Participation of Potential Transient Receptors in the Antinociceptive Effect of Pharmacopuncture.

Background: Despite the widespread clinical use of acupuncture in painful situations, the use of this treatment should be further clarified. Nociception is mediated by the activation of nociceptors, such as transient receptor potentials (TRPs). The family of TRPs includes TRPV1, TRPM8, and TRPA1, which can be stimulated by substances such as capsaicin, menthol, and methyl salicylate, respectively. Objectives: This study aimed to investigate the role of TRPs in antinociception via the administration of agonists of these receptors in the Zusanli acupoint (ST36) in models of inflammatory, acute, and neuropathic pain. Methods: Male Wistar rats were used for this experiment. All rats received a subcutaneous injection of TRP agonists (capsaicin, menthol, or methyl salicylate) in ST36; saline was injected as control. Nociception was evaluated using the electronic mechanical threshold test and tail-flick test before the administration of complete Freund's adjunct or chronic constriction injury of the sciatic nerve and after the administration of TRP agonists. Results: Nociception was found to be attenuated after treatment with TRP agonists. The administration of different doses (0.03, 0.3, and 3.0 µg/20 µL) of capsaicin, menthol, and methyl salicylate in the different pain models (neuropathic, inflammatory, and nociceptive) induced antinociception in most of the evaluated time points. Conclusion: Based on the findings, we suggest that the activation of TRPV1, TRPM8, and TRPA1 receptors results in the antinociceptive effect of the stimulation of the ST36 acupoint. Thus, TRP receptors may present a new therapeutic opportunity for the control of inflammatory and neuropathic pain.

Intense Pulsed Light on skin rejuvenation: a systematic review.

Aged skin is characterized by appearance of wrinkles, vascular lesions, hyperpigmentation, lentignes, texture, rhytides, and pores. These changes occur under the influence of intrinsic and extrinsic factors, as hormone alterations and exposure to ultraviolet light (UV) irradiation, respectively. Skin changes associated with aging have been assuming an important role in nowadays and bring to affect the quality of life. Intense Pulsed Light (ILP) is a noncollimated, polychromatic, and noncoherent non-surgical cosmetic therapy to skin rejuvenation. This is the first systematic review evaluating ILP treatment on skin rejuvenation evaluated by digital photographs and self-reported treatment efficacy. A PRISMA compliant review includes a search of the databases Scopus and PubMed. Sixteen studies treating 637 participants (with Fitzpatrick skin types I to IV and age varying from 21 to 80 years) were included. Patients were treated a mean of 4.29 sessions (range 3-7). The most studies results showed the efficacy of IPL treatment in telangiectasia, wrinkles, pore, erythema, rhytids, texture, lentigines, hiperpigmentation, and photoaging score. Six studies showed IPL-positive effects in association with other treatment and seven studies showed superior effect of other treatment or association to IPL with other treatment related to IPL alone. Nine studies showed low methodological quality. In conclusion, ILP treatment is effective on skin rejuvenation. However, there is no consensus about the parameters and future studies are needed to sample size limitations, made RCTs with low risk of bias, and improve the methodological quality its. Trial registration: Prospero Systematic Review Registration ID: CRD42021237817.

Bone substitutes and photobiomodulation in bone regeneration: A systematic review in animal experimental studies.

In general, bone fractures are able of healing by itself. However, in critical situations such as large bone defects, poor blood supply or even infections, the biological capacity of repair can be impaired, resulting in a delay of the consolidation process or even in non-union fractures. Thus, technologies able of improving the process of bone regeneration are of high demand. In this context, ceramic biomaterials-based bone substitutes and photobiomodulation (PBM) have been emerging as promising alternatives. Thus, the present study performed a systematic review targeting to analyze studies in the literature which investigated the effects of the association of ceramic based bone substitutes and PBM in the process of bone healing using animal models of bone defects. The search was conducted from March and April of 2019 in PubMed, Web of Science and Scopus databases. After the eligibility analyses, 16 studies were included in this review. The results showed that the most common material used was hydroxyapatite (HA) followed by Biosilicate associated with infrared PBM. Furthermore, 75% of the studies demonstrated positive effects to stimulate bone regeneration from association of ceramic biomaterials and PBM. All studies used low-level laser therapy (LLLT) device and the most studies used LLLT infrared. The evidence synthesis was moderate for all experimental studies for the variable histological analysis demonstrating the efficacy of techniques on the process of bone repair stimulation. In conclusion, this review demonstrates that the association of ceramic biomaterials and PBM presented positive effects for bone repair in experimental models of bone defects.

Marine spongin incorporation into Biosilicate® for tissue engineering applications: An in vivo study.

Biomaterials and bone grafts, with the ability of stimulating tissue growth and bone consolidation, have been emerging as very promising strategies to treat bone fractures. Despite its well-known positive effects of biosilicate (BS) on osteogenesis, its use as bone grafts in critical situations such as bone defects of high dimensions or in non-consolidated fractures may not be sufficient to stimulate tissue repair. Consequently, several approaches have been explored to improve the bioactivity of BS. A promising strategy to reach this aim is the inclusion of an organic part, such as collagen, in order to mimic bone structure. Thus, the present study investigated the biological effects of marine spongin (SPG)-enriched BS composites on the process of healing, using a critical experimental model of cranial bone defect in rats. Histopathological and immunohistochemistry analyzes were performed after two and six weeks of implantation to investigate the effects of the material on bone repair (supplemental material-graphical abstract). Histological analysis demonstrated that for both BS and BS/SPG, similar findings were observed, with signs of material degradation, the presence of granulation tissue along the defect area and newly formed bone into the area of the defect. Additionally, histomorphometry showed that the control group presented higher values for Ob.S/BS (%) and for N.Ob/T.Ar (mm2) (six weeks post-surgery) compared to BS/SPG and higher values of N.Ob/T.Ar (mm2) compared to BS (two weeks post-surgery). Moreover, BS showed higher values for OV/TV (%) compared to BS/SPG (six weeks post-surgery). Also, VEGF immunohistochemistry was increased for BS (two weeks post-surgery) and for BS/SPG (six weeks) compared to CG. TGFb immunostaining was higher for BS compared to CG. The results of this study demonstrated that the BS and BS/SPG scaffolds were biocompatible and able to support bone formation in a critical bone defect in rats. Moreover, an increased VEGF immunostaining was observed in BS/SPG.

Level of pain, muscle strength and posture: effects of PBM on an exercise program in women with knee osteoarthritis - a randomized controlled trial.

To evaluate the effectiveness of an exercise program associated to photobiomodulation (PBM) on pain, postural changes, functionally, and muscular strength in women, one of the risk factors, with knee osteoarthritis (OA). A randomized controlled trial, with a blinded assessor and intention-to-treat analysis and placebo control. Sixty-two participants with knee OA (with confirmed radiological diagnosis) were evaluated for this study. However, 34 were considered eligible and were randomized into two groups: EPPG - exercise and PBM placebo group (n = 17) and EPAG - exercise and PBM active group (n = 16), but one participant was excluded of EPAG. The exercise program and PBM (808 nm, 100 mW/point, 4 J/point, 56 J total, 91 J/cm2) were realized twice a week, during 8 weeks. West Ontario and the McMaster University Osteoarthritis Index (WOMAC) and Lequesne questionnaires, 1-repetition maximum test (1-RM) and posture evaluation software (SAPO) were used to analyze the effects of the therapies. In intragroup analysis, a significant improvement in pain WOMAC (p < 0.001), stiffness (p < 0.001), function (p < 0.001), Lequesne (p < 0.001), and 1-RM (all muscle groups) (p < 0.001) were observed. In this study, the exercise program improved pain, function, and muscle strength of all the participants. However, PBM, in the parameters used, did not optimize the effects of the exercise program in women with knee OA.

Effect of photobiomodulation associated with cell therapy in the process of cutaneous regeneration in third degree burns in rats.

Due to the complexity involved in the healing process of full thickness burns, the literature looks for alternatives to optimize tissue reconstruction. The objective of this study was to explore the action of photobiomodulation therapy associated with MSCs in the healing process of third degree burns. A total of 96 male Wistar rats were used, distributed in four groups with 24 animals each: Control Group, Laser Group, Cell Therapy Group, and Laser Group and Cell Therapy. The burn was performed with aluminum plate (150 °C). We performed analysis of wound contraction, histology, immunohistochemistry, birefringence analysis, and immunoenzymatic assay to evaluate tissue quality. Our results demonstrate that the association of the techniques is able to accelerate the repair process, modulating the inflammatory process, presenting a cutaneous tissue with better quality. Thus, we conclude that the use of photobiomodulation therapy associated with cell therapy is a promising treatment in the repair of total thickness burns.

The photobiomodulation (658, 830 and 904nm) on wound healing in histomorphometric analysis / A fotobiomodulação (658, 830 e 904nm) na cicatrização de feridas na análise histomorfométrica / La fotobiomodulación (658, 830 y 904nm) en la cicatrización de heridas en el análisis histomorfométrico

Abstract Introduction: Photobiomodulation (PBM) assists in the processes of angiogenesis and cellular mitosis after skin lesion, contributing to tissue repair. Objective: to investigate the effects of photobiomodulation (during the proliferative phase) of 658 nm, 830 nm and 904 nm in the repair of skin lesions in an animal model. Method: 658 nm (G658), 830 nm (G830), 904 nm (G904) PBM, and control group (CG) integrated the research. We submitted the animals to an excisional wound and treatment at different wavelengths for 14 days. On the seventh and 14-1485004059th postoperative days, we calculated the area and percentage of lesion contraction. The animals were sacrificed on the 14-1485004056th postoperative day and cutaneous section of the injured region was collected for histomorphometric evaluation of the cellularity, neovascularization, thickness of the epidermis and volume density of collagen fibers colored with H&E and Picross Sirius respectively. For the statistical analysis, we applied the ANOVA test. Results: the G658 presented higher cellularity than GC (p = 0.03). The animals in the G658 group showed a significant increase in the neovascularization in relation to the CG (p = 0.01). Type III collagen significantly increased in G904 compared to G830 (p < 0.0001) and CG (p < 0.0001). The G658 had a significant increase in type III collagen fibers compared to G830 (p < 0.0001) and GC (p < 0.0001). We found no significant difference in the thickness of the epidermis, wound area, and in the percentage wound of contraction between the analyzed groups. Conclusion: PBM was effective to stimulate the tissue repair process, with better results for the 658 nm wavelength.

Resumo Introdução: A Fotobiomodulação (FBM) auxilia nos processos de angiogênese e mitose celular após lesão cutânea, contribuindo para reparo do tecido. Objetivo: investigar os efeitos da fotobiomodulação (durante a fase proliferativa) com comprimento de onda de 658 nm, 830 nm e 904 nm no reparo de lesões cutâneas em modelo animal. Método: FBM 658 nm (G658), 830 nm (G830), 904 nm (G904) e controle (GC) integraram a pesquisa. Os animais foram submetidos a uma ferida excisional e receberam tratamento em diferentes comprimentos de por 14 dias. No 7º e 14º dia pós-operatório, calculou-se a área e a porcentagem de contração da lesão. Os animais foram sacrificados no 14º dia pós-operatório e a secção cutânea da região lesada foi coletada para avaliação histomorfométrica da celularidade, neovascularização, espessura da epiderme e densidade volumétrica das fibras colágenas, corados com H&E e Picross Sirius respectivamente. Para a análise estatística, foi aplicado o teste ANOVA. Resultados: o G658 apresentou maior celularidade que GC (p = 0,03). Os animais do grupo G658 apresentaram aumento significativo da neovascularização em relação ao GC (p = 0,01). Houve aumento significativo do colágeno tipo III no G904 em relação ao G830 (p < 0,0001) e GC (p < 0,0001). O G658 teve um aumento significativo nas fibras colágenas tipo III em comparação ao G830 (p < 0,0001) e GC (p < 0,0001). Nenhuma diferença significativa foi encontrada na espessura da epiderme, área da ferida e na porcentagem de contração da ferida entre os grupos analisados. Conclusão: a PBM foi efetiva para estimular o processo de reparo tecidual, com melhores resultados para o comprimento de onda de 658 nm.

Resumen Introducción: La fotobiomodulación (FBM) auxilia en los procesos de angiogénesis y mitosa celular después de lesión cutánea, contribuyendo para la reparación. Objetivo: investigar los efectos de la fotobiomodulación (durante la fase proliferativa) con longitud de onda de 658 nm, 830 nm y 904 nm en la reparación de lesiones cutáneas en modelo animal. Método: grupos de FBM 658 nm (G658), 830 nm (G830), 904 nm (G904) y control (GC) integraron la investigación. Los animales fueron sometidos a una herida excisional y recibieron tratamiento 14 días. En el 7º y 14º día postoperatorio, se calculó el área y el porcentaje de contracción de la lesión. Los animales fueron sacrificados en el 14º día postoperatorio y la sección cutánea de la región lesada fue recolectada para evaluación histomorfométrica de la celularidad, neovascularización, espesor de la epidermis y densidad volumétrica de las fibras colágenas, colorados con H & E y Picross Sirius respectivamente. Para el análisis estadístico, se aplicó la prueba ANOVA. Resultados: G658 presentó mayor celularidad que GC (p = 0,03). G658 presentaron un aumento significativo de la neovascularización en relación al GC (p = 0,01). Se observó un aumento significativo del colágeno tipo III en el G904 con respecto al G830 (p < 0,0001) y GC (p < 0,0001). El G658 tuvo un aumento significativo en las fibras colágenas tipo III en comparación con el G830 (p < 0,0001) y GC (p < 0,0001). Ninguna diferencia significativa se encontró en el espesor de la epidermis, área de la herida entre los grupos. Conclusión: la PBM fue efectiva para estimular el proceso de reparación del tejido, con mejores resultados para grupo 658 nm.

Photobiomodulation effect on the proliferation of adipose tissue mesenchymal stem cells.

The use of mesenchymal stem cells (MSCs) in tissue engineering has been extensively investigated. The greater the proliferation of this cellular group, the greater the regenerative and healing capacity of the tissue to which they belong. In this context, photobiomodulation (PBM) is an efficient technique in proliferation of distinct cell types. However, its parameters and mode of action are still unclear and require further investigation. This study aimed to evaluate the PBM action with different energies in MSCs of adipose tissue (hASCs). We used hASCs, seeded in 24-well plates, with 3 × 104 cells per well, in culture media. We used a total of four experimental groups, one with hASCs and simulated PBM and three other groups, which received PBM irradiation at 24, 48, and 72 h, with a 660-nm laser and power of 40 mW and energy of 0.56, 1.96, and 5.04 J. We performed analyses of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidefor) and trypan blue to evaluate cell proliferation and viability, 1 h after PBM irradiation. Software Graph PadPrism 7.0 was used. Intergroup comparisons were performed with ANOVA two-way and we used the Tukey post hoc test. Mitochondrial activity evaluated by MTT revealed the statistical difference in the first 24 h for group with more high energy when compared to control group; and in the 72 h for two irradiated groups when compared to the control group. The trypan blue test showed significant differences at the end of the experiment for two irradiated groups LG1 (4.52 × 104 ± 0.2) and LG2 (4.85 × 104 ± 0.8), when compared to the control group (1.87 × 104 ± 0.7). Both tests failed to be statistically different at the end of the experiment for groups LG1 and LG2 and observed a reduction in cellular mitochondrial growth and activity for group LG3. We conclude that PBM with energy close to 0.56 and 1.96 J promote proliferation of hASCs, and higher energy, such as 5.04 J, can be harmful.

Opioidergic effects of transcutaneous electrical nerve stimulation on pain and inflammatory edema in a rat model of ankle sprain / Efeitos de opioidérgico da estimulação elétrica nervosa transcutânea sobre a dor e edema inflamatório em um modelo de entorse de tornozelo em ratos / Efectos opioidergicos de la estimulación nerviosa eléctrica transcutánea sobre el dolor y el edema inflamatorio en un modelo de rata con esguince de tobillo

ABSTRACT Although transcutaneous electrical nerve stimulation (TENS) has been proposed to modulate pain and the mechanisms underlying analgesia remain poorly understood, evidence of anti-inflammatory effect is more limited. The purpose of this study was to examine the opioidergic mechanisms of TENS effects in two different frequencies on pain and inflammatory edema in the ankle sprain model in rats. Threshold to mechanical stimulation was utilized to examine the changes produced by intraperitoneal injection of non-selective opioid antagonist naloxone on the antihyperalgesic effect induced by a 20-min period of 2Hz or 100Hz TENS in the ankle sprain model, produced by manually overextending the lateral ligaments. Ankle sprain induced a long-lasting reduction in paw withdrawn latency (PWL) after 30 minutes for up to 24 hours in sham TENS (SH-TENS) treated rats. The reduced PWL after the induction of ankle sprain was restored partially at 0,1,2,3 and 6, but not 24 hours, after the termination of 2 Hz-TENS (LF-TENS). In 100Hz (HF-TENS) the reduction in PWL was shorter than LF-TENS and both LF and HF effects were fully blocked in naloxone-treated rats. LF- and HF-TENS treated rats did not reach the elevation of edema and presented a progressive edema reduction for over 24 hours when compared to SH-TENS group. Both effects were reduced by naloxone. TENS-induced antihyperalgesic and anti-edematous effects observed in ankle sprain model were mediated by the endogenous opioid system.

RESUMO Embora estimulação elétrica nervosa transcutânea (TENS) tem sido proposta para modular a dor e os mecanismos subjacentes a analgesia permanecem mal compreendidos, evidências do efeito anti-inflamatório são mais limitadas. O objetivo deste estudo foi examinar os mecanismos opioidérgicos de efeitos de TENS em duas frequências diferentes sobre dor e edema inflamatório no modelo de entorse de tornozelo em ratos. Limiar de estimulação mecânica foi utilizado para examinar as alterações produzidas pela injeção intraperitoneal de naloxona, um antagonista opioide não-seletivo, sobre o efeito anti-hiperalgésico induzido por um período de 20 min de 2Hz ou 100Hz de TENS no modelo de entorse de tornozelo, produzido ultrapassando manualmente os ligamentos laterais. Entorse de tornozelo induziu uma redução duradoura na latência de retirada da pata (PWL) depois de 30 minutos até 24 horas em ratos tratados para TENS "simulada" (SH-TENS). A PWL reduzida após a indução de entorse de tornozelo foi restaurada parcialmente em 0,1,2,3 e 6, mas não em 24 horas, após o término do 2 Hz-TENS (LF-TENS). Em 100Hz (HF-TENS) a redução de PWL foi menor do que LF-TENS e tanto os efeitos HF e LF foram totalmente bloqueados em ratos tratados com naloxona. Ratos tratados com LF- e HF-TENS não alcançou a elevação do edema e apresentaram uma redução progressiva do edema por mais de 24 horas, quando comparado ao grupo SH-TENS. Ambos os efeitos foram reduzidos pela naloxona. Efeitos anti-hiperalgésicos induzidos por TENS e efeitos antiedematosos observados no modelo de entorse de tornozelo foram mediados pelo sistema de opioides endógenos.

RESUMEN Aunque la estimulación nerviosa eléctrica transcutánea (TENS) ha sido propuesta para modular el dolor y los mecanismos subyacentes a la analgesia sigue siendo mal entendida, la evidencia del efecto antiinflamatorio es limitada. El propósito de este estudio fue examinar los mecanismos opioidérgicos de los efectos de la TENS en dos frecuencias diferentes sobre el dolor y el edema inflamatorio en un modelo de ratas con esguince de tobillo. Se utilizó el umbral a la estimulación mecánica para examinar los cambios producidos por inyección intraperitoneal del antagonista opiáceo no selectivo naloxona sobre el efecto antihiperalgésico inducido por un período de 20 minutos de 2Hz o 100Hz TENS en el modelo con esguince de tobillo, producido por sobrecarga manual de los ligamentos laterales. El esguince de tobillo indujo una reducción de larga duración en latencia de la pata retraída (PWL) después de 30 minutos por hasta 24 horas en simulación de la TENS (SH-TENS) para las ratas tratadas. El PWL reducido después de la inducción del esguince de tobillo fue restaurado parcialmente en 0,1,2,3 y 6, pero no por 24 horas, después de la terminación de 2 Hz-TENS (LF-TENS). La reducción en PWL fue menor que LF-TENS en 100Hz (HF-TENS) y tanto los efectos de LF como de HF fueron completamente bloqueados en ratas tratadas con naloxona. Las ratas tratadas con LF- y HF-TENS no alcanzaron la elevación del edema y presentaron una reducción progresiva del edema durante más de 24 horas en comparación con el grupo SH-TENS. Ambos efectos fueron reducidos por la naloxona. Efectos antihiperalgésicos y antiedematosos TENS-inducidos observados en el modelo con esguince de tobillo fueron mediados por el sistema opioide endógeno.