Effectiveness of photobiomodulation therapy in the treatment of patients with an ankle sprain: a systematic review and meta-analysis.

BACKGROUND: Photobiomodulation therapy (PBMT) is widely used in the treatment of patients with musculoskeletal and sports disorders with a lack of significance in patients with sprain ankle. PURPOSE: This review investigated the effect of PBMT on pain, oedema, and function in patients with an ankle sprain. METHODS: A systematic search of the databases (MEDLINE, PubMed, EBSCO, Web of Science, Wiley Online Library, Science Direct, Physiotherapy Evidence (PEDro), and the Cochrane Databases) was performed from inception to the end of 2023 to identify any clinical study investigating the effect of PBMT on ankle sprain. PBMT parameters and measured outcomes were extracted. The primary measured outcome was pain and function, and oedema were secondary measured outcomes. Methodological quality was assessed using the PEDro scale. The level of evidence was determined by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. A random effect meta-analysis with forest plot was used to calculate standardized mean difference (SMD) at a 95% confidence interval and the overall effect size (ES). RESULTS: Six studies (598 patients) were included in the review and five studies in the meta-analysis. There were two fair-quality and four good-quality studies, with a moderate level of evidence on pain, and a low level of evidence on oedema and function. The meta-analysis revealed a significant overall effect of PBMT on pain with high ES [SMD - 0.88 (-1.76, -0.00), p = 0.05], with a non-significant effect on oedema and function with a medium ES [SMD - 0.70 (-1.64, 0.24), p = 0.14] on oedema and low ES on function [SMD - 0.22 (-0.69, 0.24), p = 0.35]. Significant heterogeneity was observed in all measured outcomes with high heterogeneity (I2 > 75%) in pain and oedema and moderate heterogeneity in function. CONCLUSION: PBMT is quite effective for patients with an ankle sprain. PBMT showed high effect size with a moderate level of evidence on pain intensity. The lack of significant effects of PBMT on function and edema with low level of evidence limit the confidence to the current results and recommend further large high-quality studies with higher PBMT intensity and fluency for standardisation of the irradiation parameters and treatment protocol. REGISTRATION: PROSPERO registration number (CRD42021292930).

Evaluation of the therapeutic effects of led (λ627 ± 10 nm) on the initial phase of ankle sprain treatment: a randomised placebo-controlled clinical trial.

Various therapies for the treatment of sprains have emerged as advances occur in biomedical engineering and photobiology. Therapy with coherent and non-coherent light is a treatment modality for various musculoskeletal injuries. The main certified phototherapy benefits are the reduction of nociceptive processes and the modulation of the inflammatory process, among others. The objective of this study was to analyse the changes caused by the use of light-emitting diodes (LED) (λ627 ± 10 nm) with an energy density of 10 J/cm2 in 40 subjects divided into two groups (20 placebo and 20 LED). All of the volunteers had acute ankle sprains by inversion of grade II treated with the PRICE (protection, rest, ice, compression and elevation) technique and were treated for 6 days with LED therapy and LED therapy turned off (placebo). Pain assessment was performed on the 1st, 3rd and 6th days using the visual analogue scale (VAS) of pain, the McGill Pain Questionnaire and volumetry. The group treated with LED showed statistically decreased pain compared to the placebo group in both the VAS (85.79 vs 55.73%) and McGill questionnaire (83.33 vs 52.52%). The reduction of oedema in the LED group on the 3rd and 6th days after therapy was statistically superior to that in the placebo (p < 0.0001). Based on the results of this study, treatment with LED, using the tested dose, is effective for pain and oedema in the initial phase of ankle sprains.

Is Low-Level Laser Therapy Effective in the Management of Pain and Swelling After Mandibular Third Molar Surgery?

PURPOSE: This study evaluated the effect of low-level laser therapy (LLLT) on decreasing pain and swelling after removal of impacted third molars. PATIENTS AND METHODS: This randomized, double-blinded, split-mouth study included patients presenting 2 symmetrically impacted mandibular third molars. In each participant, one side was randomly assigned to laser treatment and the other side received placebo. LLLT was performed by intraoral application of a 660-nm laser (200 mW, 6 J per point at 4 points) followed by extraoral application of an 810-nm laser (200 mW, 6 J per point at 3 points). Irradiation at the 810-nm wavelength was repeated on days 2 and 4 after surgery. On the control side, the treatment protocol was similar to the experimental side, but with laser simulation. The main outcomes were the degree of pain during the next 7 days and the edema coefficients on days 2, 4, and 7 after surgery. Data were analyzed using generalized linear models to determine the effect of group and time on pain level and edema coefficients. RESULTS: The final sample consisted of 40 patients. Pain level was significantly lower in the laser than in the placebo side at all time points during the experiment (P < .05). Swelling was significantly lower in the laser than in the placebo group on days 2, 4, and 7 after surgery (P < .05). CONCLUSION: LLLT proved effective in decreasing the intensity of pain and swelling after removal of impacted third molars and can be recommended to alleviate patients' symptoms after surgery.

Expression of mPGES-1 and IP mRNA is reduced by LLLT in both subplantar and brain tissues in the model of peripheral inflammation induced by carrageenan.

The increase in PGE2 production by microsomal PGE synthase-1 (mPGES-1) in CNS contributes to the severity of the inflammatory and pain responses in the model of edema formation and hyperalgesia induced by carrageenan. PGI2, alike to PGE2, plays an important role in the inflammation. Low-level laser therapy (LLLT) has been used in the treatment of inflammatory pathologies, reducing both pain and the acute inflammatory process. In this work, we studied the effect of LLLT on the expression of both mPGES-1 and IP messenger RNA (mRNA), in either subplantar or total brain tissues obtained from rats submitted to model of edema formation and hyperalgesia induced by carrageenan administration. The test sample consisted of 30 rats divided into five groups: A1 (control-saline), A2 (carrageenan-0.5 mg/paw), A3 (carrageenan-0.5 mg/paw + LLLT), A4 (carrageenan-1.0 mg/paw), and A5 (carrageenan-1.0 mg/paw + LLLT). The animals from groups A3 and A5 were irradiated 1 h after induction of inflammation by carrageenan injection. Continuous-wave red laser with wavelengths of 660 nm and dose of 7.5 J/cm(2) was used. Six hours after carrageenan-induced inflammation, mPGES-1 and prostacyclin receptor (IP) mRNA expression were significantly increased both in subplantar and brain tissues. LLLT was able to reduce both mPGES-1 and IP mRNA expression in subplantar and brain tissues. We suggest that LLLT is able to reduce both inflammation and hyperalgesia observed in the model of edema formation and hyperalgesia induced by carrageenan, by a mechanism involving the decrease in the expression of both mPGES-1 and IP.

Photobiostimulation reduces edema formation induced in mice by Lys-49 phospholipases A2 isolated from Bothrops moojeni venom.

The prominent local myotoxic effects induced by Bothrops snake venom are due, in part, to myotoxins. This effect is not neutralized by antivenom, which is the main therapy for victims of snakebite. Two basic myotoxins named MjTX-I and MjTX-II were isolated from Bothrops moojeni venom. Both myotoxins have a Lys-49 phospholipase A2 structure devoid of enzymatic activity, but are highly myonecrotic and edema-inducing. In this study, we analyzed the effect of a low-level laser (LLL) at 685 nm, an energy density of 2.2 J cm(-2), and the irradiation time of 15 s, and a light emitting diode (LED) at 635 or 945 nm at energy densities of 4 and 3.8 J cm(-2), and irradiation times of 41 and 38 s, respectively, applied 30 min and 3 h after edema formation in mice caused by MjTX-I or MjTX-II. MjTX-I or MjTX-II caused a significant edema formation in envenomed paws. LLL and LED irradiation significantly reduced the edema formation by both myotoxins from 1 up to 6 hours after the injection. Both LLL and LEDs were similar in reducing the edema formation induced by myotoxins. The combined photobiostimulation with antivenom had the same effect in reducing edema as treatment with the LLL or LEDs alone. In conclusion, the results of this study indicate that photobiostimulation could be used in association with antivenom therapy for treatment of local effects of Bothrops species venom.

Low-level laser therapy (LLLT) reduces the COX-2 mRNA expression in both subplantar and total brain tissues in the model of peripheral inflammation induced by administration of carrageenan.

In the classical model of edema formation and hyperalgesia induced by carrageenan administration in rat paw, the increase in prostaglandin E2 (PGE2) production in the central nervous system (CNS) contributes to the severity of the inflammatory and pain responses. Prostaglandins are generated by the cyclooxygenase (COX). There are two distinct COX isoforms, COX-1 and COX-2. In inflammatory tissues, COX-2 is greatly expressed producing proinflammatory prostaglandins (PGs). Low-level laser therapy (LLLT) has been used in the treatment of inflammatory pathologies, reducing both pain and acute inflammatory process. Herein we studied the effect of LLLT on both COX-2 and COX-1 messenger RNA (mRNA) expression in either subplantar or brain tissues taken from rats treated with carrageenan. The experiment was designed as follows: A1 (saline), A2 (carrageenan-0.5 mg/paw), A3 (carrageenan-0.5 mg/paw + LLLT), A4 (carrageenan-1.0 mg/paw), and A5 (carrageenan-1.0 mg/paw + LLLT). Animals from the A3 and A5 groups were irradiated at 1 h after carrageenan administration, using a diode laser with an output power of 30 mW and a wavelength of 660 nm. The laser beam covered an area of 0.785 cm(2), resulting in an energy dosage of 7.5 J/cm(2). Both COX-2 and COX-1 mRNAs were measured by RT-PCR. Six hours after carrageenan administration, COX-2 mRNA expression was significantly increased both in the subplantar (2.2-4.1-fold) and total brain (8.65-13.79-fold) tissues. COX-1 mRNA expression was not changed. LLLT (7.5 J/cm(2)) reduced significantly the COX-2 mRNA expression both in the subplantar (~2.5-fold) and brain (4.84-9.67-fold) tissues. The results show that LLLT is able to reduce COX-2 mRNA expression. It is possible that the mechanism of LLLT decreasing hyperalgesia is also related to its effect in reducing the COX-2 expression in the CNS.

Dosimetric effects of swelling or shrinking tissue during helical tomotherapy breast irradiation. A phantom study.

During radiation therapy of the female breast, the actual target volume compared to the planning target volume may change due to swelling or shrinking of the tissue. Under- or overdosage is to be expected, especially when performing IMRT or tomotherapy techniques. The objective of this study is to develop a model-based quantification of these dose effects, with a particular focus on the changes in the surface dose. A cylindrical phantom was used as an artificial surrogate of the human torso. By adding and removing Superflab layers of various thicknesses, both radial breast swelling and shrinking could be simulated. The effects on dose distribution were evaluated using film dosimetry. The results were compared to dose calculations. To estimate the true surface doses, we subtracted the influence of the film material on air measurements. During a swelling of 5, 10, and 15 mm, the planning target volume was consistently underdosed by 2%, 5%, and 7% of the prescribed dose, respectively. Swelling led to reduced dose values of up to 72%, 55%, and 50% at the outer edge of the actual target volume. The measured surface dose decreased successively from 31% to 23%. During shrinking, the dose in the planning target volume increased successively from 100% to 106%. The measured surface doses increased from 29% to 36%. The calculated dose values agreed with the measured values within error limits. During radiotherapy of the female breast, new planning appears to be essential for radial tissue swelling of 5 mm or more because of severe underdosing. Shrinking leads to moderate overdosing and an increased surface dose. In addition, caution is advised when removing bolus material with respect to the planned situation.

Effects of a low-level semiconductor gallium arsenide laser on local pathological alterations induced by Bothrops moojeni snake venom.

Antivenom therapy has been ineffective in neutralizing the tissue damage caused by snakebites. Among therapeutic strategies to minimize effects after envenoming, it was hypothesized that a low level laser would reduce complications and reduce the severity of local snake venom effects. In the current study, the effect of a low-level semiconductor gallium arsenide (GaAs) laser on the local pathological alterations induced by B. moojeni snake venom was investigated. The experimental groups consisted of five male mice, each administered either B. moojeni venom (VB), B. moojeni venom + antivenom (VAV), B. moojeni venom + laser (VL), B. moojeni venom + antivenom + laser (VAVL), or sterile saline solution (SSS) alone. Paw oedema was induced by intradermal administration of 0.05 mg kg(-1) of B. moojeni venom and was expressed in mm of directly induced oedema. Mice received by subcutaneous route 0.20 mg kg(-1) of venom for evaluating nociceptive activity and the time (in seconds) spent in licking and biting the injected paw was taken as an indicator of pain response. Inflammatory infiltration was determined by counting the number of leukocytes present in the gastrocnemius muscle after venom injection (0.10 mg kg(-1)). For histological examination of myonecrosis, venom (0.10 mg kg(-1)) was administered intramuscularly. The site of venom injection was irradiated by the GaAs laser and some animals received antivenom intraperitoneally. The results indicated that GaAs laser irradiation can help in reducing some local effects produced by the B. moojeni venom in mice, stimulating phagocytosis, proliferation of myoblasts and the regeneration of muscle fibers.

Prevention and treatment of mice paw edema by near-infrared low-level laser therapy on lymph nodes.

Low-level laser therapy (LLLT) has been demonstrated to modulate inflammatory processes and immunological responses. The aim of this work was to investigate the hypothesis that near infrared LLLT (830 nm) over lymph nodes may reduce paw edema and contribute to the modulation of inflammation. The edema was induced by carrageenan inoculation (CGN) into the plantar surface of 100 male mice left hind paw. Animals were divided into five groups: CGN (control), no treatment; Diclo, sodium diclofenac; Paw, LLLT on the paw; Ly, LLLT on the inguinal lymph nodes; and Paw+Ly, LLLT in both paw and lymph nodes, and subdivided according to moment of irradiation: A-1 h and 2 h before CGN, B-1 h and immediately before CGN, C-1 and 2 h after CGN, and D-3.5 and 4.5 h after CGN. The parameters used were: energy=1 J, fluence=35 J/cm(2), power=100 mW during 10 s. Paw volume was measured before and 1 to 6 h after CGN, and myeloperoxidase (MPO) activity was analyzed. Edema prevention was obtained by the irradiation of Paw+Ly at moment A and at Ly at moment B, inhibition of edema formation was achieved by either Paw or Ly at moment C, and edema treatment was obtained by Paw or Ly at moment D (p<0.05). MPO activity was significantly reduced on Paw at moment A, Paw and Ly on C, and in all irradiated groups on B and D. Our results suggest that LLLT was able to produce both anti-inflammatory and pro-inflammatory effects depending on to the site and moment of irradiation.

Edema-induced changes in tumor cell surviving fraction and tumor control probability in 131Cs permanent prostate brachytherapy implant patients.

The study is designed to investigate the effect of edema on the delivered dose, tumor cell surviving fraction (SF), and tumor control probability (TCP) in the patients of prostate cancer who underwent (131)Cs permanent seed implantation. The dose reduction, the SF, and the TCP for edematous prostate implants were calculated for 31 patients who underwent real-time (131)Cs permanent seed implantation for edema half-lives (EHL), ranging from 4 days to 34 days and for edema magnitudes (M0) varying from 5% to 60% of the actual prostate volume. A dose reduction in (131)Cs implants varied from 1.1% (for EHL = 4 days and M(0) = 5%) to 32.3% (for EHL = 34 days and M(0) = 60%). These are higher than the dose reduction in 125I implants, which vary from 0.3% (for EHL = 4 days and M(0) = 5%) to 17.5% (for EHL = 34 days and M(0) = 60%). As EHL increased from 4 days to 34 days and edema magnitude increased from 5% to 60%, the natural logarithmic value of SF increased by 4.57 and the TCP decreased by 0.80. Edema induced increase in the SF and decrease in the TCP in (131)Cs seed implants, is significantly more pronounced in a combination of higher edema magnitude and larger edema half-lives than for less edema magnitude and lower edema half-lives, as compared for M(0) = 60% and EHL = 34, and M(0) = 5% and EHL = 4 days.

Efficacy of low-level laser therapy in the management of pain, facial swelling, and postoperative trismus after a lower third molar extraction. A preliminary study.

Pain, swelling, and trismus are the most common complications after surgical removal of impacted lower third molars. The aim of this study was to evaluate the analgesic and anti-inflammatory effects of a low-level laser therapy (Laser Smile™, Biolase®, San Clemente, USA) applied to the wound appeared after the surgical removal of impacted lower third molars. A prospective, randomized, and double-blind study was undertaken in 20 healthy patients with two symmetrically impacted lower third molars. The application of a low-level laser was made randomly on one of the two sides after surgery. The experimental side received 5 J/cm(2) of energy density, a wavelength of 810 nm, and an output power of 0.5 W. On the control side, a handpiece was applied intraorally, but the laser was not activated. Evaluations of postoperative pain, trismus, and swelling were made. The sample consisted of 11 women and nine men, and mean age was 23.35 years (18-37). The pain level in the first hours after surgery was lower in the experimental side than in the placebo side, although without statistically significant differences (p = 0.258). Swelling and trismus at the 2nd and 7th postoperative days were slightly higher in the control side, although not statistically significant differences were detected (p > 0.05). The application of a low-level laser with the parameters used in this study did not show beneficial affects in reducing pain, swelling, and trismus after removal of impacted lower third molars.

Photobiomodulation therapy on local effects induced by juvenile and adult venoms of Bothrops alternatus.

Bothrops snake envenomation is characterized by severe local manifestations such as pain, edema, inflammation, hemorrhage, and myonecrosis. Furthermore, it is described that venom from juvenile and adult snakes may have differences in their composition that can lead to differences in the evolution of the clinical manifestation of the victim. Photobiomodulation (PBM) has been shown to be an effective adjuvant therapy to serum therapy to reduce the local effects induced by bothropic snake venom. This study evaluated the effect of PBM on the local reaction, after Bothrops alternatus snake venom (BaV) injection, in its juvenile (BaJV) and adult (BaAV) stages. Balb/C mice were injected with the juvenile or adult venoms of BaV or saline solution (control group). PBM at a wavelength of 660 nm, 100 mW, 0.33 W/cm2, 40 s, and a 0.028 cm2 beam was applied transcutaneous to a single point with a radiant exposure of 4 J/cm2, 30 min after venom injection. Edema, inflammatory infiltrate, hyperalgesia, and myonecrosis were analyzed. Both venoms induced significant edema and myonecrosis in the gastrocnemius muscle. Hyperalgesia in the mice paw and a prominent leukocyte infiltrate into the peritoneum were also observed. PBM significantly reduced all evaluated parameters. In conclusion, PBM treatment was effective in reducing the local effects induced by B. alternatus venom at different stages of snake development and could be a useful tool as an adjuvant treatment for bothropic envenomation.

Pulsed radio frequency energy (PRFE) use in human medical applications.

A number of electromagnetic field-based technologies are available for therapeutic medical applications. These therapies can be broken down into different categories based on technical parameters employed and type of clinical application. Pulsed radio frequency energy (PRFE) therapy is a non invasive, electromagnetic field-based therapeutic that is based on delivery of pulsed, shortwave radio frequency energy in the 13-27.12 MHz carrier frequency range, and designed for local application to a target tissue without the intended generation of deep heat. It has been studied for use in a number of clinical applications, including as a palliative treatment for both postoperative and non postoperative pain and edema, as well as in wound healing applications. This review provides an introduction to the therapy, a summary of clinical efficacy studies using the therapy in specific applications, and an overview of treatment-related safety.

Effects of photobiomodulation therapy on the local experimental envenoming by Bothrops leucurus snake.

Bothrops leucurus is the major causative agent of snakebites in Brazil's Northeast. The systemic effects of its venom are effectively neutralized by antivenom therapy, preventing bitten patients' death. However, antivenom fails in neutralizing local effects that include intense pain, edema, bleeding, and myonecrosis. Such effects can lead to irreversible sequels, representing a clinically relevant issue for which there is no current effective treatment. Herein, the effects of photobiomodulation therapy (PBMT) were tested in the local actions induced by B. leucurus venom (BLV) in mice (n = 123 animals in 20 experimental groups). A continuous emission AlGaAs semiconductor diode laser was used in two wavelengths (660 or 780 nm). Mechanical nociceptive thresholds were assessed with the electronic von Frey apparatus. Local edema was determined by measuring the increase in paw thickness. Hemorrhage was quantified by digital measurement of the bleeding area. Myotoxicity was evaluated by serum creatine kinase (CK) activity and histopathological analysis. PBMT promoted anti-hypernociception in BLV-injected mice; irradiation with the 660 nm laser resulted in faster effect onset than the 780 nm laser. Both laser protocols reduced paw edema formation, whether irradiation was performed immediately or half an hour after venom injection. BLV-induced hemorrhage was not altered by PBMT. Laser irradiation delayed, but did not prevent myotoxicity caused by BLV, as shown by a late increase in CK activity and histopathological alterations. PBMT was effective in the control of some of the major local effects of BLV refractory to antivenom. It is a potential complementary therapy that could be used in bothropic envenoming, minimizing the morbidity of these snakebite accidents.

Absence of prostate oedema obviates the need for delay between fiducial marker insertion and radiotherapy simulation.

INTRODUCTION: Fiducial markers (FMs) are commonly inserted into the prostate for image guided radiation therapy. This study aimed to quantify prostate oedema immediately following FM insertion compared to prostate volumes measured a week later, at the time of simulation for radiation therapy. METHODS: Thirty patients underwent a verification computed tomography (VCT) scan in treatment position immediately after the fiducial insertion and their planning computed tomography scan (PCT) one week after. Patient data sets were retrospectively evaluated, comparing prostate volumes and planning target volumes (PTV). Volumes were delineated by a single radiation oncologist, blinded to whether the scan was VCT or PCT. Distances between the FMs were measured on both scans. Descriptive statistics described the data, DICE similarity co-efficient (DSC) calculated, and paired t-tests were used to compare paired data. RESULTS: The median prostate volume was 35.09 cc and 36.31 cc for VCT and PCT data sets, respectively, and median PTV was 118.56 cc and 127.04 cc for VCT and PCT, respectively. There was no significant difference in prostate volumes (P = 0.3037) or PTV (P = 0.1279), with a DSC of 0.87 (range 0.76-0.91) and 0.91 (range 0.85 to 0.95), respectively. Similarly, there was no significant difference in distance between fiducial markers (P > 0.05). CONCLUSION: This study demonstrates no statistically significant difference in prostate or PTV volumes (P > 0.05) between the CT acquired at fiducial marker insertion compared with the CT acquired a week later. Therefore, oedema is not significant enough to justify a delay between FM insertion and simulation.

Photobiomodulation as oedema adjuvant in post-orthognathic surgery patients: A randomized clinical trial.

OBJECTIVE: Photobiomodulation therapy (PBMT) has been used in multiple applications in general medicine as powerful anti-inflammatory, analgesic and reducing oedema in different parts of the body. The aim of this study is to compare the effect on post-surgical oedema after mandibular orthognathic surgery, between two different laser power densities and oral medication with non-steroidal anti-inflammatory. MATERIALS AND METHODS: In a randomized clinical trial, on 60 patients who were subject to mandibular orthognathic surgery were divided into three groups. All groups received sodium naproxen 250mg every 8hours for 6days. Two groups were irradiated with two different laser application protocols and the other was a control group. In G1 group the irradiation parameters three times per week for two weeks were: 940nm, in continuous mode, 2.5W, 120s, 85.71J/cm2, 0.89W/cm2, over the right and left side with a distance from the skin surface of 1mm with the whitening handpiece (spot size of 2.8cm2). In G2, the irradiation parameters three times a week for two weeks were: 940nm, in continuous mode, 4.1W, 120s, 68.33J/cm2, 0.58W/cm2 over the right and left side with a distance from the skin surface of 15mm, with the deep tissue handpiece (spot size of 7.1cm2). In all the groups, millimetric facial measurements were taken from tragus to lateral commissure, and from lateral commissure to gonion in both sides. RESULTS: All differences between T1 and T6 were significant for the three groups, (paired T, P<0.05). The differences between the groups were generally not significant (P>0.05) except for commissure - right and left gonion when compared G1 vs CG (P<0.05) and G2 vs CG (P<0.05). Initial changes (T1-T2) between groups were significantly different except for the measurement from commissure to right tragus G1 vs CG (P=0.411) and from commissure to left tragus G2 vs CG (P=0.94). The faster resolution of the oedema occurred in G2 group. PTBM with an energy density of 68.33J/cm2 was the most effective adjuvant to oral medication with non-steroidal anti-inflammatory, to decrease post-surgical oedema after mandibular orthognathic surgery.

Photobiomodulation therapy reduces acute pain and inflammation in mice.

Photobiomodulation (PBM) is a therapy suggested for the treatment of pain and inflammation. Different mechanisms have been proposed to explain the analgesic and inflammatory effects of photobiomodulation, but there are still gaps on the mechanisms underlying. The objective was to investigate the analgesic and anti-inflammatory effect of red LED, as well as to investigate the possible mechanism of action in acute nociception models. Radiation was applied with red LED (660 nm, 215 mW, 84.64 mW/cm2, 2.531 J/cm2 (30s); 5.07 J/cm2 (60s) 7.61 J/cm2 (90s) and 10.15 J/cm2 (120 s)). The red LED applied 60 s before the experiments, promoted reduction of the nociceptive neurogenic (1st phase) and inflammatory pain (2nd phase) induced by intraplantar (i.pl.) injection of formalin. This effect duration in the second phase was 180 min after pretreatment of the LED. Red LED also reduced nociception induced by intraperitoneal injection of acetic acid. Furthermore, red LED prevented nociception induced by i.pl. injection of cinnamaldehyde, capsaicin, menthol and acidified saline. It was demonstrate the involvement of glutamatergic system with the reduction the nociception induced by glutamate. The red LED was able to prevent nociception induced by intracellular signaling cascades activators, phorbol 12-myristate 13-acetate (PMA), bradykinin, forskolin and prostaglandin. In addition, red LED, respectively, from 30 to 90s demonstrated an antiedematogenic effect on ear edema and reduction the migration of inflammatory cells induced by single application of croton oil. Thus, the new findings in this study support some underlying mechanism by which red LED phototherapy reduces acute pain. However, need further clarification regarding analgesic and anti-inflammatory effect of the photobiomodulation in preclinical studies.

Low level laser therapy modulates kinin receptors mRNA expression in the subplantar muscle of rat paw subjected to carrageenan-induced inflammation.

Low level laser therapy (LLLT) has been used clinically in order to treat inflammatory processes. In this work, we evaluated if LLLT alters kinin receptors mRNA expression in the carrageenan-induced rat paw edema. Experimental groups were designed as followed: A1 (Control-saline), A2 (Carrageenan-only), A3 (Carrageenan+laser 660 nm) and A4 (Carrageenan+laser 684 nm). Edema was measured by a plethysmometer. Subplantar tissue was collected for kinin receptors mRNA quantification by Real time-PCR. LLLT of both 660 and 684 nm wavelengths administrated 1 h after carrageenan injection was able to promote the reduction of edema produced by carrageenan. In the A2 group, B1 receptor expression presented a significantly increase when compared to control group. Kinin B1 receptor mRNA expression significantly decreased after LLLT's 660 or 684 nm wavelength. Kinin B2 receptor mRNA expression also diminished after both laser irradiations. Our results suggest that expression of both kinin receptors is modulated by LLLT, possibly contributing to its anti-inflammatory effect.

Anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation: frequency and power dependence.

Using a model of acute zymosan-induced footpad edema in NMRI mice, the frequency and power dependence of anti-inflammatory effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR) was found. Single whole-body exposure of animals to EHF EMR at the intensity of 0.1 mW/cm(2) for 20 min at 1 h after zymosan injection reduced both the footpad edema and local hyperthermia on average by 20% at the frequencies of 42.2, 51.8, and 65 GHz. Some other frequencies from the frequency range of 37.5-70 GHz were less effective or not effective at all. At fixed frequency of 42.2 GHz and intensity of 0.1 mW/cm(2), the effect had bell-shaped dependence on exposure duration with a maximum at 20-40 min. Reduction of intensity to 0.01 mW/cm(2) resulted in a change of the effect dependence on exposure duration to a linear one. Combined action of cyclooxygenase inhibitor sodium diclofenac and EHF EMR exposure caused a partial additive effect of decrease in footpad edema. Combined action of antihistamine clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti-inflammatory effect of EHF EMR. The results obtained suggest that arachidonic acid metabolites and histamine are involved in realization of anti-inflammatory effects of low-intensity EHF EMR.

Light emitting diode (LED) therapy reduces local pathological changes induced by Bothrops asper snake venom.

The therapeutic effect of the Light Emitting Diode (LED) treatment in two wavelengths (635 or 945 nm) was evaluated in the local pathological alterations induced by Bothrops asper snake venom. Mice received irradiation of infrared LED (120 mW, 945 nm) or red LED (110 mW, 635 nm) applied immediately, 1 and 2 h after venom injection. LED treatment reduced edema formation in the plantar region and gastrocnemius muscle and significantly reduced neutrophil migration and hyperalgesia after the venom injection. Also, both infrared LED and red LED treatment significantly reduced myonecrosis, as revealed by muscle CK and plasma CK levels. Histological analysis corroborated the reduction in the extent of venom-induced myonecrosis. In conclusion, our data demonstrates that PBM with LED light in both red and infrared wavelengths, when applied after envenomation in mice, reduces the extent of myotoxicity, edema, inflammatory infiltrate and hyperalgesia, suggesting that photobiomodulation is a potential therapeutic approach that should be further investigated for the treatment of local effects of Bothrops snakebite.