Search Results (364)

Musculoskeletal pain is a major cause of disability and long-term analgesic use, increasing interest in safe non-pharmacological interventions. This focused narrative review examines light-emitting diode (LED)-based photobiomodulation (PBM) for musculoskeletal pain, integrating molecular, mechanistic, clinical, and translational evidence. Red and near-infrared LED-PBM may act through mitochondrial and non-mitochondrial photoacceptors, modulation of ATP production, reactive oxygen species, nitric oxide, calcium signaling, inflammatory pathways, oxidative stress responses, and extracellular matrix repair. Clinical evidence suggests a potential benefit in selected conditions, particularly temporomandibular disorders, fibromyalgia, cervical and myofascial pain, tendon and plantar fascia disorders, knee osteoarthritis, and mild-to-moderate peripheral nerve compression, while findings for non-specific low back pain remain inconsistent. The reviewed literature indicates that therapeutic response depends less on emitter identity alone than on wavelength, irradiance, radiant exposure, treatment geometry, target depth, timing, disease phenotype, and protocol quality. LED-based PBM appears generally well tolerated and clinically promising as an adjunct to rehabilitation, but current evidence is limited by heterogeneous devices, incomplete dosimetry, variable comparators, and short follow-up. Future studies should prioritize standardized reporting, depth-aware dosing, phenotype-based recruitment, biomarker-linked outcomes, and direct laser–LED comparisons under dosimetrically matched conditions. Full article

Orthodontic pain, a fundamental biological response to mechanically induced tooth movement, is primarily associated with sterile inflammation and neurogenic processes within the periodontal ligament (PDL). Although photobiomodulation therapy (PBMT) has been widely investigated as a nonpharmacological approach for pain attenuation, its mechanisms of action remain incompletely understood, and current interpretations are often limited to peripheral anti-inflammatory effects. This review re-examines the biological basis of orthodontic pain by integrating evidence derived predominantly from in vitro and in vivo experimental studies. Particular emphasis is placed on neurogenic inflammation, neuropeptide regulation, and neuron–glia interactions along the trigeminal nociceptive pathway. PBMT can reduce periodontal inflammatory/neuropeptide-related markers and pain-related behaviors in selected models; however, evidence for direct central neuron–glia modulation remains largely marker-based and parameter-dependent. Direct functional validation of trigeminal circuit modulation (e.g., electrophysiological recordings or calcium imaging) remains limited in orthodontic pain models; thus, the proposed neuroimmune mechanisms should be interpreted as testable hypotheses for future work. By synthesizing mechanistic insights across multiple biological levels, this review proposes a broader framework for understanding PBMT-mediated pain modulation extending beyond conventional peripheral models. These perspectives may help clarify inconsistencies in the reported outcomes and provide a rationale for future hypothesis-driven experimental and translational research. Full article

Laser acupuncture, defined as photobiomodulation or low-level laser therapy applied to specific acupuncture points, has been proposed as a non-invasive adjunctive strategy in oral and dental care. This umbrella review aimed to synthesize and critically appraise systematic reviews evaluating laser acupuncture in dental and orofacial conditions. The review followed PRISMA 2020 recommendations and was prospectively registered in PROSPERO. PubMed, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to 12 May 2026. Systematic reviews with or without meta-analysis were included. Methodological quality was assessed using AMSTAR 2, and findings were narratively synthesized considering methodological quality, overlap, consistency, dosimetric heterogeneity, and clinical applicability. From 263 records identified, six systematic reviews published between 2021 and 2024 met the eligibility criteria. The included reviews addressed three main domains: temporomandibular disorders, dental-related neuropathies, and pediatric dental outcomes. Laser acupuncture protocols used red to near-infrared wavelengths, mainly between 690 and 980 nm, but varied substantially in fluence, energy delivery, irradiation time, session frequency, and acupoint selection. The most consistent signal was observed for short-term pain reduction in temporomandibular disorders, although comparative evidence did not support laser acupuncture as superior to established conservative therapies. Evidence for dental-related neuropathies was associated with possible improvements in neurosensory and motor outcomes, while pediatric evidence suggested possible short-term changes in gag reflex, procedural pain, and bruxism-related outcomes; however, both domains were supported by only one systematic review each and should be considered preliminary and hypothesis-generating. No serious adverse events were reported, but harm reporting was limited. Overall, this umbrella review should be interpreted as an evidence map rather than as a source of high-certainty clinical recommendations. Laser acupuncture may represent an emerging adjunctive approach for selected dental and orofacial indications; however, current evidence remains limited and heterogeneous and does not support standardized protocols, stand-alone use, or definitive clinical recommendations. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) and the accumulation of tau in the brain, which triggers robust innate immune responses. Growing evidence indicates that neuroinflammation contributes to AD progression by overactivating microglia through the release of cytokines and chemokines. In general, chemokines can disrupt neuronal communication and promote blood–brain barrier permeability. Peripheral immune cells are mobilized into the brain by a gradient of chemokines. These processes link peripheral immune responses with substantial T-cell infiltration into the CNS parenchyma, leptomeninges and cerebrospinal fluid of both AD mice and AD patients. This finding underscores the relevance of the adaptive immune system, particularly T and B cells, in AD neuropathology. T-cell infiltration into the brain can influence amyloid clearance through chemokine signalling. However, chemokines play a critical role in AD by either promoting or suppressing disease progression. The infiltration of peripheral T and B cells into the brain parenchyma can exacerbate neuronal loss, yet it may also exert neuroprotective effects. Despite the presence of CD4⁺ and CD8⁺ T cells in postmortem brains of AD patients, debate continues about their role in AD brains, in terms of whether they are protective or detrimental. Understanding the complex role of chemokines in controlling innate and adaptive immune responses by modulating neuron–glia interactions (involving astrocytes and microglia) may provide novel therapeutic approaches for AD. Targeting chemokine signalling or treating with drugs that can prevent the recruitment of immune cells may be promising strategies for treating AD neuropathology. Therapies that prevent the overactivation of T cells in the brain could lead to protective strategies against AD. In fact, regulatory T cells (Tregs) could delay the onset of cognitive symptoms, because they suppress inflammation and slow the accumulation of Aβ plaques and p-Tau in the brain. Complementary strategies, such as photobiomodulation, nanoparticle, and T-cell-based approaches, could mitigate AD progression in patients. Full article

Physical energy-based therapies are non-invasive adjunctive interventions that deliver mechanical, electromagnetic, light, or radiofrequency/thermal energy to tissues with the aim of reducing symptoms and improving tolerance of active rehabilitation. Osteoarthritis (OA) is a heterogeneous whole-joint disorder in which cartilage degeneration, subchondral bone remodeling, synovitis, peri-articular tissue dysfunction, neuromuscular impairment, and pain sensitization may interact to produce pain, stiffness, and activity restriction. As conservative therapy for OA, education, progressive therapeutic exercise, weight management when indicated, and self-management remain the core of care. Nevertheless, some patients cannot fully participate in exercise because of pain, fear of movement, load intolerance, comorbidity, or limited access to supervised rehabilitation. This narrative review synthesizes evidence published mainly between 2016 and 2026 for extracorporeal shock wave therapy (ESWT), photobiomodulation/low-level laser therapy (PBMT/LLLT), pulsed electromagnetic field therapy (PEMF), transfer energy capacitive and resistive/capacitive–resistive electric transfer (TECAR/CRET) therapy, body weight support and aquatic unloading strategies, and mechanosonic vibration therapies. The available literature suggests that ESWT and PBMT/LLLT may provide short- to mid-term pain and function benefits in selected patients with knee OA when parameters are aligned with evidence-supported dosing windows. PEMF and vibration therapies show promising but less consistent effects because protocols, devices, sham conditions, and populations vary. TECAR/CRET and unloading approaches are best interpreted as enabling tools that may reduce guarding, improve walking tolerance, or increase the quality of therapeutic exercise, rather than stand-alone disease-modifying treatments. Current national and society guidelines consistently prioritize exercise, education, and weight management; most of the modalities reviewed here are absent from guidelines or are supported only indirectly, which justifies cautious wording and individualized use. A practical application model is, therefore, time-limited and goal-oriented: identify the barrier to rehabilitation, select a modality with a plausible mechanism and published protocol, monitor pain and functional response, and discontinue the modality if it does not improve participation in active care. Full article

Background/Objectives: Gingivitis is one of the most prevalent inflammatory conditions in pediatric populations and represents a significant oral health burden worldwide. In addition to conventional approaches, emerging adjunctive therapies such as low-level laser therapy (LLLT), also known as photobiomodulation, have gained increasing attention. This review aims to evaluate current evidence regarding the clinical relevance and potential healthcare implications of LLLT in the management of gingival inflammation in children and adolescents. Methods: A structured narrative literature review was conducted, including experimental, animal, and clinical studies published between 2005 and 2025. Study selection and screening were performed independently by two reviewers. Methodological characteristics of the included pediatric clinical studies were qualitatively assessed, focusing on randomization, blinding, follow-up reporting, and adverse event monitoring. Results: Experimental studies demonstrate that LLLT enhances gingival cell proliferation and modulates inflammatory responses, while antimicrobial effects remain inconsistent. Animal studies indicate reductions in gingival inflammation and alveolar bone loss when LLLT is used adjunctively with conventional therapy. Clinical studies in pediatric populations report improvements in gingival indices and periodontal treatment needs, with no adverse effects observed. Conclusions: LLLT appears to be a safe, non-invasive adjunctive therapy with potential to improve oral health outcomes in pediatric populations. Its clinical applicability and high patient acceptability support its potential integration into broader oral healthcare strategies. However, further well-designed clinical trials with standardized protocols and long-term follow-up are required. Full article

The study evaluated bone repair in tibial defects of Wistar rats treated with 45S5 bioactive glass, either alone or combined with lyophilized heterologous fibrin biopolymer (HFB) and/or photobiomodulation therapy (PBM). Thirty-five animals were randomly assigned to five groups: control (CG), Bioactive glass (BG), Bioactive glass + HFB (BFG), Bioactive glass + PBM (BPG), and Bioactive glass + HFB + PBM (BFPG). After 42 days, the samples were analyzed by micro-computed tomography, histology (Hematoxylin–Eosin, Masson’s Trichrome, and Picrosirius Red), and histomorphometry. Histological and micro-CT findings demonstrated improved defect closure and better matrix organization in the BG and BFG groups. Histomorphometric analysis revealed significant differences among the groups (ANOVA, p < 0.0001), with the BG group showing the highest percentage of new bone formation (40.35 ± 4.14%), significantly higher than the BPG and BFPG groups. The addition of HFB did not impair bone repair and yielded intermediate results, whereas PBM did not demonstrate a positive effect on bone regeneration at the 42-day time point under the parameters used in this study. It can be concluded that bioactive glass, especially when used alone or in combination with heterologous fibrin biopolymer, promoted superior bone regeneration, while its association with photobiomodulation did not demonstrate additional benefit at 42 days. Full article

Purpose: To evaluate the anatomical and functional efficacy of photobiomodulation (PBM) therapy in patients with dry age-related macular degeneration (AMD) and to investigate structural predictors of visual response. Methods: This retrospective study included 47 eyes of 30 patients with dry AMD treated with PBM. Best-corrected visual acuity (BCVA) was recorded as Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, and visual change (ΔBCVA) was calculated. Spectral-domain optical coherence tomography parameters—central retinal thickness (CRT), central macular volume (ETDRS 9-subfield central zone), and photoreceptor layer integrity (external limiting membrane [ELM], ellipsoid zone [EZ], and interdigitation zone [IZ])—were assessed pre- and post-treatment. Age-Related Eye Disease Study (AREDS) stage was graded per eye. Because both eyes from some patients were included, generalized estimating equation (GEE) models with patient-level clustering were used to account for inter-eye correlation. Effect estimates were reported as unstandardized coefficients with 95% confidence intervals. Results: Visual acuity improved following PBM therapy, with mean ETDRS letter scores increasing from 75.0 ± 14.1 to 78.0 ± 12.1 letters. In the GEE model accounting for patient-level clustering, the estimated mean gain was 2.97 ETDRS letters (95% CI: 1.15 to 4.79; p = 0.001). Mean CRT showed no significant change following PBM therapy (210.32 ± 48.61 µm vs. 211.23 ± 50.27 µm; GEE estimate: +0.91 µm; 95% CI: −5.52 to 7.35; p = 0.780). Central macular volume likewise remained stable (0.1913 ± 0.030 vs. 0.1919 ± 0.033 mm³; GEE estimate: +0.0006 mm³; 95% CI: −0.0054 to 0.0067; p = 0.836). Photoreceptor layer integrity demonstrated limited structural change, with no significant time effect for EZ or IZ integrity in binary GEE models and no observed pre–post change in ELM integrity. In multivariable GEE analysis, baseline BCVA (p < 0.001), ELM integrity (p < 0.001) and central macular volume (p = 0.041) were associated with change in ETDRS letter score, whereas AREDS category, EZ integrity, and IZ integrity were not. Conclusions: PBM therapy demonstrated limited short-term anatomical change but variable functional outcomes in dry AMD. Baseline BCVA emerged as the primary determinant of visual response, suggesting that treatment benefit may be influenced predominantly by pre-treatment functional reserve. Full article

Photobiomodulation (PBM), the therapeutic application of red to near-infrared light, has demonstrated neuroprotective effects in preclinical CNS models, yet clinical translation remains inconsistent. This systematic review synthesises evidence for PBM across CNS applications to identify factors associated with therapeutic response. We searched five databases (MEDLINE, Embase, CENTRAL, Web of Science, Scopus) through January 2025 following PRISMA 2020 guidelines. Included studies employed PBM for CNS conditions with quantified neurological, cognitive, or functional outcomes; evidence quality was assessed using RoB 2, ROBINS-I, SYRCLE, and the GRADE framework. Thirty studies met inclusion criteria: 27 human studies (n ≈ 2244 participants) and 3 animal studies spanning Alzheimer’s disease, Parkinson’s disease, stroke, traumatic brain injury, and other CNS conditions. Dosimetry—particularly irradiance and light source type (laser vs. LED)—appears to be the primary factor associated with efficacy for Alzheimer’s disease (GRADE: Moderate); trans-cranial LED shows promise for Parkinson’s disease (GRADE: Low); trans-cranial 808 nm laser demonstrates no benefit for acute ischaemic stroke (GRADE: High). Systemic abscopal mechanisms may offer additional therapeutic pathways warranting investigation. These findings provide a condition-specific framework for rational PBM protocol development, supporting adequate irradiance via laser or intra-nasal delivery for Alzheimer’s disease, LED-based trans-cranial protocols for Parkinson’s disease, and integration of artificial intelligence for personalised optimisation. Full article

Background: Effective pain management is crucial during orthodontic treatments with fixed appliances, to ensure adequate patient compliance and to avoid treatment discontinuation. Photobiomodulation approaches, including Low Level Laser Therapy (LLLT) has received substantial attention, due to its potential as an effective, non-pharmacological analgesic modality, however, evidence pertaining to its efficacy is controversial. Our present study aims to evaluate the efficacy of LLLT vs. placebo, following placement of orthodontic elastic separators (ESs) in adult patients treated with fixed orthodontic appliances. Methods: A randomized, double-blind, split-mouth study was carried out, where n = 31 volunteers (18 male and 13 female; aged between 19 and 32 years) were enrolled. ESs were placed at the mesial and distal surfaces of the first permanent molars in both quadrants of lower, as well as upper jaws. Based on the assigned intervention, the four quadrants were divided as follows: three quadrants received LLLT treatment—using a 980 nm wavelength GaAlAs diode laser, with 0.1–0.2 W—according to three treatment regimes, i.e., regime 1 (R1): 6 J, continuous mode, R2: 12 J, continuous mode, and R3: 6 J, pulsed mode; while placebo treatment (P) was applied in the fourth quadrant. A questionnaire with a visual analogue scale (VAS; 0–100) was used for pain assessment (spontaneous pain and pain on mastication), scored directly after separation and after 6, 24, 48 and 72 h of both laser and placebo treatment application. Results: After the 24 h mark, significant differences were detected between the pain readings of LLLT-treated and placebo quadrants, both in resting position and during mastication (p < 0.05); pain readings were highest for R2, P, while lowest for R3 quadrants in resting position, and at R1 during mastication, respectively. Conclusions: Although findings of our study are exploratory in nature, they suggest that a single application of LLLT might be effective in reducing pain caused by ES placement, especially in the vulnerable 24 h following separation. Trial registration: clinicaltrials.gov ID NCT07456709 (date of registration: 2 March 2026, retrospectively registered). Full article

Background/Objectives: Photobiomodulation (PBM) is a biologically plausible adjunct for modulating orthodontic tissue response, but its role in conventional clear aligner therapy remains uncertain. This narrative review summarises the mechanistic rationale and clinical evidence on PBM used with clear aligners, focusing on treatment efficiency, predictability, patient-centred outcomes, and biological safety. Methods: Scopus was searched using PBM/low-level laser terms combined with orthodontics and clear aligners. Titles and abstracts were screened for human studies evaluating PBM as an adjunct to conventional staged clear aligner therapy and reporting treatment duration or alignment efficiency, tracking/predictability (for example, additional aligners, refinements, or fit-related outcomes), pain, or biological safety. Eight aligner-based clinical studies formed the core set. Results: The included studies comprised case reports, retrospective cohorts, pilot investigations, and one historical prospective nonrandomized comparison. Most evaluated short daily sessions of home-use near-infrared LED PBM, while some used external laser-based or combined adjunct protocols. Some studies reported shorter treatment duration, faster alignment, or fewer finishing aligners in PBM users, but these findings were difficult to attribute to PBM alone because altered tray-change intervals and close monitoring were common co-interventions. Aligner-specific pain outcomes were inconsistently reported. Limited safety data, based mainly on one retrospective pilot cohort assessing anterior teeth, found no statistically significant difference in root-volume change between PBM users and controls. Conclusions: PBM has been investigated as a potential adjunct in clear aligner orthodontics, but the available evidence remains preliminary, heterogeneous, and largely non-randomised. No high-quality randomized clinical evidence currently supports the clinical effectiveness or routine use of PBM in clear aligner orthodontics. At present, PBM should be regarded as an investigational adjunct rather than an established clinical recommendation, pending larger and better-designed trials with standardised device-specific protocols, objective adherence measures, movement-specific analyses, and longer follow-up for safety and patient benefit. Full article

Mesenchymal stem cells (MSCs) are central effectors in regenerative medicine, yet their clinical translation is hindered by inconsistent therapeutic outcomes and a lack of standardized light-delivery protocols. This review addresses an underexplored dimension of photobiomodulation (PBM): the divergent, wavelength-dependent signaling programs triggered in MSCs by red/near-infrared (NIR) versus blue light. By integrating biophysical principles of light delivery with a systems biology analysis of protein–protein interaction networks (STRING/GO), we delineate a “Dual Photonic Programming” framework. Red/NIR light (600–1100 nm) targets mitochondrial cytochrome c oxidase, activating a bioenergetic-anabolic program centered on PI3K/Akt/mTOR and Wnt/β-catenin—pathways essential for structural tissue repair. Blue light (400–500 nm) engages cytosolic flavins to drive a secretory-paracrine program that modulates vesicle trafficking and immunomodulatory cargo release. We further examine the dosimetric paradox, demonstrating how culture-environment optics and the Arndt–Schultz biphasic law govern the transition from regenerative stimulation to inhibitory oxidative stress. By tailoring photonic parameters to the MSC’s anatomical origin and metabolic baseline, PBM can serve as a high-fidelity bio-switch for orchestrated tissue repair, providing a mechanistic roadmap for standardized regenerative therapies. Full article

Background: This study aims to map the temporal evolution of light-based therapies and identify emerging technological trends in wearable photobiomodulation (PBM) devices. Materials and Methods: A bibliometric analysis (1970–2025) was conducted using three major databases: Scopus, PubMed, and Web of Science. The initial dataset, consisting of 117 articles, was processed using the Bibliometrix package in R (version 4.5.0), resulting in a final set of 110 articles. The analysis followed the TALL model (Tracking, Analysis, Layout, and Learning). Results: Scientific production on phototherapeutic devices began in the early 2000s, peaking in 2024, showing a productivity pattern typical of emerging or highly specialized fields. The period 2010–2023 represents a central thematic hub in research. During this time, new light sources (OLED and QLED) enabled the development of flexible, wearable, and implantable photonic devices. In the recent period (2024–2025), light-based therapies are increasingly integrated with network-connected biosensing systems for tissues or accessories, allowing adaptive treatments and remote monitoring. However, these next-generation devices are still undergoing consolidation and scientific maturation. Conclusions: The results highlight the rapid evolution of research on light-based therapies toward more integrated and clinically validated approaches, indicating growing scientific interest in personalized wearable PBM devices. Full article

Dry eye disease, a multifactorial and symptomatic disease characterized by tear film instability and ocular surface dysfunction, has emerged as an increasingly pressing global health concern—particularly against the backdrop of increasing digital device usage and the widespread application of virtual learning. Traditional pharmacotherapies, such as artificial tears, yield only transient symptomatic relief. Compared with pharmacological agents, surgical treatments are further restricted in clinical application, primarily because of their invasiveness, technical complexity, postoperative complications, and high costs. Consequently, the development of novel therapeutic strategies has emerged as imperative. This review summarizes advances in pharmacotherapy, including nanomedicine and biological agents, as well as emerging physiotherapies, such as photobiomodulation, thermal pulsation, and neurostimulation. These innovative therapeutic approaches address the partial limitations of conventional treatments through three main molecular mechanisms: improved drug delivery, multitargeted pharmacology, and enhanced biocompatibility. Nevertheless, the clinical translation of many innovative therapies requires large-scale clinical trials to validate clinical efficacy, optimize dosage regimens, and assess long-term safety profiles. In the future, integrating lifestyle modifications, effective clinician–patient communication, and patient-centric diagnostic approaches will facilitate the establishment of therapeutic alliances and support the success of precision medicine. Full article

Background/Objectives: Burning mouth syndrome (BMS) is a chronic idiopathic orofacial pain disorder characterized by persistent intraoral burning in the absence of detectable mucosal alterations. Diagnosis is challenging due to the lack of specific biomarkers and the need to exclude numerous systemic and local conditions that can mimic oral burning. This literature review aims to summarize current and emerging therapeutic strategies for BMS. Methods: A structured and filtered search of PubMed, Scopus, and Web of Science identified studies evaluating pharmacological, phytotherapeutic, and non-pharmacological interventions. Results: Various antidepressants, anticonvulsants, benzodiazepines, H2 receptor antagonists, and low-dose naltrexone have demonstrated varying degrees of symptom reduction, while alpha lipoic acid (ALA) and phytomedicines such as capsaicin, Hypericum perforatum, Catuama, lycopene, crocin, and melatonin show mixed clinical benefits. Non-pharmacological approaches, including photobiomodulation (PBM), oral cryotherapy, neuromodulation techniques, and cognitive behavioral therapy, also provide meaningful symptom improvement in many patients. Conclusions: Across all modalities, therapeutic responses remain heterogeneous and generally incomplete, underscoring the absence of a universally effective treatment. Current evidence supports an individualized and multidisciplinary approach that integrates pharmacological, psychological, and adjunctive therapies to address the multifactorial nature of BMS. Full article