta-Analysis[J]. Arch Phys Med Rehabil, 2021,102(11):2219-2230.

[51]Li X, Lin Y, He P, et al. Efficacy and safety of low-intensity ultrasound therapy for myofascial pain  syndrome: a systematic review and meta-analysis[J]. BMC Musculoskelet Disord, 2024,25(1):1059.

[52]Morya V K, Shahid H, Lang J, et al. Advancements in Therapeutic Approaches for Degenerative Tendinopathy: Evaluating  Efficacy and Challenges[J]. Int J Mol Sci, 2024,25(21).

[53]Hsu A R, Holmes G B. Preliminary Treatment of Achilles Tendinopathy Using Low-Intensity Pulsed  Ultrasound[J]. Foot Ankle Spec, 2016,9(1):52-57.

[54]Lai W C, Iglesias B C, Mark B J, et al. Low-Intensity Pulsed Ultrasound Augments Tendon, Ligament, and Bone-Soft Tissue  Healing in Preclinical Animal Models: A Systematic Review[J]. Arthroscopy, 2021,37(7):2318-2333.

[55]Pontari M, Giusto L. New developments in the diagnosis and treatment of chronic prostatitis/chronic  pelvic pain syndrome[J]. Curr Opin Urol, 2013,23(6):565-569.

[56]Zhou W, Du H, Wang Z, et al. Low-Intensity Pulsed Ultrasound Regulates Th17/Treg Balance With Potential  Association With the IL-1β/IL1R1/MyD88 Signaling Pathway to Alleviate Pelvic Pain  in a Rat Prostatitis Model[J]. Ultrasound Med Biol, 2026,52(2):451-461.

[57]Huang J, Liao Z, Zhao S, et al. Evaluation of a low-intensity pulsed ultrasound for chronic prostatitis type  IIIb/chronic pelvic pain syndrome: a randomized controlled trial[J]. Front Reprod Health, 2025,7:1714803.