Histochemical mapping of the duration of action of photobiomodulation on cytochrome c oxidase in the rat brain.

Introduction: This is the first study mapping the duration of action of in vivo photobiomodulation (PBM) on cytochrome-c-oxidase (CCO). In cellular bioenergetics, CCO is the terminal rate-limiting enzyme in the mitochondrial electron transport chain, which catalyzes oxygen utilization for aerobic energy production. PBM using transcranial infrared laser stimulation (TILS) is a promising intervention for non-invasively modulating CCO in the brain. TILS of the human prefrontal cortex directly causes CCO photo-oxidation, which is associated with increased cerebral oxygenation and improved cognition. Methods: This experiment aimed to map the duration of action of in vivo PBM on CCO activity in discrete neuroanatomic locations within rat brains up to 4 weeks after a single TILS session (50 s, 1064 nm CW, 250 mW/cm2). Control brains from rats treated with a sham session without TILS (laser off) were compared to brains from TILS-treated rats that were collected 1 day, 2 weeks, or 4 weeks post-TILS. Cryostat sections of the 36 collected brains were processed using quantitative enzyme histochemistry and digitally imaged. Densitometric readings of 28 regions of interest were recorded and converted to CCO activity units of oxygen utilization using calibration standards. Data analysis (ANCOVA) compared each laser-treated group to sham with whole-brain average as a covariate. Results: The prefrontal infralimbic cortex showed the earliest significant increase in CCO activity between 1-day post-TILS and sham groups, which continued elevated for 2-4 weeks post-TILS. Significant differences in CCO activity between 2-weeks and sham groups were also found in the lateral septum, accumbens core, CA3 of the hippocampus, and the molecular layer of the hippocampus. The medial amygdala showed a significant decrease in CCO activity between 4-weeks and sham. Further analyses showed significant inter-regional CCO activity correlations among the brain regions as the result of TILS, with the most pronounced changes at 4-weeks post-stimulation. Discussion: The time course of changes in CCO activity and network connectivity suggested that TILS caused different neuroplasticity types of bioenergetic changes at different time scales, depending on brain region and its depth from the cortex. In conclusion, this controlled CCO histochemical study demonstrated a long-lasting duration of action of PBM in the rat brain.

Painful Cutaneous Laser Stimulation for Temporal Summation of Pain Assessment.

Variability in pain sensitivity arises not only from the differences in peripheral sensory receptors but also from the differences in central nervous system (CNS) pain inhibition and facilitation mechanisms. Temporal summation of pain (TSP) is an experimental protocol commonly used in human studies of pain facilitation but is susceptible to confounding when elicited with the skin-contact thermode, which adds the responses of touch-related Aß low-threshold mechanoreceptors to nociceptive receptors. In the present study, we evaluate an alternative method involving the use of a contactless cutaneous laser for TSP assessment. We show that repetitive laser stimulations with a one second inter-stimulus interval evoked reliable TSP responses in a significant proportion of healthy subjects (N = 36). Female subjects (N = 18) reported greater TSP responses than male subjects confirming earlier studies of sex differences in central nociceptive excitability. Furthermore, repetitive laser stimulations during TSP induction elicited increased time-frequency electroencephalography (EEG) responses. The present study demonstrates that repetitive laser stimulation may be an alternative to skin-contact methods for TSP assessment in patients and healthy controls. PERSPECTIVE: Temporal summation of pain (TSP) is an experimental protocol commonly used in human studies of pain facilitation. We show that contactless cutaneous laser stimulation is a reliable alternative to the skin contact approaches during TSP assessment.

Photobiomodulation in Alzheimer's Disease-A Complementary Method to State-of-the-Art Pharmaceutical Formulations and Nanomedicine?

Alzheimer's disease (AD), as a neurodegenerative disorder, usually develops slowly but gradually worsens. It accounts for approximately 70% of dementia cases worldwide, and is recognized by WHO as a public health priority. Being a multifactorial disease, the origins of AD are not satisfactorily understood. Despite huge medical expenditures and attempts to discover new pharmaceuticals or nanomedicines in recent years, there is no cure for AD and not many successful treatments are available. The current review supports introspection on the latest scientific results from the specialized literature regarding the molecular and cellular mechanisms of brain photobiomodulation, as a complementary method with implications in AD. State-of-the-art pharmaceutical formulations, development of new nanoscale materials, bionanoformulations in current applications and perspectives in AD are highlighted. Another goal of this review was to discover and to speed transition to completely new paradigms for the multi-target management of AD, to facilitate brain remodeling through new therapeutic models and high-tech medical applications with light or lasers in the integrative nanomedicine of the future. In conclusion, new insights from this interdisciplinary approach, including the latest results from photobiomodulation (PBM) applied in human clinical trials, combined with the latest nanoscale drug delivery systems to easily overcome protective brain barriers, could open new avenues to rejuvenate our central nervous system, the most fascinating and complex organ. Picosecond transcranial laser stimulation could be successfully used to cross the blood-brain barrier together with the latest nanotechnologies, nanomedicines and drug delivery systems in AD therapy. Original, smart and targeted multifunctional solutions and new nanodrugs may soon be developed to treat AD.

A novel temperature-controlled laser system to uniformly activate cutaneous thermal receptors during movable thermal stimulation.

Objective. Laser stimulators have been widely used in pain studies to selectively activate Aδand C nociceptors without coactivation of mechanoreceptors. Temperature-controlled laser systems have been implemented with low-temperature variations during stimulations, however, these systems purely enabled stationary stimulation. This study aimed to implement, test and validate a new laser stimulation system that controls skin temperature by continuously adjusting laser output during stimulus movement to allow accurate investigation of tempo-spatial mechanisms in the nociceptive system.Approach. For validation, laser stimuli were delivered to the right forearm of eight healthy subjects using a diode laser. The laser beam was displaced across the skin to deliver a moving thermal stimulation to the skin surface. To test the function and feasibility of the system, different stimulation parameters were investigated involving two control modes (open-loop and closed-loop), three displacement velocities (5, 10 and 12 mm s-1), two intensities (high 46 °C and low 42 °C), two stimulus lengths (20 and 100 mm) and two directions (distal and proximal).Main results. During closed-loop control, the stimulation error and variation of stimulation temperatures were significantly smaller than during open-loop control. The standard deviation of stimulation temperatures increased significantly with stimulation intensity and displacement length.Significance. This study showed that more accurate, less variable laser stimulations were delivered to the skin using closed-loop control during a movable stimulus. The more uniform skin temperature during stimuli is likely to ensure a more uniform nociceptor activation.

Metallic 4D Printing of Laser Stimulation.

4D printing of metallic shape-morphing systems can be applied in many fields, including aerospace, smart manufacturing, naval equipment, and biomedical engineering. The existing forming materials for metallic 4D printing are still very limited except shape memory alloys. Herein, a 4D printing method to endow non-shape-memory metallic materials with active properties is presented, which could overcome the shape-forming limitation of traditional material processing technologies. The thermal stress spatial control of 316L stainless steel forming parts is achieved by programming the processing parameters during a laser powder bed fusion (LPBF) process. The printed parts can realize the shape changing of selected areas during or after forming process owing to stress release generated. It is demonstrated that complex metallic shape-morphing structures can be manufactured by this method. The principles of printing parameters programmed and thermal stress pre-set are also applicable to other thermoforming materials and additive manufacturing processes, which can expand not only the materials used for 4D printing but also the applications of 4D printing technologies.

Singular and combined effects of transcranial infrared laser stimulation and exposure therapy on pathological fear: a randomized clinical trial.

BACKGROUND: Preclinical findings suggest that transcranial infrared laser stimulation (TILS) improves fear extinction learning and cognitive function by enhancing prefrontal cortex (PFC) oxygen metabolism. These findings prompted our investigation of treating pathological fear using this non-invasive stimulation approach either alone to the dorsolateral PFC (dlPFC), or to the ventromedial PFC (vmPFC) in combination with exposure therapy. METHODS: Volunteers with pathological fear of either enclosed spaces, contamination, public speaking, or anxiety-related bodily sensations were recruited for this randomized, single-blind, sham-controlled trial with four arms: (a) Exposure + TILS_vmPFC (n = 29), (b) Exposure + sham TILS_vmPFC (n = 29), (c) TILS_dlPFC alone (n = 26), or (d) Sham TILS _dlPFC alone (n = 28). Post-treatment assessments occurred immediately following treatment. Follow-up assessments occurred 2 weeks after treatment. RESULTS: A total of 112 participants were randomized [age range: 18-63 years; 96 females (85.71%)]. Significant interactions of Group × Time and Group × Context indicated differential treatment effects on retention (i.e. between time-points, averaged across contexts) and on generalization (i.e. between contexts, averaged across time-points), respectively. Among the monotherapies, TILS_dlPFC outperformed SHAM_dlPFC in the initial context, b = -13.44, 95% CI (-25.73 to -1.15), p = 0.03. Among the combined treatments, differences between EX + TILS_vmPFC and EX + SHAM_vmPFC were non-significant across all contrasts. CONCLUSIONS: TILS to the dlPFC, one of the PFC regions implicated in emotion regulation, resulted in a context-specific benefit as a monotherapy for reducing fear. Contrary to prediction, TILS to the vmPFC, a region implicated in fear extinction memory consolidation, did not enhance exposure therapy outcome.

An Initial Study on Multi-Point Laser Acupuncture Based on 2-D Galvo Mirror.

Currently, the majority of commercially available laser acupuncture instruments are still hand-held and only support single-point stimulation. Simultaneous multi-point stimulation improves the therapeutic efficacy of laser acupuncture by stimulating multiple acupoints at the same time. A "2-dimensional (2-D) galvo mirror" was utilized as a positioning laser acupuncture device for multi-acupoints stimulation. Due to its ability to perform 2-D fast scanning, a single laser beam was reflected by the mirror and stimulated multiple acupuncture points simultaneously. This introduction to the new system, presents its architecture, and shows some initial results. This initial stage of development was focused on the acupoints of the human forearm. This proposed system is the first low-cost, noncontact laser acupuncture system that enables continuous multi-acupoint stimulation with a single laser beam. Notably, it is technically feasible to develop this technique into a whole-body laser acupuncture stimulation system.

Activation of Mitochondrial Ca 2+ Oscillation and Mitophagy Induction by Femtosecond Laser Photostimulation.

Ultra-precise stimulation solely to individual mitochondria, without any influence to the whole cell, is quite difficult by traditional biochemical reagents. In mitophagy research, the mitochondria and even the whole cell usually suffer irreversible and great damage caused by treatment with potent chemicals. In this protocol, we present the technical procedures of our developed noninvasive ultra- precise laser stimulation (UPLaS) technology, which introduces precise stimulation to individual mitochondria, to excite mitochondrial Ca 2+ (mitoCa 2+ ) oscillations, with little perturbation to mitochondrial membrane potential (MMP), or mitochondrial reactive oxygen species (mitoROS). The mitoCa 2+ oscillation by UPLaS was able to initiate the PINK1/Parkin pathway for mitophagy. This protocol has good potential to benefit researches on mitophagy and mitochondrial diseases. Graphic abstract: Figure 1.Flowchart of the UPLaS technology.The femtosecond laser (1030 nm, 1 MHz, 220 fs) can stimulate individual mitochondria (1 µm 2 ) for a short period (0.1 s), whereas confocal microscopy (CM) provides continuous cell imaging to monitor molecular dynamics in real time, before and after UPLaS.

The Future of Laser Acupuncture-Robot-Assisted Laser Stimulation and Evaluation.

This brief contribution is part of a Special Issue entitled 'Laser Acupuncture: Past, Present and Future' and primarily deals with the future of laser acupuncture from the author's perspective. The procedure from developing the first laser to robot-assisted laser acupuncture is briefly shown. The latter has already become a reality and, in the near future, will be made accessible to a broad group of patients as a home treatment system developed by researchers from Taiwan. The new equipment is based on a smartphone with integrated artificial intelligence methods (e.g., automatic image recognition).

Transcranial Infrared Laser Stimulation for the Treatment of Traumatic Brain Injury: A Case Series.

Introduction: This study intended to evaluate the safety and possible therapeutic effect of transcranial infrared laser stimulation (TILS) based on photobiomodulation (PBM) among patients with traumatic brain injury (TBI). Methods: Eleven participants who were diagnosed with TBI after full neurological examination and MRI evaluation by a board-certified neurologist completed five to eight 20-minute TILS sessions using the Cytonsys CytonPro-5000 apparatus (pilot laser control, focused wavelength of 1064 nm, maximum output power of 10W, maximum optical power density of 500 mW/cm2, effective area 4.5 cm2 in diameter). Per TILS session, participants underwent a laser dose of 250 mW/cm2 continuous laser wave to each hemisphere using predetermined patient-specific coordinates. Structural imaging was used to neuronavigate individual treatment targets in the frontal cortex (Brodmann area 10). The primary safety measure for this study was the occurrence of adverse events (AEs) or serious adverse events (SAEs). The primary efficacy outcome measure was the participant-rated global rating of change (GRC) post-intervention. Secondary outcome measures included a battery of neuropsychological testing and mood questionnaires done both pre- and post-intervention. Results: All patients enrolled in this study protocol were able to tolerate the study procedures without any AEs or SAEs. Nine out of eleven participants had clinically significant improvements in GRC score (≥ +2). Neuropsychological testing and mood questionnaire outcomes also suggested a positive therapeutic effect. Conclusion: This study provides preliminary evidence supporting the safety and potential efficacy of TILS as a non-invasive clinical intervention for individuals with TBI.

The two-point discrimination threshold depends both on the stimulation noxiousness and modality.

The two-point discrimination threshold (2PDT) has been used to investigate the integration of sensory information, especially in relation to spatial acuity. The 2PDT has been investigated for both innocuous mechanical stimuli and noxious thermal stimuli; however, previous studies used different stimulation modalities to compare innocuous and noxious stimuli. This study investigated the 2PDT in 19 healthy participants, using both thermal (laser) and mechanical stimulation modalities. Within each modality, both innocuous and noxious intensities were applied. Concurrent point stimuli were applied to the right volar forearm, with separation distances of 0-120 mm, in steps of 10 mm. 0 mm corresponds to a single point. Following each stimulus, the participants indicated the number of perceived points (1 or 2) and the perceived intensity (NRS: 0: no perception, 3: pain threshold, 10: maximum pain). The order of stimulation modality, intensity and distance was randomized. The 2PDT for innocuous and noxious mechanical stimuli was 34.7 mm and 47.1 mm, respectively. For thermal stimuli, the 2PDT was 80.5 mm for innocuous stimuli and 66.9 mm for noxious stimuli. The average NRS for thermal stimuli was 1.6 for innocuous intensities and 4.0 for noxious intensities, while for mechanical stimuli, the average NRS was 0.9 for innocuous intensities and 3.6 for noxious intensities. This study showed that the 2PDT highly depends on both stimulation modality and intensity. Within each modality, noxious intensities modulates the 2PDT differently, i.e., noxious intensities lowers the 2PDT for thermal stimuli, but increases the 2PDT for mechanical stimuli.

Transcranial laser stimulation: Mitochondrial and cerebrovascular effects in younger and older healthy adults.

BACKGROUND: Transcranial laser stimulation is a novel method of noninvasive brain stimulation found safe and effective for improving prefrontal cortex neurocognitive functions in healthy young adults. This method is different from electric and magnetic stimulation because it causes the photonic oxidation of cytochrome-c-oxidase, the rate-limiting enzyme for oxygen consumption and the major intracellular acceptor of photons from near-infrared light. This photobiomodulation effect promotes mitochondrial respiration, cerebrovascular oxygenation and neurocognitive function. Pilot studies suggest that transcranial photobiomodulation may also induce beneficial effects in aging individuals. OBJECTIVES: Randomized, sham-controlled study to test photobiomodulation effects caused by laser stimulation on cytochrome-c-oxidase oxidation and hemoglobin oxygenation in the prefrontal cortex of 68 healthy younger and older adults, ages 18-85. METHODS: Broadband near-infrared spectroscopy was used for the noninvasive quantification of bilateral cortical changes in oxidized cytochrome-c-oxidase and hemoglobin oxygenation before, during and after 1064-nm wavelength laser (IR-A laser, area: 13.6 cm2, power density: 250 mW/cm2) or sham stimulation of the right anterior prefrontal cortex (Brodmann Area 10). RESULTS: As compared to sham control, there was a significant laser-induced increase in oxidized cytochrome-c-oxidase during laser stimulation, followed by a significant post-stimulation increase in oxygenated hemoglobin and a decrease in deoxygenated hemoglobin. Furthermore, there was a greater laser-induced effect on cytochrome-c-oxidase with increasing age, while laser-induced effects on cerebral hemodynamics decreased with increasing age. No adverse laser effects were found. CONCLUSION: The findings support the use of transcranial photobiomodulation for cerebral oxygenation and alleviation of age-related decline in mitochondrial respiration. They justify further research on its therapeutic potential in neurologic and psychiatric diseases.

The effects of laser stimulation at acupoint ST36 on anxiety-like behaviors and anterior cingulate cortex c-Fos expression in a rat post-traumatic stress disorder model.

Post-traumatic stress disorder (PTSD) is a mental disorder that is linked with the onset of multiple anxiety-like behaviors. This study was designed to assess how these behaviors and anterior cingulate cortex (ACC) c-Fos expression were impacted by 10.6-µm laser stimulation at acupoint ST36 a rat model of PTSD. A rat model of PTSD was prepared via prolonged exposure of animals to a stressor, followed by a 7-day period during which animals were allowed to rest undisturbed in their cages. Rats were randomized into four experimental groups (n = 12/group): the control, PTSD, LS, and sham LS groups. Control group animals were not subjected to SPS procedures prior to behavioral testing. LS and sham LS animals were administered LS treatment at bilateral ST36 acupoints or non-acupoints, respectively, for a 7-day period. Animals were then assessed for performance in elevated plus maze (EPM) tests and open-field tests (OFT), and their plasma corticosterone levels were measured. In addition, c-Fos-positive nuclei in the ACC were detected via immunohistochemical staining. Relative to sham LS treatment and PTSD model control rats, LS was associated with increased time spent in both open EPM test arms and in the central area in the OFT (P < 0.05). The PTSD model group exhibited a significant reduction in ACC c-Fox expression, while LS treatment significantly increased this expression (P < 0.001). In addition, a correlation was detected between anxiety-like behaviors and altered ACC neuronal activation. The results of this study indicate that LS at acupoint ST36 can have a previously unreported effect on anxiety-like behaviors in the context of PTSD, with ACC neuronal activation potentially being implicated as a driver of this effect.

Optogenetic Stimulation of the Central Amygdala Using Channelrhodopsin.

Optogenetics allows for the targeted temporary inhibition or stimulation of specific brain regions in vivo with precise temporal resolution. Here, we describe the steps to perform intracranial optogenetic surgery in rodents as well as instructions to build an optogenetic headcap and set up an optogenetic testing environment to conduct experiments. Behavioral studies have implemented these methods to stimulate the central amygdala (CeA) to create an addictive-like preference for reward.

New Insights into Cutaneous Laser Stimulation - Dependency on Skin and Laser Type.

Cutaneous laser stimulation is a proficient tool to investigate the function of the nociceptive system. However, variations in laser-skin interactions, causes by different skin anatomies and laser wavelength, affects the robustness of nociceptor activation. Thus, thoroughly understanding how the skin is heated by a laser pulse is important to characterize the thermal response properties of nociceptors. The study aim was to investigate how skin type and laser wavelength influences nociceptor activation during laser stimulation. Ten healthy subjects were exposed to brief CO2 (low skin penetrance) and Nd:YAP (high skin penetrance) laser stimuli delivered to the dorsum and palm of the hand, using three different intensities. Reaction times and perception intensities were recorded. A computational model simulated heat transfer in the skin and nociceptor activation in different skin types across different wavelengths and intensities. Intensity ratings were significantly lower and reaction-times significantly increased for CO2 laser stimuli in the palm compared to the dorsum. This was not the case for Nd:YAP laser stimuli. The computational model showed that these differences can be explained by the different skin absorption of CO2 and Nd:YAP lasers. For CO2 laser stimuli, the thicker stratum corneum of the glabrous skin reduces nociceptor activation, whereas the high penetrating Nd:YAP laser elicits a similar nociceptor activation, irrespective of skin type. Nociceptor activation during laser stimulation highly depends on skin composition and laser wavelength, especially for lasers having a low penetrance wavelength. A computational model showed that this difference could be explained primarily due to differences in skin composition.

Approach Behavior Induced by 10.6-µm Laser Stimulation at Acupoint ST36 in a Rat Model of Incisional Pain.

Objective: Laser stimulation (LS) at both the injury site and specific acupoints may induce analgesic effects. The purpose of this study is to investigate the effects of LS at injury site or acupoint on analgesic-associated approach behavior and determine whether opioid receptors in the anterior cingulate cortex (ACC) were involved. Methods: The left hindpaw incision was established in rats. LS (10.6 µm) was performed at the ipsilateral (left) acupoint ST36 (Zusanli) or locally to the incision site. Characteristic guarding pain behavior was measured to assess incision-induced pain. A two-chamber conditioned place preference (CPP) paradigm was used to measure approach behavior induced by pain relief. To inhibit opioid receptors, naloxone was microinjected into the ACC before LS. Results: A delayed analgesic effect (24 h after treatment) was induced in both the LS groups (ST36 and incision site) as compared with the sham control or model groups (p < 0.05). An immediate (30 min after the end of the LS) decrease in guarding pain (p < 0.001) and CPP for the LS chamber (p < 0.001) were observed only in the ST36 LS group. The administration of naloxone in ACC inhibited the LS-induced analgesic effect and CPP (p < 0.05). Conclusions: Our results highlight the novel approach behavior of pain relief induced by 10.6-µm LS at ST36 in a rat model of incisional pain, and implicate ACC opioid receptor signaling in these actions.

Directional discrimination is better for noxious laser stimuli than for innocuous laser stimuli.

BACKGROUND: The directional discrimination is lower for painful laser heat compared to non-painful mechanical stimulation. The aim of the current study was to investigate how the directional discrimination of radiant heat stimulation depends on stimulation intensity and displacement velocity. METHODS: Fifteen healthy subjects were stimulated in the right volar forearm with a CO2 laser at intensities that were expected to be either painful (46°C) or non-painful (39°C). The laser beam was continuously displaced distal-proximally along the arm during the stimulation. After the stimulation, subjects indicated the perceived direction and intensity (NRS: 0: perception 3: pain 10: maximum pain). Stimulations were delivered with five lengths (20, 40, 60, 80 and 100 mm) and three velocities (10, 30 and 100 mm/s). To estimate the directional discrimination threshold (DDT) the data were fitted to a sigmoidal curve. RESULTS: For the lower intensity (39°C) the DDT was 81.8 mm for the slowest velocity, and above 100 mm for the two faster velocities. For the higher intensity (46°C) the DDT was 58.8 and 69.6 mm for the slowest velocity and middle velocity, respectively, and above 100 mm for the fastest velocity. The perceived intensity increased with stimulation length, stimulation intensity and decreasing velocity (LMM, p < .001). CONCLUSIONS: This study shows how the DDT for thermal stimuli is shorter for higher intensity and lower displacement velocities. Additionally, it was shown that for the velocity where directional discrimination is optimal for mechanical stimuli it is not possible to discriminate a thermal stimulus. SIGNIFICANCE: This study showed that the directional discrimination of painful laser stimuli is better than that for non-painful laser stimuli. These findings supplements our current knowledge regarding the tempo-spatial discrimination in the nociceptive system, where evidence from previous discrimination studies differs somewhat regarding difference between painful and non-painful discrimination. This, therefore, indicates that there is lacking knowledge regarding the discrimination within the nociceptive system.

Cutaneous nociceptive sensitization affects the directional discrimination - but not the 2-point discrimination.

Background and aims Several pain conditions have been shown to reduce the discriminative abilities of external stimuli. The aim of this study was to investigate how cutaneous sensitization affects the tempo-spatial discrimination for both painful laser stimulation and mechanical stimulation. Methods Fifteen healthy subjects were presented with two different stimulation paradigms, a continuous line stimulation and a 2-point stimulation. Line stimulations were delivered in two different directions in lengths of 25, 50, 75, and 100 mm. Two-point distances from 0 to 100 mm were tested. The subjects reported the perceived intensity, and either direction (line stimulations) or number of perceived points (2-point stimulations). All stimuli were tested both before and after topical capsaicin (8% concentration) sensitization (30 min). Results All mechanical line stimulations were reported correctly before capsaicin and 3 stimulations (out of 240) were reported incorrectly after capsaicin. For the laser line stimulation, the directional discrimination threshold (DDT) was 69.5 mm before capsaicin and 76.3 mm after capsaicin. The 2-point discrimination threshold for laser stimulation was 70.3 mm before capsaicin and 68.0 mm after, for the mechanical stimuli it was 31.5 mm before capsaicin and 31.0 mm after capsaicin. The perceived intensities were increased for the laser line stimulations after capsaicin (linear mixed model (LMM), p < 0.001) and increased with stimulation length (LMM, p < 0.001). For mechanical stimuli, NRS was increased following capsaicin (LMM, p < 0.001). The intensities for both mechanical and laser 2-point stimuli increased after capsaicin and increased with distance between points (LMM, p < 0.01). Conclusions The findings show how cutaneous sensitization appears to affect directional discrimination to a larger extent than the 2-point discrimination. Implications This study is the first to investigate how directional discrimination is altered during sensitization. If such measures can be optimized they may provide a new method to probe the neural mechanisms in pain patients.

Which wavelength is optimal for transcranial low-level laser stimulation?

One of the challenges in transcranial low-level laser therapy (LLLT) is to optimally choose illumination parameters, such as wavelength. However, there is sparse study on the wavelengths comparison especially on human transcranial LLLT. Here, we employed Monte Carlo modeling and visible human phantom to compute the penetrated photon fluence distribution within cerebral cortex. By comparing the fluence distribution, penetration depth and the intensity of laser-tissue-interaction within brain among all candidate wavelengths, we found that 660, 810 nm performed much better than 980, 1064 nm with much stronger, deeper and wider photon penetration into cerebral tissue; 660 nm was shown to be the best and slightly better than 810 nm. Our computational finding was in a surprising accordance with previous LLLT-neurobehavioral studies on mice. This study not only offered quantitative comparison among wavelengths in the effect of LLLT light penetration effectiveness but also anticipated a delightful possibility of online, precise and visible optimization of LLLT illumination parameters.

Multimodal Laser Stimulation and Traditional Needle Acupuncture in Post-Stroke Patients-A Pilot Cross-Over Study with Results from Near Infrared Spectroscopy.

Background: The objective of this pilot study was to evaluate the cerebral effects of laser stimulation and traditional needle acupuncture in patients after stroke. Methods: Seventeen stroke patients (12 female and five male; mean age ± SD: 66.5 ± 12.9 years) were randomly selected in a stroke rehabilitation hospital. Patients' regional cerebral blood oxygen saturation (rSO2) values were recorded before, during, and after needle acupuncture (scalp, ear and body) as well as before, during, and after corresponding laser stimulation (red laser, four points: 100 mW, 658 nm, 500 µm; yellow laser, one point: 50 mW, 589 nm, 500 µm; infrared laser, three points: 100 mW, 810 nm, 500 µm; green laser, one point: 5 mW, 532 nm, 500 µm) in a cross-over study design. Results: There were no significant changes after needle acupuncture in the phases immediately after needle insertion or during acupuncture stimulation. However, after manual needle acupuncture and after laser stimulation, the majority of the rSO2 values showed increases. The highest value (+3%) was reached after laser stimulation treatment. Heart rate and blood pressure before and after the treatments did not show significant alterations. Conclusions: Changes in local cerebral oxygen saturation could be quantified, although confirmation may only be expected after extensive follow-up studies.