Diabetes in spotlight: current knowledge and perspectives of photobiomodulation utilization.

Introduction: Diabetes is a global health concern characterized by chronic hyperglycemia resulting from insulinopenia and/or insulin resistance. The rising prevalence of diabetes and its associated complications (ulcers, periodontitis, healing of bone defect, neuropathy, retinopathy, cardiopathy and nephropathy) necessitate innovative therapeutic approaches. Photobiomodulation (PBM), involves exposing tissues and cells to low-energy light radiation, leading to biological effects, largely via mitochondrial activation. Methods: This review evaluates preclinical and clinical studies exploring the potential of PBM in diabetes and its complications, as well all clinical trials, both planned and completed, available on ClinicalTrials database. Results: This review highlights the variability in PBM parameters across studies, hindering consensus on optimal protocols. Standardization of treatment parameters and rigorous clinical trials are needed to unlock PBM's full therapeutic potential. 87 clinical trials were identified that investigated PBM in diabetes mellitus (with 5,837 patients planned to be treated with PBM). Clinical trials assessing PBM effects on diabetic neuropathy revealed pain reduction and potential quality of life improvement. Studies focusing on wound healing indicated encouraging results, with PBM enhancing angiogenesis, fibroblast proliferation, and collagen density. PBM's impact on diabetic retinopathy remains inconclusive however, requiring further investigation. In glycemic control, PBM exhibits positive effects on metabolic parameters, including glucose tolerance and insulin resistance. Conclusion: Clinical studies have reported PBM-induced reductions in fasting and postprandial glycemia without an increased hypoglycemic risk. This impact of PBM may be related to its effects on the beta cells and islets in the pancreas. Notwithstanding challenges, PBM emerges as a promising adjunctive therapy for managing diabetic neuropathy, wound healing, and glycemic control. Further investigation into its impact on diabetic retinopathy and muscle recovery is warranted.

Photobiomodulation inhibits neuronal firing in the superficial but not deep layer of a rat spinal dorsal horn.

Photobiomodulation (PBM) has attracted attention as a treatment for chronic pain. Previous studies have reported that PBM of the sciatic nerve inhibits neuronal firing in the superficial layers (lamina I-II) of the spinal dorsal horn of rats, which is evoked by mechanical stimulation that corresponds to noxious stimuli. However, the effects of PBM on the deep layers (lamina III-IV) of the spinal dorsal horn, which receive inputs from innocuous stimuli, remain poorly understood. In this study, we examined the effect of PBM of the sciatic nerve on firing in the deep layers of the spinal dorsal horn evoked by mechanical stimulation. Before and after PBM, mechanical stimulation was administered to the cutaneous receptive field using 0.6-26.0 g von Frey filaments (vFFs), and vFF-evoked firing in the deep layers of the spinal dorsal horn was recorded. The vFF-evoked firing frequencies were not altered after the PBM for any of the vFFs. The inhibition rate for 26.0 g vFF-evoked firing was approximately 13 % in the deep layers and 70 % in the superficial layers. This suggests that PBM selectively inhibits the transmission of pain information without affecting the sense of touch. PBM has the potential to alleviate pain while preserving the sense of touch.

Clinical and ex-vivo effect of LASERs on prevention of early-enamel caries: systematic review & meta-analyses.

To investigate the in vivo and in situ effect of different types of lasers in prevention of enamel demineralization in high caries risk cases (around orthodontic brackets, around restoration and in caries susceptible pits and fissures). PubMed was searched using the following keyword sequence; (Laser therapy OR laser irradiation OR laser application) AND (enamel caries prevention OR enamel demineralization OR enamel remineralization OR early enamel caries OR early-enamel caries OR enamel resistance OR enamel decalcification OR white spot lesions WSLs OR incipient lesion OR enamel decay OR enamel Dissolution OR enamel microhardness) AND (clinical trial OR Randomized clinical trial OR In situ study). The latest literature search was ended by "30 January 2023". PubMed was used as a primary data base for study selection. Scopus, EBSCO, and Google scholar are checked in our study after results of systematic search on PubMed. Only duplicates were found. Two meta-analyses were carried out. The first, clinical meta-analysis on incidence of white spot lesions (WSLs) following CO2 laser irradiation of enamel. The second meta-analysis on ex-vivo/in situ effect of CO2 laser on microhardness of enamel. In each meta-analysis three studies were included. Risk of bias was assessed. The search identified eight studies (four ex-vivo and four clinical trials). Regarding the clinical meta-analysis, the overall standardized mean difference was 0.21 [ 95% confidence interval (CI): 0.15-0.30, p < 0.00001]. This indicates that the incidence of new WSLs in patients who received low power CO2 laser treatment was highly significantly lower than placebo groups. The heterogeneity was considerable (I2 = 71%). In the second meta-analysis, the overall standardized mean difference was 49.55 [ 95% confidence interval (CI): 37.74, 61.37, p < 0.00001]. This indicates that microhardness of enamel receiving low power (0.4-5 W) CO2 laser irradiation is highly significantly lower than control untreated enamel. The heterogeneity was substantial (I2 = 48%). Within the limitations of this study, Low level laser therapy concept with CO2 laser seems to be effective in preventing enamel caries.Prospero registration number: CRD42023437379.

Comparison of High-intensity Laser Therapy with Extracorporeal Shock Wave Therapy in the Treatment of Patients with Plantar Fasciitis: A Double-blind Randomized Clinical Trial.

Background: The most common cause of heel pain is plantar fasciitis (PF). Although conservative treatments relieve pain in more than 90% of patients, it may remain painful in some cases. This study aimed to compare High-intensity Laser Therapy (HILT) with Extracorporeal Shock Wave Therapy (ESWT) in patients with PF. Methods: In this double-blinded randomized clinical trial (conducted in Yazd, Iran, from May 2020 to March 2021), patients were classified into two groups, including the ESWT and HILT, using online randomization. Nine sessions, three times a week for 3 weeks, were the treatment period in both groups. Visual Analogue Score (VAS), Heel Tenderness Index (HTI), and the SF36 questionnaire were compared and analyzed statistically at the beginning and 9 months after treatment. Results: 38 patients (19 in each group) completed the study. Results showed that pain and patient satisfaction improved significantly 3 months after treatment. The VAS and HTI decreased 3 months after treatment in both groups, which was statistically significant (P<0.001). The SF36 score in both groups increased 3 months after treatment, and this increase was statistically significant (P<0.001). Although the two modalities were effective based on VAS, HTI, and SF36, a significant statistical difference was observed between them (P=0.03, P=0.006, P=0.002, respectively), and the HILT was more effective. Conclusion: ESWT and HILT decrease pain and increase patient satisfaction in PF. Besides, both methods are non-invasive and safe. However, there is a significant difference between them, and HILT is more effective. Trial registration number: IRCT20210913052465N1.

Devices used for photobiomodulation of the brain-a comprehensive and systematic review.

A systematic review was conducted to determine the trends in devices and parameters used for brain photobiomodulation (PBM). The revised studies included clinical and cadaveric approaches, in which light stimuli were applied to the head and/or neck. PubMed, Scopus, Web of Science and Google Scholar databases were used for the systematic search. A total of 2133 records were screened, from which 97 were included in this review. The parameters that were extracted and analysed in each article were the device design, actuation area, actuation site, wavelength, mode of operation, power density, energy density, power output, energy per session and treatment time. To organize device information, 11 categories of devices were defined, according to their characteristics. The most used category of devices was laser handpieces, which relate to 21% of all devices, while 28% of the devices were not described. Studies for cognitive function and physiological characterisation are the most well defined ones and with more tangible results. There is a lack of consistency when reporting PBM studies, with several articles under defining the stimulation protocol, and a wide variety of parameters used for the same health conditions (e.g., Alzheimer's or Parkinson's disease) resulting in positive outcomes. Standardization for the report of these studies is warranted, as well as sham-controlled comparative studies to determine which parameters have the greatest effect on PBM treatments for different neurological conditions.

Photobiomodulation therapy in improvement of harmful neural plasticity in sodium salicylate-induced tinnitus.

Tinnitus is a common annoying symptom without effective and accepted treatment. In this controlled experimental study, photobiomodulation therapy (PBMT), which uses light to modulate and repair target tissue, was used to treat sodium salicylate (SS)-induced tinnitus in a rat animal model. Here, PBMT was performed simultaneously on the peripheral and central regions involved in tinnitus. The results were evaluated using objective tests including gap pre-pulse inhibition of acoustic startle (GPIAS), auditory brainstem response (ABR) and immunohistochemistry (IHC). Harmful neural plasticity induced by tinnitus was detected by doublecortin (DCX) protein expression, a known marker of neural plasticity. PBMT parameters were 808 nm wavelength, 165 mW/cm2 power density, and 99 J/cm2 energy density. In the tinnitus group, the mean gap in noise (GIN) value of GPIAS test was significantly decreased indicated the occurrence of an additional perceived sound like tinnitus and also the mean ABR threshold and brainstem transmission time (BTT) were significantly increased. In addition, a significant increase in DCX expression in the dorsal cochlear nucleus (DCN), dentate gyrus (DG) and the parafloccular lobe (PFL) of cerebellum was observed in the tinnitus group. In PBMT group, a significant increase in the GIN value, a significant decrease in the ABR threshold and BTT, and also significant reduction of DCX expression in the DG were observed. Based on our findings, PBMT has the potential to be used in the management of SS-induced tinnitus.

Subthreshold micropulse laser therapy for early postoperative macular thickening following surgical removal of epiretinal membrane.

BACKGROUND: This study aimed to investigate the functional and anatomical outcomes of subthreshold micropulse laser (SMPL) therapy in eyes with early postoperative macular thickening after idiopathic epiretinal membrane (iERM) removal. METHODS: This was a prospective and interventional study. Forty-eight eyes from 48 patients with macular edema at 1 month after iERM removal were randomly divided into two groups. Patients in the SMPL group (n = 24) received SMPL therapy while no special intervention was used for the observation group (n = 24). Baseline demographic data and clinical findings before and at 1 and 3 months after SMPL treatment or observation, including best-corrected visual acuity (BCVA) and the changes in central subfield thickness (CST) and average macular thickness (AMT), were analyzed. RESULTS: An improvement in BCVA with a decrease in CST and AMT from baseline to the 3-month follow-ups were observed in both SMPL and observation groups. No significant difference in BCVA was observed between the SMPL group and observation group either in the 1-month (0.26 [0.15, 0.52] vs. 0.26 [0.15, 0.39], P = 0.852) or the 3-month (0.15 [0.10, 0.30] vs. 0.23 [0.15, 0.30], P = 0.329) follow-up. There was a greater reduction in CST in the SMPL group versus observation group between baseline and the 3-month follow-up (-77.8 ± 72.3 µm vs. -45.0 ± 46.9 µm, P = 0.049). The alteration in AMT did not differ between the two groups in either 1-month (-16.5 ± 20.1 µm vs. -19.7 ± 16.3 µm, P = 0.547) or 3-month (-36.9 ± 26.9 µm vs. -34.0 ± 20.1 µm, P = 0.678) follow-up. CONCLUSIONS: SMPL therapy led to a significant decrease in CST at the 3-month follow-up while did not significantly improve the visual acuity in patients with postoperative macular thickening following iERM surgery. TRIAL REGISTRATION: The study was registered on Aug 27, 2020 (Trial Registration Number: ChiCTR 2000037227).

Photobiomodulation effects on synovial morphology, iNOS gene, and protein expression in a model of acute inflammation.

PURPOSE: To evaluate morphological aspects and inducible nitric oxide synthase (iNOS) gene and protein expression in a model of acute inflammation. METHODS: Thirty-six female Wistar rats were assigned into three groups: control (saline, n = 12), sham (arthritis, n = 12), and PBM (arthritis and photobiomodulation, n = 12). Arthritis induction was performed with 200 µg of intra-articular Zymosan in sham and PBM animals. PBM was performed 24 h after induction with a laser device (λ = 808 nm, 25 mW of nominal power, fluence of 20 J/cm2, beam area of 0.02 mm2, time of 33 s, total energy of 0.825 J) with punctual and single dose application. Morphological analysis of joint structure (HE) and immunohistochemistry (anti-iNOS antibody) were performed on knee samples, and synovial tissue was submitted to RNA extraction, cDNA synthesis and gene expression analysis by quantitative polymerase chain reaction. Statistical analyses were performed with p < 0.05. RESULTS: It was observed an increase in the thickness of the synovial lining epithelium and inflammatory infiltrate in sham compared to PBM. Gene expression analysis showed higher iNOS expression in PBM, and iNOS protein expression decreased in PBM compared to sham. CONCLUSIONS: Photobiomodulation decreased inflammation in PBM animals, upregulated iNOS gene expression, however down egulated protein expression compared to sham.

Laser Therapy Effects on Periodontal Status: A Randomized Study Using Gaussian Network Analysis and Structural Equation Modeling Approach.

Background and Objectives: This paper aims to assess the role of laser therapy in periodontitis through an innovative approach involving computational prediction and advanced modeling performed through network analysis (Gaussian graphical models-GGMs) and structural equations (SEM). Materials and Methods: Forty patients, exhibiting periodontal pockets with a minimum depth of 5 mm, were randomly divided into two groups: a control group and a laser group. Four specific indicators were measured for each tooth, namely periodontal pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI), and the mean of six measured values was recorded at five time markers (baseline, 6 months, 1 year, 2 years, and 4 years). The assessment algorithm included enrollment, measurements, and differential non-surgical periodontal treatment, according to the group allocation. Scaling, root planing, and chlorhexidine 1% were conducted for the control group, and scaling, root planing and erbium, chromium:yttrium-scandium-gallium-garnet (Er,CR:YSGG) laser therapy were conducted for the laser group. Results: The main results highlight that the addition of laser treatment to scaling and root planing led to notable clinical improvements, decreasing the PPD values, reducing the BOP scores, and increasing the CAL. Conclusions: Notable relationships between the specific indicators considered were highlighted by both the GGMs and by SEM, thus confirming their suitability as proxies for the success of periodontal treatment.

Photobiomodulation combination therapy as a new insight in neurological disorders: a comprehensive systematic review.

Preclinical and clinical studies have indicated that combining photobiomodulation (PBM) therapy with other therapeutic approaches may influence the treatment process in a variety of disorders. The purpose of this systematic review was to determine whether PBM-combined therapy provides additional benefits over monotherapies in neurologic and neuropsychiatric disorders. In addition, the review describes the most commonly used methods and PBM parameters in these conjunctional approaches.To accomplish this, a systematic search was conducted in Google Scholar, PubMed, and Scopus databases through January 2024. 95 potentially eligible articles on PBM-combined treatment strategies for neurological and neuropsychological disorders were identified, including 29 preclinical studies and 66 clinical trials.According to the findings, seven major categories of studies were identified based on disease type: neuropsychiatric diseases, neurodegenerative diseases, ischemia, nerve injury, pain, paresis, and neuropathy. These studies looked at the effects of laser therapy in combination with other therapies like pharmacotherapies, physical therapies, exercises, stem cells, and experimental materials on neurological disorders in both animal models and humans. The findings suggested that most combination therapies could produce synergistic effects, leading to better outcomes for treating neurologic and psychiatric disorders and relieving symptoms.These findings indicate that the combination of PBM may be a useful adjunct to conventional and experimental treatments for a variety of neurological and psychological disorders.

Preventive versus curative photobiomodulation for oral mucositis in patients with multiple myeloma undergoing hematopoietic stem cell transplantation: which approach is more effective?

PURPOSE: There is increasing evidence that photobiomodulation (PBM) therapy is both an effective and safe approach in hematopoietic stem cell transplantation (HSCT) for both prevention and management of oral mucositis (OM), but its use in clinical practice is still limited and the timing of application is under discussion. The aim of this retrospective study was to evaluate possible differences between patients treated either with preventive or curative PBM therapy. METHODS: The retrospective case series included 24 patients suffering from multiple myeloma who underwent the same conditioning and transplantation protocol. Patients were treated either with preventive PBM starting from the first day of conditioning up to two days post-HSCT or with curative PBM (starting at OM onset for four consecutive days). OM score, pain, and functional parameters were recorded. RESULTS: All patients developed OM. Preventive PBM was significantly more effective in reducing OM severity (p < 0.0001) and pain (p < 0.0001) post-HSCT than curative PBM. Furthermore, we found a lower number of patients reporting discomfort in all subjective parameters (pain during swallowing, chewing, and speaking) in the preventive PBM group. No adverse events related to PBM therapy were recorded in both groups. CONCLUSION: The timing for PBM therapy in patients undergoing HSCT is crucial: when started on the first day of conditioning, it significantly reduces both pain and OM severity, providing an important benefit also in subjective oral functions such as speaking, swallowing, and chewing, thus increasing the overall adherence to the oncological therapies.

Photobiomodulation preconditioned diabetic adipose derived stem cells with additional photobiomodulation: an additive approach for enhanced wound healing in diabetic rats with a delayed healing wound.

In this preclinical investigation, we examined the effects of combining preconditioned diabetic adipose-derived mesenchymal stem cells (AD-MSCs) and photobiomodulation (PBM) on a model of infected ischemic delayed healing wound (injury), (IIDHWM) in rats with type I diabetes (TIDM). During the stages of wound healing, we examined multiple elements such as stereology, macrophage polarization, and the mRNA expression levels of stromal cell-derived factor (SDF)-1α, vascular endothelial growth factor (VEGF), hypoxia-induced factor 1α (HIF-1α), and basic fibroblast growth factor (bFGF) to evaluate proliferation and inflammation. The rats were grouped into: (1) control group; (2) diabetic-stem cells were transversed into the injury site; (3) diabetic-stem cells were transversed into the injury site then the injury site exposed to PBM; (4) diabetic stem cells were preconditioned with PBM and implanted into the wound; (5) diabetic stem cells were preconditioned with PBM and transferred into the injury site, then the injury site exposed additional PBM. While on both days 4, and 8, there were advanced histological consequences in groups 2-5 than in group 1, we found better results in groups 3-5 than in group 2 (p < 0.05). M1 macrophages in groups 2-5 were lower than in group 1, while groups 3-5 were reduced than in group 2 (p < 0.01). M2 macrophages in groups 2-5 were greater than in group 1, and groups 3-5 were greater than in group 2. (p ≤ 0.001). Groups 2-5 revealed greater expression levels of bFGF, VEGF, SDF- 1α, and HIF- 1α genes than in group 1 (p < 0.001). Overall group 5 had the best results for histology (p < 0.05), and macrophage polarization (p < 0.001). AD-MSC, PBM, and AD-MSC + PBM treatments all enhanced the proliferative stage of injury repairing in the IIDHWM in TIDM rats. While AD-MSC + PBM was well than the single use of AD-MSC or PBM, the best results were achieved with PBM preconditioned AD-MSC, plus additional PBM of the injury.

Traumatic Brain Injury Recovery with Photobiomodulation: Cellular Mechanisms, Clinical Evidence, and Future Potential.

Traumatic Brain Injury (TBI) remains a significant global health challenge, lacking effective pharmacological treatments. This shortcoming is attributed to TBI's heterogeneous and complex pathophysiology, which includes axonal damage, mitochondrial dysfunction, oxidative stress, and persistent neuroinflammation. The objective of this study is to analyze transcranial photobiomodulation (PBM), which employs specific red to near-infrared light wavelengths to modulate brain functions, as a promising therapy to address TBI's complex pathophysiology in a single intervention. This study reviews the feasibility of this therapy, firstly by synthesizing PBM's cellular mechanisms with each identified TBI's pathophysiological aspect. The outcomes in human clinical studies are then reviewed. The findings support PBM's potential for treating TBI, notwithstanding variations in parameters such as wavelength, power density, dose, light source positioning, and pulse frequencies. Emerging data indicate that each of these parameters plays a role in the outcomes. Additionally, new research into PBM's effects on the electrical properties and polymerization dynamics of neuronal microstructures, like microtubules and tubulins, provides insights for future parameter optimization. In summary, transcranial PBM represents a multifaceted therapeutic intervention for TBI with vast potential which may be fulfilled by optimizing the parameters. Future research should investigate optimizing these parameters, which is possible by incorporating artificial intelligence.

Efficacy of transcranial photobiomodulation in the treatment for major depressive disorder: A TMS-EEG and pilot study.

BACKGROUND: Major depressive disorder (MDD) was a prevalent mental condition that may be accompanied by decreased excitability of left frontal pole (FP) and abnormal brain connections. An 820 nm tPBM can induce an increase in stimulated cortical excitability. The purpose of our study was to establish how clinical symptoms and time-varying brain network connectivity of MDD were affected by transcranial photobiomodulation (tPBM). METHODS: A total of 11 patients with MDD received 820 nm tPBM targeting the left FP for 14 consecutive days. The severity of symptoms was evaluated by neuropsychological assessments at baseline, after treatment, 4-week and 8-week follow-up; 8-min transcranial magnetic stimulation combined electroencephalography (TMS-EEG) was performed for five healthy controls and five patients with MDD before and after treatment, and time-varying EEG network was analyzed using the adaptive-directed transfer function. RESULTS: All of scales scores in the 11 patients decreased significantly after 14-day tPBM (p < .01) and remained at 8-week follow-up. The time-varying brain network analysis suggested that the brain regions with enhanced connection information outflow in MDD became gradually more similar to healthy controls after treatment. CONCLUSIONS: This study showed that tPBM of the left FP could improve symptoms of patients with MDD and normalize the abnormal network connections.

Adjunctive Effect of Photobiomodulation Therapy with Nd:YAG Laser in the Treatment of Inferior Alveolar Nerve Paresthesia.

Background: Disruption of peripheral branches of the trigeminal nerve in the field of maxillofacial surgery is a known risk due to the close connection of these branches with the bony structures of the maxilla and mandible. As a result, injuries of the lingual nerve and inferior alveolar nerve take place within routine maxillofacial surgery procedures, including local anesthetic injection, wisdom tooth surgery, and dental implant placement, resulting in paresthesia and dysesthesia. During the last three decades, low-level lasers (LLL) have been frequently used in various medical fields. Lately, this application has increased in several sectors. Methods and materials: This experiment was designed to explore the effect of low-level laser therapy (LLLT) with Nd:YAG on the paresthesia and dysesthesia of the lower lip. This ethics committee of Tbzmed, Tabriz, Iran, proved the present experiment with ethical code: IR.TBZMED.REC.1401.839. Results: After completing 10 sessions of laser therapy for the case group consisting of 25 patients with lower lip anesthesia, the visual analog scale index results revealed that following six sessions of laser therapy, a significant difference appeared in contrast to the control group. Also, according to the two-point tests, significant difference among the experimental and the control group appeared after ninth session of the laser therapy. Conclusions: Altogether, these data suggested LLLT with Nd:YAG as an effective treatment option for decreasing the anesthesia of the lower lip.

Effect of low-level laser therapy in wound healing of primary molar teeth extraction.

INTRODUCTION: Tooth extraction in children requires attention to wound healing and pain management, which are influenced by patient-related factors and behavioral guidance. AIM OF THE STUDY: The study aimed to evaluate the effect of LLLT on healing sockets in pediatric patients with bilateral primary molar teeth extraction and determine its impact on pain management. METHODS: 6-10 years of age, systemically healthy, and with atraumatic extraction indications of bilateral primary molar teeth were included in the study (n = 40). In the first session, randomly selected teeth were extracted under local anesthesia. In the control group, only clot formation in the socket was observed and photographed. The other group extractions were performed 2 weeks later. The low-level laser therapy (LLLT) group was treated with a 980 nm wavelength, in a continuous emission mode, 0.5 W power, 300 J of energy, 400 µm tip, 60 s diode laser and photographed. Nonepithelialized surface measurements were performed using ImageJ. Pain assessment was performed using the Wong-Baker Pain Scale. Statistical analyses were performed using SPSS software. RESULTS: There was a statistically significant difference between the groups in the Wong-Baker values in 3rd day (p < 0.05). In soft tissue healing on the 3rd and 7th day, the nonepithelialized surface of the laser socket was smaller than that of the control group, and the measurement results were found to be statistically significant (p < 0.05). CONCLUSION: Although LLLT was not found to be very effective in reducing postoperative discomfort after extraction of primary molars, it provided better wound healing in extraction sockets.

Clinical and thermographic evaluation after lower third molar extractions and the application of different photobiomodulation protocols: double-blind randomised clinical trial.

OBJECTIVES: to compare the parameters of pain, oedema, temperature, and soft tissue closure in dental sockets that received two different photobiomodulation (PBM) protocols following extractions. MATERIALS AND METHODS: Thirty-one participants had their teeth 38 and 48 extracted. Subsequently, one of the dental sockets received PBM at a wavelength (WL) of 808 nanometers (808 group- nm) and the other dental socket received the PBM at WLs of 808 nm and 660 nm, simultaneously (808 + 660 group). The PBM was applied immediately after the surgical procedure and on the 3rd and 7th days. RESULTS: The mean of Visual Analogue Scale (VAS) values for pain were 1.45 for the 3rd day and 0.52 for the 7th day in the 808 + 660 and 808 group, respectively. The mean the pogonion-tragus measurement, used to assess facial oedema on the 3rd day, was 15.38 cm (range 13.5-17.5) in the 808 + 660 group and 15.48 cm (range 14.0-17.5) in the 808 group. The mean facial temperatures in the 808 + 660 group were 34.9 degrees Celsius (ºC) (range 33.5-36.4) on the 3rd day and 35 ºC (range 33.4-36.4) on the 7th day. In the 808 group, the mean temperatures were 34.9 ºC (range 33.9-36.2) on the 3rd day and 34.9 ºC (33.7-36.2) on the 7th day. Regarding the dimensions of the dental socket, the mean were similar for both groups. Significant differences between the groups were only observed in the pain parameter and only on the 7th day, being greater for the 808 + 660 group (p = 0.031). CONCLUSIONS: The association of the 660 nm with 808 nm, and the increase in energy did not showed more benefits in pain reduction oedema, or acceleration of the closure of the soft tissues of the dental sockets of lower third molars, in the protocols used here. CLINICAL RELEVANCE: There is no need to combine lasers at wavelengths of 660 and 808 nm to reduce oedema, pain and repair of soft tissues after extraction of lower third molars. CLINICAL TRIAL REGISTRATION: This trial was registered in the Brazilian Registry of Clinical Trials (ReBEC) with the following code: RBR-66pyrh8, on 29th December, 2022.

Effect of photobiomodulation therapy on pain perception during anesthetic puncture of dental local anesthesia: A systematic review.

BACKGROUND: Local anesthetic puncture is often related to the experience of pain. This study aimed to systematically analyze the literature on changes in pain perception during the anesthetic puncture of dental local anesthesia after Photobiomodulation Therapy (PBMT). MATERIAL AND METHODS: An electronic search was performed in eight primary databases (Embase, LILACS, BBO, LIVIVO, MedLine via PubMed, SciELO, Scopus, and Web of Science) and three additional ones (EASY, Google Scholar, and OATD) to partially capture the "gray literature". The PICO strategy was used to identify randomized clinical trials evaluating the analgesic effect of PBMT in the anesthetic puncture site of dental local anesthesia compared to placebo or control groups, without restrictions on publication language and year. Two reviewers extracted the data and assessed the individual risk of bias of the eligible studies using the Cochrane Collaboration Risk of Bias Tool version 2.0. RESULTS: The electronic search found 3,485 records, of which eight met the eligibility criteria and were included in the qualitative synthesis. The studies were published from 2011 to 2022. None of the included studies had a low risk of bias. PBMT groups showed no significant difference in pain scores compared to placebo and control groups of most studies. CONCLUSION: Based on a low to very low certainty of evidence, PBMT seems to have no effect on pain perception during anesthetic puncture in patients undergoing dental local anesthesia.

The effect of combined red, blue, and near-infrared light-emitting diode (LED) photobiomodulation therapy on speed of wound healing after superficial ablative fractional resurfacing.

Objective of the study is to assess the effects of wound healing with a commercially available light emitting diode (LED) photo biomodulation (PBM) device that emits three wavelengths (465, 640 and 880nm) after ablative fractional laser (AFL) treatment to healthy skin on the bilateral inner biceps. We conducted a prospective intraindividual randomized controlled study with 25 volunteers. AFL treatment was performed on healthy skin of the bilateral inner biceps. Subjects applied the LED light device for 30 min to the assigned bicep 3 times a week over 4 weeks, beginning on day 0. Subjects were followed up on days 2, 4, 6, 9, 13, 20 and 27 for treatment with the PBM device, clinical digital photography of the test and control sites, and in-person subject assessment, with follow ups on days 34 and 55 for clinical photography and assessment. Three blinded evaluators were asked to determine which bicep healed faster between day 0 to day 13. Pain, discomfort, and itch were also assessed. The three blinded evaluators chose the treatment arm as the faster healed arm in greater than 50% of the images, although the results were not statistically significant. There was no statistically significant difference between test and control arms in terms of pain, discomfort and itch. In conclusion, PBM therapy has the potential to improve wound healing. In this study, a three wavelength PBM device resulted in some subjects achieving faster healing after AFL but the results were not statistically significant.

Translation from Preclinical Research to Clinical Trials: Brain-Gut Photobiomodulation Therapy for Alzheimer's Disease.

Recently, novel non-pharmacological interventions, such as photobiomodulation (PBM) therapy, have shown promise for the treatment of Alzheimer's disease (AD). This article outlines the translation from the preclinical to clinical stages of an innovative brain-gut PBM therapy in a mouse model of AD, a pilot clinical trial involving mild-to-moderate AD patients, and a continuing pivotal clinical trial with a similar patient population. In a mouse model of AD (Aß25-35), daily application of brain-gut PBM therapy to both the head and the abdomen produced a neuroprotective effect against the neurotoxic effects of an Aß25-35 peptide injection by normalizing all the modified behavioral and biochemical parameters. The pilot clinical trial to evaluate brain-gut PBM therapy demonstrated the tolerability and feasibility of the novel PBM-based treatment for mild-to-moderate AD patients. Compared to the sham patients, the PBM-treated patients had lower Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) comprehension sub-scores, higher forward verbal spans, and lower Trail Making Test (TMT) Part B (TMT-B) execution times, which suggest an improvement in cognitive functions. This pilot study provided important information for the design of a novel pivotal clinical trial, currently in progress, to assess the efficacy of brain-gut PBM therapy in a larger sample of AD patients. This pivotal clinical trial could demonstrate that brain-gut PBM therapy is a safe, well-tolerated, and efficient disease-modifying treatment for mild-to-moderate AD patients and that it has medical and economic benefits.