Protocol for a Single-Arm Feasibility Study of Photobiomodulation for Fatigue, Depression, and Pain in Inflammatory Bowel Disease.

BACKGROUND: There are limited treatment options for mental health comorbidities associated with Inflammatory Bowel Disease (IBD), although they have been shown to negatively affect the course of IBD and multiple important areas of functioning. Photobiomodulation (PBM) is a new therapeutic intervention using laser-generated low-powered light therapy that has shown early promise in alleviating fatigue, depression, and pain in chronic illness. METHODS: This prospective, single-arm pilot study aims to assess the feasibility and efficacy of PBM in the treatment of fatigue, depression, and pain in youth with IBD. We will recruit 28 young adults with IBD who will receive PBM in addition to treatment as usual. The primary outcome will be fatigue, while secondary outcomes will include depression, pain, quality of life, inflammatory markers, alterations in microbiome composition, physical activity, and functioning. Outcome measures will be assessed at baseline, after a 10-week control period (pre-PBM), at 20 weeks (post-PBM), and at 30 weeks. Feasibility will be assessed by attendance, recruitment rates, and participants' views of PBM. Mixed-effects linear regression modelling will be used to assess the PBM effect on continuous outcomes (fatigue, depression, anxiety and stress scores, and inflammation levels). RESULTS: The study will provide preliminary indicators of PBM feasibility and efficacy in IBD.

Remote Photobiomodulation Treatment for the Clinical Signs of Parkinson's Disease: A Case Series Conducted During COVID-19.

Objective: To assess whether remote application of photobiomodulation (PBM) is effective in reducing clinical signs of Parkinson's disease (PD). Background: PD is a progressive neurodegenerative disease for which there is no cure and few treatment options. There is a strong link between the microbiome-gut-brain axis and PD. PBM in animal models can reduce the signs of PD and protect the neurons from damage when applied directly to the head or to remote parts of the body. In a clinical study, PBM has been shown to improve clinical signs of PD for up to 1 year. Methods: Seven participants were treated with PBM to the abdomen and neck three times per week for 12 weeks. Participants were assessed for mobility, balance, cognition, fine motor skill, and sense of smell on enrolment, after 12 weeks of treatment in a clinic and after 33 weeks of home treatment. Results: A number of clinical signs of PD were shown to be improved by remote PBM treatment, including mobility, cognition, dynamic balance, spiral test, and sense of smell. Improvements were individual to the participant. Some improvements were lost for certain participants during at-home treatment, which coincided with a number of enforced coronavirus disease 2019 (COVID-19) pandemic lockdown periods. Conclusions: Remote application of PBM was shown to be an effective treatment for a number of clinical signs of PD, with some being maintained for 45 weeks, despite lockdown restrictions. Improvements in clinical signs were similar to those seen with the application of remote plus transcranial PBM treatment in a previous study. Clinical Trial Registration number: U1111-1205-2035.

Modifying the Microbiome as a Potential Mechanism of Photobiomodulation: A Case Report.

Objective: The objective of this case study was to elucidate the effect of photobiomodulation (PBM) on the microbiome. Background: The gut microbiome has been identified as a key component of health, with gut dysbiosis, characterized by decreased microbial diversity and an altered microbial composition, being recognized as instrumental in many diseases and disorders. Previous research has suggested that the gut microbiome can be favorably altered in animal models using PBM. Materials and methods: The participant had their microbiome tested on nine occasions, three times before any treatment, three times after radiotherapy and commencement of immunotherapy for breast cancer, and three times after PBM treatment. The PBM treatment consisted of infrared laser treatment (904 nm; 700 Hz pulse frequency, 861.3 total joules) to the abdomen three times per week for 11 weeks. Results: The microbiome of the participant showed significant changes in diversity after PBM treatment, but not after cancer therapy, with an increase in the number of known beneficial bacteria (Akkermansia, Faecalibacterium, and Roseburia) and decrease in the number of potentially pathogenic genera. Conclusions: The results suggested the possibility that PBM may alter the microbiome and thus it represents a therapeutic avenue for chronic diseases with otherwise limited treatment options.

Effect of Transcutaneous Radial Artery Photobiomodulation on Continuous Measures of Interstitial Glucose in a Single Subject: A Brief Report.

Background: Intravenous blood irradiation with light is purported to reduce blood sugar levels in people with diabetes mellitus (DM). Transcutaneous light emitting devices are marketed for use in modulating glucose levels, yet evidence of effectiveness is scarce. Materials and methods: In a single subject (nondiabetic woman with significant family history of DM), transcutaneous photobiomodulation (PBM) at various wavelengths was applied to the radial artery immediately after a standardized meal, or at the peak glucose after the standardized meal. Data were compared with a "no intervention" control period. Interstitial glucose was measured every 5 min until return to baseline. Results: A single transcutaneous application of PBM at wavelength and dose combinations tested and when applied immediately after a test meal or at peak glucose postprandially did not affect interstitial glucose levels in a woman without DM. Conclusions: Future studies could include testing additional subjects, using repeated PBM applications and monitoring using blood glucose.

Improvements in clinical signs of Parkinson's disease using photobiomodulation: a prospective proof-of-concept study.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. OBJECTIVE: To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). METHODS: Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12 weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14 weeks before commencing the same treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4 weeks of treatment, after 12 weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. RESULTS: Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved (p < 0.05) with PBM treatment for 12 weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. CONCLUSIONS: PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018.

Exploring the Effect of Combined Transcranial and Intra-Oral Photobiomodulation Therapy Over a Four-Week Period on Physical and Cognitive Outcome Measures for People with Parkinson's Disease: A Randomized Double-Blind Placebo-Controlled Pilot Study.

BACKGROUND: Neuroprotection against Parkinson's disease degeneration by photobiomodulation has been reported in animal models but no true placebo-controlled human studies have been published. OBJECTIVE: To understand if photobiomodulation therapy can produce clinically significant differences in physical performance measures in people with Parkinson's disease; and what frequency of treatment is necessary to initiate clinical change. METHODS: In a participant and assessor-blinded, randomized, placebo-controlled pilot study, 22 participants received either sham and/or active laser photobiomodulation (904 nm, 60 mW/diode, 50 Hz) for 33 s to each of 21 points at the cranium and intra-orally, on one, two or three times/week for 4 weeks. Two treatment phases were separated by a 4-week wash-out (Phase 2). Upper and lower limb physical outcome measures were assessed before and after each treatment phase. The Montreal Cognitive Assessment was evaluated prior to treatment Phase 1, and at the end of treatment Phase 3. RESULTS: Montreal Cognitive Assessment remained stable between start and end of study. No measures demonstrated statistically significant changes. With regular treatment, the spiral (writing) test and the dynamic step test were most sensitive to change in a positive direction; and the 9-hole peg test demonstrated a minimum clinically important difference worthy of further investigation in a larger, adequately powered clinical trial. A placebo effect was noted. CONCLUSION: The results support the notion that combined transcranial and intra-oral photobiomodulation therapy needs to be applied at least 2 to 3 times per week for at least four weeks before some improvement in outcome measures becomes evident. Longer courses of treatment may be required.

Pre-Conditioning and Post-Operative Photobiomodulation Therapy by a Novel Light Patch System for Knee Arthroplasty: A Protocol for a Phase 1 Study.

Objective: To determine the potential efficacy and feasibility of photobiomodulation therapy (PBMT) before and after knee arthroplasty (KA) surgery. Background: Total knee replacements (total knee arthroplasty, TKA) are one of the most common and successful surgical interventions for osteoarthritis. Up to 20,000 knee replacement arthroplasties are performed in Australia annually. Although TKA aims to restore knee alignment and relieve pain in the long term, the initial post-operative period is difficult and rehabilitation is often hindered by persistent pain and swelling. A promising therapeutic approach, PBMT using a novel self-adhesive light patch system, may be feasible for reducing post-operative pain and swelling and aiding recovery. Materials and methods: This is an interventional clinical feasibility study protocol. Patients from a surgical waitlist will be invited to take part. PBMT will be applied for 30 min daily for 7 days pre-operatively using a novel light patch system (CareWear®) with both 450 nm (6.75 mW/cm2) and 640 nm (2.25 mW/cm2) microdiodes. Post-operative treatment will utilize the same device second daily for 1 week after removal of compression bandages. Results: Outcomes will be evaluated at seven time points: baseline at week 1 pre-operatively, 1 day before surgery, day 4 after surgery, weekly for a further 2 weeks, and fortnightly until 6 weeks post-hospital discharge. Outcome measures include the following: Numeric Pain Rating Scale, stair climb test, 30-sec chair stand test, timed up and go test, 40-m fast-paced walk test, modified Iowa Level of Assistance Scale, muscle strength, knee range of motion, Knee Injury and Osteoarthritis Outcome Score, and Lower Limb Functional Index. Conclusions: This study will provide an assessment of feasibility of using PBMT applied using a novel light patch system for management of pain symptoms and swelling, and aiding recovery of patients undergoing TKA. The results of this feasibility study will contribute to planning of the design and methods of a large clinical trial.

Photobiomodulation (PBM) therapy at 904 nm mitigates effects of exercise-induced skeletal muscle fatigue in young women.

Muscle fatigue is a process influenced by several mechanisms such as concentration of metabolic substrates, changes in blood flow, and increases in reactive oxygen species that impair contractile muscle function. In this context, photobiomodulation has been investigated for preventing muscle fatigue, with reports of positive effects on muscle performance. This study aimed to investigate the effects of 904-nm LASER photobiomodulation on rectus femoris muscle performance in young women. Eighteen young women participated in a randomized, participant and assessor-blinded crossover trial with placebo control. Active LASER (904 nm, 60 mW, 250 Hz, 3.6 J per diode, total dose of 129.6 J) intervention was applied prior to an isokinetic fatigue protocol consisting of a set of 60 concentric quadricep contractions at a constant dynamometer angular velocity of 180°/s. Compared to placebo, LASER photobiomodulation significantly reduced muscle fatigue across a range of indicators including reduced ratings of perceived exertion (P = 0.0139), and increased electromyographic fatigue index (EFI) (P = 0.005). The isokinetic dynamometer performance analysis demonstrated that LASER photobiomodulation increased peak torque (P = 0.04), time to peak torque (P = 0.042), total work (P = 0.032), average power (P = 0.0007), and average peak torque (P = 0.019) between both experimental conditions. No significant difference was observed for work fatigue index (P = 0.29) or for lactate concentration (P > 0.05). Photobiomodulation at 904 nm was effective in reducing fatigue levels and increasing muscle performance in young active women but had no effect on lactate levels.

Effect of 830-nm laser phototherapy on olfactory neuronal ensheathing cells grown in vitro on novel bioscaffolds.

BACKGROUND: The purpose of this study was to analyze olfactory ensheathing cell (OEC) proliferation and growth on Biosilicate and collagen bioscaffolds, and to determine whether the application of laser phototherapy would result in increased OEC proliferation on the scaffolds. The use of bioscaffolds is considered a promising strategy in a number of clinical applications where tissue healing is suboptimal. As in vitro OEC growth is a slow process, laser phototherapy could be useful to stimulate proliferation on bioscaffolds. METHODS: OEC cells were seeded on the Biosilicate and collagen scaffolds. Seeded scaffolds were irradiated with a single exposure of 830-nm laser. Nonirradiated seeded scaffolds acted as negative controls. Cell proliferation was assessed 7 days after irradiation. RESULTS: OECs were successfully grown on discs composed of a glass-ceramic and collagen composite. Laser irradiation produced a 32.7% decrease and a 13.2% increase in OEC proliferation on glass-ceramic discs and on collagen scaffolds, respectively, compared with controls. Laser phototherapy resulted in a reduction in cell growth on the Biosilicate scaffolds and an increase in cell proliferation on collagen scaffolds. CONCLUSIONS: These results were probably due to the nature of the materials. Future research combining laser phototherapy and glass-ceramic scaffolds should take into account possible interactions of the laser with matrix compounds.

Inhibitory effects of laser irradiation on peripheral mammalian nerves and relevance to analgesic effects: a systematic review.

OBJECTIVE: The objective of this review was to systematically identify experimental studies of non-ablative laser irradiation (LI) on peripheral nerve morphology, physiology, and function. The findings were then evaluated with special reference to the neurophysiology of pain and implications for the analgesic effects of low-level laser therapy (LLLT). BACKGROUND: LLLT is used in the treatment of pain, and laser-induced neural inhibition has been proposed as a mechanism. To date, no study has systematically evaluated the effects of LI on peripheral nerve, other than those related to nerve repair, despite the fact that experimental studies of LI on nerves have been conducted over the past 25 years. METHODS: We searched computerized databases and reference lists for studies of LI effects on animal and human nerves using a priori inclusion and exclusion criteria. RESULTS: We identified 44 studies suitable for inclusion. In 13 of 18 human studies, pulsed or continuous wave visible and continuous wave infrared (IR) LI slowed conduction velocity (CV) and/or reduced the amplitude of compound action potentials (CAPs). In 26 animal experiments, IR LI suppressed electrically and noxiously evoked action potentials including pro-inflammatory mediators. Disruption of microtubule arrays and fast axonal flow may underpin neural inhibition. CONCLUSIONS: This review has identified a range of laser-induced inhibitory effects in diverse peripheral nerve models, which may reduce acute pain by direct inhibition of peripheral nociceptors. In chronic pain, spinal cord changes induced by LI may result in long-term depression of pain. Incomplete reporting of parameters limited aggregation of data.

The effect of laser irradiation on proliferation of human breast carcinoma, melanoma, and immortalized mammary epithelial cells.

OBJECTIVE: This study compared the effects of different doses (J/cm(2)) of laser phototherapy at wavelengths of either 780, 830, or 904 nm on human breast carcinoma, melanoma, and immortalized human mammary epithelial cell lines in vitro. In addition, we examined whether laser irradiation would malignantly transform the murine fibroblast NIH3T3 cell line. BACKGROUND: Laser phototherapy is used in the clinical treatment of breast cancer-related lymphoedema, despite limited safety information. This study contributes to systematically developing guidelines for the safe use of laser in breast cancer-related lymphoedema. METHODS: Human breast adenocarcinoma (MCF-7), human breast ductal carcinoma with melanomic genotypic traits (MDA-MB-435S), and immortalized human mammary epithelial (SVCT and Bre80hTERT) cell lines were irradiated with a single exposure of laser. MCF-7 cells were further irradiated with two and three exposures of each laser wavelength. Cell proliferation was assessed 24 h after irradiation. RESULTS: Although certain doses of laser increased MCF-7 cell proliferation, multiple exposures had either no effect or showed negative dose response relationships. No sign of malignant transformation of cells by laser phototherapy was detected under the conditions applied here. CONCLUSION: Before a definitive conclusion can be made regarding the safety of laser for breast cancer-related lymphoedema, further in vivo research is required.

Nociceptive scores and endorphin-containing cells reduced by low-level laser therapy (LLLT) in inflamed paws of Wistar rat.

OBJECTIVE: This study aimed to investigate how local pain relief is mediated by laser therapy and how dose affects the relationship. METHODS: Inflammation was induced in the hind-paws of Wistar rats. Two groups of rats received 780-nm laser therapy (Spectra-Medics Pty Ltd.) at one of two doses (2.5 and 1 J/cm(2)). One group acted as a control. Scores of nociceptive threshold were recorded using paw pressure and paw thermal threshold measures. RESULTS: A dose of 1 J/cm(2) had no statistically significant effect on antinociceptive responses. A dose of 2.5 J/cm(2) demonstrated a statistically significant effect on paw pressure threshold ( p < 0.029) compared to controls. There was no difference in paw thermal threshold responses and paw volumes at either dose. Immunohistochemistry in control animals demonstrated normal beta-endorphin containing lymphocytes in control inflamed paws but no beta-endorphin containing lymphocytes in rats that received laser at 2.5 J/cm(2). CONCLUSION: The results confirm previous findings that the effect of laser therapy is dose-related. The mechanism of effect may occur via a differentiated pressure-sensitive neural pathway rather than a thermal-sensitive neural pathway. The significance of the immunohistochemistry findings remains unknown.