Low-intensity Pulsed Ultrasound Group Research Articles

BMSCs transplantation combined with LIPUS treatment improves erectile function through downregulation of IGFBP3 in rats with cavernosa injury.

Erectile dysfunction (ED) is the most common type of sexual dysfunction, which seriously affects male reproductive health. Recently, stem cell therapy and low-intensity pulsed ultrasound (LIPUS) have been applied in the treatment of ED, but the specific mechanism is still unclear. The study aims to investigate the effect and underlying mechanism of further LIPUS treatment on the basis of bone marrow mesenchymal stem cells (BMSCs) transplantation in the treatment of ED rats. We established a cavernosa injury-induced ED rat model and injected BMSCs into the penile corpus cavernosum with or without LIPUS treatment every other day for three times. The survival rate of BMSCs, value of ICP/MAP, blood flow, the endothelial content, and expression of CD31 and ɑ-SMA in the rat penis were investigated. Transcriptome analyses and in vitro assays of cell proliferation, migration, and tube formation were also performed. The results showed that LIPUS treatment significantly promoted the survival rate of BMSCs in the rat penis after 1, 7, and 14 days of final treatment. The values of ICP/MAP and blood flow in rats treated with BMSCs were significantly increased compared to the control group, and the values were further enhanced in rats treated with BMSCs plus LIPUS. The endothelial content and CD31 and ɑ-SMA mRNA and protein expression in the BMSCs plus LIPUS group were remarkably higher than in other groups, indicating improved endothelial vascular function. Transcriptome analyses found that insulin-like growth factor binding protein-3 (IGFBP3) was remarkably downregulated in the BMSCs plus LIPUS group compared to the other two groups. In in vitro assays, LIPUS intervention significantly increased BMSCs proliferation and HUVECs migration, and HUVECs angiogenesis was improved after IGFBP3 siRNA transfection. BMSCs transplantation combined with LIPUS treatment could improve erectile function in ED rats via downregulation of IGFBP3, which might be a proposed optimized strategy for the ED treatment.

Evaluation of efficacy and safety of low-intensity pulsed ultrasound in patients with concurrent erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome: a prospective, randomized controlled study

ObjectiveThe primary objective of this clinical trial is to investigate the effect of low-intensity pulsed ultrasound (LIPUS) on patients suffering from comorbid erectile dysfunction (ED) and chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS).MethodsThe clinical trial was conducted in the andrology outpatient treatment room of the Department of Urology, Xiangya Hospital, Central South University from August to November 2022 A total of 60 patients who met the research criteria for comorbid ED combined with CP/CPPS were recruited and randomly assigned to three treatment groups. They were treated with LIPUS (Group A), drug therapy(Group B), and LIPUS combined with drug therapy (Group C), respectively. Each group comprised 20 patients. Statistical analysis was performed on the five-item version of International Index of Erectile Function (IIEF-5), Erection Hardness Score (EHS), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the nine-item Patient Health Questionnaire (PHQ-9), the seven-item Generalized Anxiety Disorder Scale (GAD-7), and the incidence of adverse events to comprehensively evaluate the efficacy and safety of LIPUS.ResultsThe positive response rate of ED and CP/CPPS treatment in Group A is 40%(8/20) and 45%(9/20), while those in Group B is 55%(11/20) and 60%(12/20), and those in Group C is 85%(17/20) and 85%(17/20). A notable increase in IIEF-5 scores was observed across the three groups post-treatment (10.45 ± 2.50 vs. 13.65 ± 3.03, P = 0.008; 11.80 ± 3.21 vs. 16.40 ± 3.20, P = 0.011; 12.90 ± 3.92 vs. 19.40 ± 2.35, P = 0.042) with a concomitant significant decrease in NIH-CPSI scores (16.75 ± 4.53 vs. 14.65 ± 4.51, P = 0.016; 16.35 ± 4.32 vs. 12.20 ± 4.74, P = 0.007; 16.00 ± 4.40 vs. 8.15 ± 4.28, P = 0.021). Notably, the most pronounced changes were seen in the group receiving LIPUS combined with tadalafil and doxazosin. Additionally, all groups exhibited marked improvements in anxiety and depression symptoms post-treatment. No adverse events were observed during treatment.ConclusionLIPUS can improve erectile function and CP/CPPS symptoms with good safety, and LIPUS combined with tadalafil and doxazosin is more effective during the treatment. However, its long-term efficacy remains to be seen.Trial RegistrationChinese Clinical Trial Registry; approval number: ChiCTR2200063038 (https://www.chictr.org.cn/) on August 29, 2022.

Clinical efficacy of low-intensity pulsed ultrasound in Parkinson's disease with cognitive impairment.

Low-intensity pulsed ultrasound (LIPUS) is a new technique for invasive brain stimulation and modulation that has emerged recently, but the effects in Parkinson's disease with cognitive impairment (PD-CI) have been less observed. In this study, we recruited 56 patients with PD-CI who were continuously treated with LIPUS for 8 wk, and observed the clinical efficacy of LIPUS on patients with PD-CI by comparing with the Sham stimulation continuous treatment. Fifty-six patients with PD-CI were divided into the Sham group (given Sham stimulation on top of conventional medication, n = 28) and the LIPUS group (given LIPUS stimulation on top of conventional medication, n = 28), and both groups continued treatment for 8 wk. Post-treatment efficacy and pre- and post-treatment cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA)], emotional state [Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI)], quality of life [Unified Parkinson's Disease Rating Scale (UPDRS), 39-item Parkinson's Disease Questionnaire (PDQ-39)], and serologic indices [5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA)] were compared. The total effective rate of the LIPUS group was higher versus that of the Sham group. In both groups, MMSE and MoCA scores increased; BDI and BAI scores decreased; UPDRS and PDQ-39 scores were reduced; the levels of 5-HT, NE, and DA were elevated. The aforementioned changes were more pronounced in the LIPUS group (all P < 0.05). The application of LIPUS on PD-CI could ameliorate patients' cognitive function, emotional state, and quality of life, and regulate and optimize neurotransmitter expression levels.NEW & NOTEWORTHY This paper provides some data to inform the potential of LIPUS in the treatment of PD-CI.

3D-Cultured MC3T3-E1-Derived Exosomes Promote Endothelial Cell Biological Function under the Effect of LIPUS.

Porous Ti-6Al-4V scaffold materials can be used to heal massive bone defects because they can provide space for vascularisation and bone formation. During new bone tissue development, rapid vascular ingrowth into scaffold materials is very important. Osteoblast-derived exosomes are capable of facilitating angiogenesis-osteogenesis coupling. Low-intensity pulsed ultrasound (LIPUS) is a physical therapy modality widely utilised in the field of bone regeneration and has been proven to enhance the production and functionality of exosomes on two-dimensional surfaces. The impact of LIPUS on exosomes derived from osteoblasts cultured in three dimensions remains to be elucidated. In this study, exosomes produced by osteoblasts on porous Ti-6Al-4V scaffold materials under LIPUS and non-ultrasound stimulated conditions were co-cultured with endothelial cells. The findings indicated that the exosomes were consistently and stably taken up by the endothelial cells. Compared to the non-ultrasound group, the LIPUS group facilitated endothelial cell proliferation and angiogenesis. After 24 h of co-culture, the migration ability of endothelial cells in the LIPUS group was 17.30% higher relative to the non-ultrasound group. LIPUS may represent a potentially viable strategy to promote the efficacy of osteoblast-derived exosomes to enhance the angiogenesis of porous Ti-6Al-4V scaffold materials.

Therapeutic effects of LIPUS on the elasticity of injured tendons: animal experiment

Abstract This paper aims to explore the efficacy and duration of low-intensity pulsed ultrasound (LIPUS) treatment in improving the elastic properties of injured tendons through animal experiments. 48 healthy 3-month-old New Zealand white rabbits (weight 2.5-3.0 kg) were randomly divided into the Control group (n = 9) and model group (n = 39). The rabbits in the model group were injected with 0.2ml PGE2 mixed solution (concentration: 500 ng/0.2ml) into the Achilles tendon 2cm above the calcaneus, once a week, for 4 weeks, to build the Achilles tendon injury model. The Control group was injected with the same volume of PBS solution. Three rabbits were randomly selected from the Control and model groups for model validation, the model group was randomly divided into the Model (n = 6) and LIPUS (n = 30) groups. Then the LIPUS was randomly divided into the LIPUS1 (n = 6), LIPUS4 (n = 6), LIPUS7 (n = 6), LIPUS14 (n = 6), and LIPUS28 (n = 6) subgroups. Following interventions on days 1, 4, 7, 14, and 28, tendon elasticity was assessed by shear wave elastography (SWE). The elastic modulus of the Model, LIPUS1, and LIPUS4 groups exhibited a significant decrease compared to the Control group during the early stages of treatment. With prolonged treatment duration, the elastic modulus of LIPUS groups gradually increased. By day 7, no statistically significant difference in elastic modulus existed between the LIPUS7 and Control groups, indicating that LIPUS treatment had successfully restored the Achilles tendon’s elasticity to a healthy state. In summary, LIPUS therapy demonstrates the potential to effectively ameliorate the elastic properties of injured Achilles tendons.

Study on the Effects of Low-Intensity Pulsed Ultrasound and Iron Ions for Proliferation and Differentiation of Osteoblasts

ObjectiveThis study involved the proliferation and differentiation of osteoblasts treated with low-intensity pulsed ultrasound (LIPUS) and iron (Fe3+) ions, respectively. The biological effects of LIPUS and Fe3+ ions on the proliferation and differentiation of osteoblasts were also evaluated. MethodsMC3T3-E1 cells were seeded in six-well plates with the medium, which contained different concentrations of Fe3+ (0, 100, 200, 300, 400, 500, 600 and 700 μg L-1, respectively). LIPUS treatment was directed at the bottom of the plate for 20 min at an intensity of 80 mW cm-2 every day. ResultsViability results showed that a dose of 400 μg L-1 Fe3+ ions had the best effect at promoting osteogenic proliferation in cell culture. The results of alkaline phosphatase staining and mineralization indicated that the differentiation of osteoblasts was promoted by LIPUS and Fe3+ ions. Fluorescence staining results showed that the number of cell nuclei in the LIPUS, Fe3+ and LIPUS-Fe groups increased by 37.20%, 55.81% and 89.76%, respectively. Migration data indicated that migration and proliferation rates were increased by LIPUS and Fe3+, and the results of protein expression indicated that LIPUS and Fe3+ may increase the expression of Wnt, β-catenin, and Runx2, hence promoting normal bone regeneration and development. ConclusionThe combination of LIPUS (1.5 MHz, 80 mW cm-2) and Fe3+ accelerates the proliferation and differentiation of osteoblasts significantly compared with single-factor treatment (stimulated by LIPUS and Fe3+ ions, respectively). This study could establish a foundation for LIPUS-responsive biomaterials in the repair and regeneration of bone tissues.

Enhanced antibiofilm potential of low-intensity pulsed ultrasound combined with 0.35% povidone-iodine in a rat model of periprosthetic joint infection.

Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI). A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR. The group with LIPUS and 0.35% PI exhibited decreased levels of serum biochemical markers, improved weightbearing scores, reduced reactive bone changes, absence of viable bacteria, and decreased inflammation compared to the Control group. Despite the greater antibiofilm activity observed in the PI group compared to the LIPUS and saline group, none of the monotherapies were successful in preventing reactive bone changes or eliminating the infection. In the rat model of PJI treated with DAIR, LIPUS combined with 0.35% PI demonstrated stronger antibiofilm potential than monotherapy, without impairing any local soft-tissue.

Low-Intensity Pulsed Ultrasound Versus Sham in the Treatment of Operatively Managed Scaphoid Nonunions: The SNAPU Randomized Controlled Trial.

This article was updated on September 4, 2024 because of a previous error, which was discovered after the preliminary version of the article was posted online. In the Note listing the members of the Wrist and Elbow Research Group of Canada, the text that had read "Thomas T. Goetz, MD, FRCSC" now reads "Thomas J. Goetz, MD, FRCSC". The primary goal after open reduction and internal fixation of an established scaphoid nonunion is to achieve union. Low-intensity pulsed ultrasound (LIPUS) has been reported to increase the rate of union and to decrease the time to union for multiple fractures and nonunions in clinical and animal models. The evidence for LIPUS in the treatment of scaphoid nonunion, however, is sparse. The aim of this study was to assess whether active LIPUS (relative to sham LIPUS) accelerates the time to union following surgery for scaphoid nonunion. Adults with a scaphoid nonunion indicated for surgery were recruited for a multicenter, prospective, double-blinded randomized controlled trial. After surgery, patients self-administered activated or sham LIPUS units beginning at their first postoperative visit. The primary outcome was the time to union on serial computed tomography (CT) scans starting 6 to 8 weeks postoperatively. Secondary outcomes included patient-reported outcome measures, range of motion, and grip strength. A total of 142 subjects completed the study (69 in the active LIPUS group and 73 in the sham group). The average age was 27 years, and the cohort was 88% male. There was no difference in time to union (p = 0.854; hazard ratio, 0.965; 95% confidence interval, 0.663 to 1.405). Likewise, there were no differences between the active LIPUS and sham groups with respect to any of the secondary outcomes, except for wrist flexion at baseline (p = 0.008) and at final follow-up (p = 0.043). Treatment with LIPUS had no effect on reducing time to union in patients who underwent surgical fixation of established scaphoid nonunions. Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Low-intensity pulsed ultrasound combined with ST36 modulate gastric smooth muscle contractile marker expression via RhoA/Rock and MALAT1/miR-449a/DLL1 signaling in diabetic rats.

Low-intensity pulsed ultrasound (LIPUS) combined with acupoint can promote gastric motility of diabetic rats. The switch of gastric smooth muscle cell (GSMCs) phenotype was related to the diabetes-induced gastric dysfunction, but the mechanism is not clearly elucidated. This study was aimed at exploring the underlying mechanism of LIPUS stimulation application in diabetic gastroparesis rats. In this study, Sprague-Dawley male rats were divided into three groups: control group (CON), diabetic gastroparesis group (DGP), and LIPUS-treated group (LIPUS). LIPUS irradiation was performed bilaterally at ST36 for 20 min per day for 4 weeks. The gastric emptying rate was measured by ultrasound examination. Contraction ability of GSMCs was assessed by muscle strip experiment. The expression of related proteins or mRNAs including α-SMA, SM22α, MHC, RhoA, Rock2, p-MYPT1, MYPT1, p-MLC, MLC, MALAT1, miR-449a, and DLL1 was detected by different methods such as western blotting, RT-qPCR, immunohistochemistry, and immunofluorescence staining, as appropriate. (a) LIPUS stimulation at ST36 could improve the gastric motility dysfunction of diabetic rats. (b) LIPUS increased RhoA, Rock2, p-MYPT1, and p-MLC expression level. (c) MALAT1 and DLL1 contents were decreased, but the level of miR-449a was increased in the LIPUS group. LIPUS may affect the contractile marker expression of gastric smooth muscle through the RhoA/Rock and MALAT1/miR-449a/DLL1 pathway to ameliorate DGP.

The value of low-intensity pulsed ultrasound in reducing ovarian injury caused by chemotherapy in mice

BackgroundOvarian damage and follicle loss are major side effects of chemotherapy in young female patients with cancer. However, effective strategies to prevent these injuries are still lacking. The purpose of this study was to verify low-intensity pulsed ultrasound (LIPUS) can reduce ovarian injury caused by chemotherapy and to explore its underlying mechanisms in mice model.MethodsThe mice were randomly divided into the Control group, Cisplatin group, and Cisplatin + LIPUS group. The Cisplatin group and Cisplatin + LIPUS group were intraperitoneally injected with cisplatin every other day for a total of 10 injections, and the Control group was injected with saline. On the second day of each injection, the Cisplatin + LIPUS group received irradiation, whereas the other two groups received sham irradiation. We used a variety of biotechnologies to detect the differences in follicle count, granulosa cell apoptosis, fibrosis, transcriptome level, oxidative damage, and inflammation in differently treated mice.ResultLIPUS was able to reduce primordial follicle pool depletion induced by cisplatin and inhibit the apoptosis of granulosa cells. Transcriptomic results confirmed that LIPUS can reduce ovarian tissue injury. We demonstrated that LIPUS can relieve ovarian fibrosis by inhibiting TGF-β1/Smads pathway. Meanwhile, it can reduce the oxidative damage and reduced the mRNA levels of proinflammatory cytokines caused by chemotherapy.ConclusionLIPUS can reduce the toxic effects of chemotherapy drugs on ovaries, inhibit ovarian fibrosis, reduce the inflammatory response, and redcue the oxidative damage, reduce follicle depletion and to maintain the number of follicle pools.

Efficacy of Wearable low-intensity pulsed Ultrasound treatment in the Movement disorder in Parkinson’s disease (the SWUMP trial): protocol for a single-site, double-blind, randomized controlled trial

BackgroundParkinson’s disease (PD) is a progressive, neurodegenerative illness marked by the loss of dopaminergic neurons, causing motor symptoms. Oral levodopa replacement therapy remains the gold standard in the treatment of PD. It is, nevertheless, a symptomatic treatment. There is currently no effective treatment for PD. Therefore, new therapies for PD are highly desirable. Low-intensity pulsed ultrasound (LIPUS) has been shown to improve behavioral functions in PD animal models. It is a new type of neuromodulation approach that combines noninvasiveness with high spatial precision. The purpose of this study is to establish a new clinical protocol for LIPUS in the treatment of movement disorders in patients with PD.MethodsThis protocol is a single-site, prospective, double-blind, randomized controlled trial (RCT). Forty-eight participants with clinically confirmed PD will be randomly allocated to one of two groups: LIPUS group or sham group. All of the participants continue to use pharmacological therapy as a fundamental treatment. The primary outcome is the difference between groups from baseline to 4 months in the change in the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score (part III). The secondary outcomes include the rating scales such as the Mini-Mental State Examination (MMSE), and other three rating scales, and medical examinations including high-density electroencephalography (hdEEG) and functional magnetic resonance imaging (fMRI). The primary safety outcome will be assessed at 4 months, and adverse events will be recorded.DiscussionThis study represents the clinical investigation into the efficacy of therapeutic LIPUS in the treatment of PD for the first time. If LIPUS is determined to be effective, it could offer a practical and innovative means of expanding the accessibility of ultrasound therapy by using a wearable LIPUS device within a home setting.Trial registrationChinese Clinical Trial Registry ChiCTR2100052093. Registered on 17 October 2021.

The Effect of Low-Intensity Pulsed Ultrasound on Temporomandibular Joint Arthritis in Juvenile Rats.

Juvenile idiopathic arthritis is an inflammatory disease that can affect the temporomandibular joint (TMJ) and lower jaw growth. Better treatment options are needed, so this study investigated the effect of low-intensity pulsed ultrasound (LIPUS) on TMJ arthritis. Seventy-two 3-week-old male Wistar rats were invivo microcomputed tomography (micro-CT) scanned and divided into eight groups (n = 9). These groups were Group 1-TMJ arthritis and immediate LIPUS treatment (20 min/day, 4 weeks); Group 2-immediate LIPUS treatment and no TMJ arthritis; Group 3-TMJ arthritis and no LIPUS; Group 4-no TMJ arthritis and no LIPUS; Group 5-TMJ arthritis and LIPUS treatment with a delayed start by 4 weeks; Group 6-Delayed LIPUS and no TMJ arthritis; Group 7-TMJ arthritis and no (delayed) LIPUS; and Group 8-no TMJ arthritis and no (delayed) LIPUS. Ex vivo micro-CT scanning was completed, and samples were prepared for tissue analysis. Synovitis was observed in the TMJ arthritis (collagen-induced arthritis [CIA]) groups, but the severity appeared greater in the groups without LIPUS treatment. Fibrocartilage and hypertrophic cell layer thicknesses in the CIA group without LIPUS treatment were significantly greater (p < 0.05). Proteoglycan staining appeared greater in the LIPUS groups. Immediate LIPUS treatment increased the expression of type II collagen, type X collagen, and transforming growth factor-beta 1 (TGF-β1) immunostaining, and CIA (no LIPUS) increased MMP-13, vascular endothelial growth factor, and interleukin-1 beta (IL-1β) immunostaining. LIPUS treatment prevented growth disturbances observed in the CIA groups (no LIPUS) (p < 0.005). Our results have contributed to the understanding of the uses and limitations of the CIA juvenile rat model and have demonstrated the effects of LIPUS on the TMJ and mandibular growth. This information will help in designing future studies for investigating LIPUS and TMJ arthritis, leading to the development of new treatment options for children with juvenile arthritis in their TMJs.

The Effect of Low-Intensity Pulsed Ultrasound on Bone Regeneration and the Expression of Osterix and Cyclooxygenase-2 during Critical-Size Bone Defect Repair.

Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound that utilizes low-intensity pulsed waves. Its effect on bones that heal by intramembranous ossification has not been sufficiently investigated. In this study, we examined LIPUS and the autologous bone, to determine their effect on the healing of the critical-size bone defect (CSBD) of the rat calvaria. The bone samples underwent histological, histomorphometric and immunohistochemical analyses. Both LIPUS and autologous bone promoted osteogenesis, leading to almost complete closure of the bone defect. On day 30, the bone volume was the highest in the autologous bone group (20.35%), followed by the LIPUS group (19.12%), and the lowest value was in the control group (5.11%). The autologous bone group exhibited the highest intensities of COX-2 (167.7 ± 1.1) and Osx (177.1 ± 0.9) expression on day 30. In the LIPUS group, the highest intensity of COX-2 expression was found on day 7 (169.7 ±1.6) and day 15 (92.7 ± 2.2), while the highest Osx expression was on day 7 (131.9 ± 0.9). In conclusion, this study suggests that LIPUS could represent a viable alternative to autologous bone grafts in repairing bone defects that are ossified by intramembranous ossification.

The effectiveness of low-level laser therapy and low-intensity pulsed ultrasound in reducing pain induced by orthodontic separation: a randomized controlled trial

BackgroundThe low-level laser therapy (LLLT) and low-intensity pulsed ultrasound (LIPUS) have been recently applied to control pain during orthodontic treatment.ObjectiveTo evaluate and compare the effectiveness of LLLT and LIPUS in reducing pain induced by orthodontic separation.Study designA single-blinded randomized controlled trial.MethodsOne hundred and fifty patients were randomly assigned into three groups; LLLT group, LIPUS group, and control group. After 5 min from the separators’ placement, the first dose of the laser or the ultrasound was applied, the second dose was applied after 24 h, and the third dose was applied after 48 h on both maxillary and mandibular first molars. The exposure of laser was for 20 s at each point (maxillary and mandibular first molars), with an 810-nm aluminum-gallium-arsenide (AlGaAs) diode laser on continuous mode. The output power set at 150 mW, the energy density of 4 J/cm2, and a laser spot diameter of 7 mm were applied. Whereas the frequency of ultrasonic toothbrush was 1.6 MHz; and average output intensity was 0.2 W/cm2. The application was for 20 min (5 min on each first molar). The control group received the separators without another intervention. A Visual Analog Scale (VAS 100 mm) was used to assess pain intensity at several time intervals during the first four days after the separators’ placement.ResultsA total of 145 patients were assessed. There was a significant difference in pain perception among the three groups after 5 min (P = .002). The maximum pain level was reached after 24 h. However, the laser group and the ultrasound group showed a statistically significant decrease in pain scores compared to the control group at all the assessment time points (P < .001). Whereas there was no difference between the laser group and the ultrasound group in reducing the pain scores (P > .05).ConclusionsThe LLLT and the LIPUS effectively reduce the separation pain when applied in multiple doses without differences between them.Trial registrationThis trial was registered with the German Clinical Trials Register (DRKS). (https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID= DRKS00029991). Date of registration: 26/08/2022.

Effectiveness of Low Level Laser Therapy and Low Intensity Pulsed Ultrasound on Neuropathic Pain among the Experimentally Induced Peripheral Nerve Injury in Rat Model

Background: Peripheral nerve injury creates an impact on the inflammatory process, leading to an elevation inHypoxia-inducible factor-1 alpha levels, which contributes to the development and progression of neuropathicpain. An innovative approach to alleviating neuropathic pain involves targeting inflammation.Purpose: This study aims to compare the effect of Low-Level Laser Therapy (LLLT) and Low-Intensity PulsedUltrasound (LIPUS) on neuropathic pain among the experimentally induced peripheral nerve injury in rat model.Methods: Rats with induced sciatic nerve crush injury were randomly divided into three groups: control, LIPUStreatment, and LLLT treatment. Mechanical paw withdrawal threshold analysis was performed before the injuryand from POD 2nd, 7th, 14th, and 21st to assess effectiveness of the treatment.Result: Low-Level Laser Therapy (LLLT) group showing statistically greater improvement on POD 14 and 21compared to both the LIPUS group and the control group in terms of paw withdrawal threshold measurementsamong rats with crush-induced neuropathic pain (P &lt; 0.001).Conclusion: This study found that the use of LLLT has a beneficial effect in the management of neuropathic painand control of analgesia compared to LIPUS by inhibiting the upregulation of HIF-1α synthesis during ischemia,hypoxia, and inflammation. However further studies are recommended to analyze long term results in largersample to control neuropathic pain.

Effectiveness of Low-Level Laser Therapy and Low Intensity Pulsed Ultrasound in Sensory Recovery in Experimentally Induced Peripheral Nerve Injury Rat Model

Background: Peripheral nerve injuries are known to cause significant functional impairment and diminishedsensory recovery, necessitating the exploration of effective therapeutic interventions.Purpose: The purpose of this research is to find the effectiveness of low-level laser therapy (LLLT) and low intensitypulsed ultrasound (LIPUS) sensory recovery in an experimentally induced peripheral nerve injury rat model.Materials and Methods: In this study, 18 adult male wistar rats which are divided into LLLT (n = 6), LIPUS (n = 6),and control (n = 6) groups. All rats underwent a standardized procedure to induce peripheral nerve injury, whilethe control group received sham procedures. Hot-Plate test and Cold-Plate Tests were conducted for pre- andpost-operative evaluation of sensory recovery at POD 7, 14, 21 days.Results: The study’s findings revealed that LLLT exhibited significantly improved sensory recovery compared toLIPUS and control groups on POD 14 and 21, indicating its potential as a promising non-invasive intervention formanaging peripheral nerve injuries (P &lt;0.001).Conclusion: The study recommends that LLLT is more effective when compared with LIPUS in promoting sensoryrecovery and enhancing in a rat model of peripheral nerve injury. Positive outcomes indicate LLLT’s potential asa promising intervention for managing peripheral nerve injuries.

The Efficacy and Safety of Low‐Intensity Pulsed Ultrasound Therapy for the Treatment of Peyronie’s Disease (A Report of 106 Cases): A Retrospective Study

Objective: To evaluate the efficacy and safety of low‑intensity pulsed ultrasound (LIPUS) for the treatment of Peyronie’s disease (PD).Methods: To analyze the treatment effect of 106 PD patients, 56 patients treated with LIPUS as therapy group and 50 patients with oral L‐carnitine and vitamin E as control group. 56 patients were treated with LIPUS three times per week for four consecutive weeks (12 times totally). Penile erectile pain, erectile function, the size of penile plaques, and penile curvature were assessed for all of these 106 PD patients before treatment and at 4‐ and 24‐week follow‐ups to evaluate the treatment effect. Erectile pain was assessed by visual analog scale (VAS), while erectile function using the International Index of Erectile Function scale (IIEF‐5), and penile plaque size was measured by ultrasound. After alprostadil was injected into the penile body to induce a full erection, the penis was measured with a protractor at the maximum bending degree.Results: After 4‐weeks follow‐up, the VAS scores of the LIPUS group were significantly lower than the baseline (P &lt; 0.01), while no significant differences were found in the control group (P &gt; 0.05). After 24‐weeks follow‐up, the VAS scores of the control group reduced significantly but also were significantly higher than the LIPUS group (P &lt; 0.01). The IIEF‐5 scores of the LIPUS group were significantly higher than the baseline (P &lt; 0.01). While the IIEF‐5 scores of the control group showed no significant differences both after 4‐ and 24‐weeks follow‐up (P &gt; 0.05). The penile plaque size showed no significant differences after 4‐ and 24‐weeks follow‐up both in the LIPUS group and the control group (P &gt; 0.05). The penile curvature degrees showed a significant reduction after 4‐weeks follow‐up in LIPUS group (P &lt; 0.01). While the penile curvature degrees of the control group showed no significant differences both after 4‐ and 24‐weeks follow‐up (P &gt; 0.05). No complications, such as penile pain, hematoma, or skin ecchymosis, were observed during the entire process of LIPUS treatment, nor did they appear during follow‐up.Conclusions: In patients with acute PD, LIPUS could relieve erectile pain and improve erectile dysfunction. Moreover, it appears not to reduce plaque size and not to have a clinically significant effect on penile curvature. Furthermore, LIPUS also shows a good safety profile during the management of PD and should be recommended for the clinical management of PD.

Neuropsychiatric Behavioral Assessments in Mice After Acute and Long-Term Treatments of Low-Intensity Pulsed Ultrasound.

Introduction: To evaluate whether both acute and chronic low-intensity pulsed ultrasound (LIPUS) affect brain functions of healthy male and female mice. Methods: Ultrasound (frequency: 1.5MHz; pulse: 1.0kHz; spatial average temporal average (SATA) intensity: 25mW/cm2; and pulse duty cycle: 20%) was applied at mouse head in acute test for 20minutes, and in chronic experiment for consecutive 10days, respectively. Behaviors were then evaluated. Results: Both acute and chronic LIPUS at 25mW/cm2 exposure did not affect the abilities of movements, mating, social interaction, and anxiety-like behaviors in the male and female mice. However, physical restraint caused struggle-like behaviors and short-time memory deficits in chronic LIPUS groups in the male mice. Conclusion: LIPUS at 25mW/cm2 itself does not affect brain functions, while physical restraint for LIPUS therapy elicits struggle-like behaviors in the male mice. An unbound helmet targeted with ultrasound intensity at 25-50mW/cm2 is proposed for clinical brain disease therapy.

Macrophage-targeted ultrasound nanobubbles for highly efficient sonodynamic therapy of atherosclerotic plaques by modulating M1-to-M2 polarization

Background and aimsSonodynamic therapy (SDT) is a new approach for the treatment of atherosclerosis (AS), yet the poor targeting ability of sonosensitizers limits its therapeutic efficacy. Herein, we reported a plaque-targeted nanoplatform modified with macrophage type A scavenger receptor (SR-A)-targeted peptide (designated as SR-A-Ce6NB) to augment the efficacy of low-intensity pulsed ultrasound (LIPUS)-mediated SDT of atherosclerotic plaque. MethodsSR-A-Ce6NB was fabricated by thin hydration method and biotin-avidin system, and its physicochemical properties, biocompatibility and plaque-targeting ability were investigated. RAW 264.7 cells were used for in vitro experimental studies. Male 6-week-old apolipoprotein E-deficient mice were fed a high-fat diet for 16 weeks to induce aortic atherosclerotic plaques. Plaque-bearing mice were randomly allocated into five groups (n = 6): control group, Ce6 + LIPUS group, Ce6NB + LIPUS group, SR-A-Ce6NB + LIPUS group and atorvastatin group. After treatment in each group, the aortic artery was harvested for Oil red O, H&E, Masson's trichrome staining, immunohistochemical and immunofluorescent staining. ResultsSR-A-Ce6NB with high stability and excellent biocompatibility was successfully fabricated. SR-A-Ce6NB could actively target activated macrophages and selectively accumulate in the plaque. SR-A-Ce6NB could be triggered by LIPUS and had a more potent sonodynamic effect than free Ce6 to potentiate SDT. SR-A-Ce6NB-mediated SDT enhanced the anti-atherogenic effect via modulating M1-to-M2 macrophage polarization and had an earlier onset of action on plaque than the statin-mediated effect. No apparent side effect was observed after intravenous SR-A-Ce6NB injection and LIPUS exposure. ConclusionsMacrophage-targeted nanoplatform SR-A-Ce6NB-mediated SDT provides a safe, effective and preferable anti-atherogenic therapy by mediating M1-to-M2 macrophage polarization.

Low-intensity pulsed ultrasound phonophoresis with diclofenac alleviated inflammation and pain via downregulation of M1 macrophages in rats with carrageenan-induced knee joint arthritis

ObjectiveThis study aimed to investigate the effects of low-intensity pulsed ultrasound (LIPUS) phonophoresis with diclofenac on inflammation and pain in the acute phase of carrageenan-induced arthritis in rats. Design60 male Wistar rats were randomly divided into the arthritis, diclofenac, LIPUS, phonophoresis, and sham-arthritis control groups. LIPUS and transdermal diclofenac gel were applied to the lateral side of the inflamed knee for 7 days, initiated postinjection day 1. In the phonophoresis group, diclofenac gel was rubbed onto the skin, followed by LIPUS application over the medication. Knee joint transverse diameters, pressure pain thresholds (PPTs), and paw withdrawal thresholds (PWT) were evaluated. The number of CD68-, CD11c-, and CD206-positive cells, and IL-1β and COX-2 mRNA expression were analyzed 8 days after injection. ResultsIn the phonophoresis group, the transverse diameter, PPT, PWT significantly recovered at the day 8 compared to those in the LIPUS and diclofenac groups. The number of CD68- and CD11c-positive cells in the phonophoresis group was significantly lower than that in the LIPUS and diclofenac groups, but no significant differences were observed among three groups in CD206-positive cells. IL-1β and COX-2 mRNA levels were lower in the phonophoresis group than in the arthritis group, although there were no differences among the LIPUS, diclofenac, and phonophoresis groups. ConclusionLIPUS phonophoresis with diclofenac is more effective to ameliorate inflammation and pain compared to diclofenac or LIPUS alone, and the mechanism involves the decrease of M1 macrophages.