Central involvement of 5-HT1A receptors in antinociception induced by photobiomodulation in animal model of neuropathic pain.

This study aimed to investigate the central involvement of 5-HT1A receptors in the nociceptive behavior of mice submitted to the chronic constriction injury (CCI) of sciatic nerve and the subsequent application of photobiomodulation (PBM). Male mice (Swiss-albino) were submitted to CCI and subsequently received an infusion of WAY100635 (5-HT1A receptor antagonist) or intracerebroventricular saline (ICV), followed by infrared laser irradiation (808 nm), in continuous mode, with the power of 100 mW and a dose of 0 J/cm2 (control group) or 50 J/cm2. The thermal hyperalgesia was evaluated by hot plate test, while mechanical allodynia was evaluated by von Frey filaments. After CCI, animals showed a reduction in the nociceptive threshold (p<0.001) when compared to the sham group. In von Frey test, the CCI + saline + PBM 50 J/cm2 group showed an increase in nociceptive threshold (p<0.001) in all measurement moments in comparison with groups CCI + SALINE + PBM 0 J/cm2, CCI + WAY100635 + PBM 50 J/cm2, and CCI + WAY100635 + PBM 0 J/cm2. Similarly, in hot plate test, CCI + SALINE + PBM 50 J/cm2 group showed an increase in nociceptive threshold after application of PBM at 120 and 180 min. Because of the results found, it can be suggested the involvement of 5-HT1A receptors in the central nervous system, since WAY100635 was able to reverse the antinociceptive effect provided by PBM in animals submitted to CCI.

Differential involvement of central and peripheral α2 adrenoreceptors in the antinociception induced by aerobic and resistance exercise.

BACKGROUND: Several studies have demonstrated antinociception induced by exercise; however, the specific mechanisms for this effect are not well understood. Thus, we investigated the involvement of α2-adrenergic receptors (α2-ARs) in the antinociceptive effect produced by exercise in rats and mice. METHODS: Male Wistar rats performed acute aerobic (AA) and acute resistance exercise protocols, and male α2A/α2C-ARs knockout mice and their wild-type mice were also submitted to AA. RESULTS: After the exercise protocols, the nociceptive threshold of rats and wild type was increased, (except in knockout mice). This effect was reversed by yohimbine, a nonselective α2-ARs antagonist (4 mg/kg, subcutaneously [s.c.]); rauwolscine, a selective α2C-ARs antagonist (4 mg/kg, s.c.); BRL 44408, a selective α2A-ARs antagonist (4 mg/kg, s.c.) and guanethidine, a selective inhibitor of transmission in adrenergic nerves (30 mg/kg, intraperitoneal). Furthermore, when given intrathecally or intracerebroventricularly, yohimbine did not alter antinociception induced by exercise protocols. In addition, α2-ARs expression in rat brains did not change after AA and acute resistance exercise. CONCLUSION: These results suggest a peripheral involvement of α2-ARs in the antinociception induced by aerobic and resistance exercise.

Effects of nanocapsules of poly-ε-caprolactone containing artemisinin on zebrafish early-life stages and adults.

Artemisinin extracted from Artemisia annua L. plants has a range of properties that qualifies it to treat several diseases, such as malaria and cancer. However, it has short half-life, which requires making continuous use of it, which has motivated the association of artemisinin (ART) with polymeric nanoparticles to increase its therapeutic efficiency. However, the ecotoxicological safety of this association has been questioned, given the scarcity of studies in this area. Thus, in this work the toxicity of Poly (ε-Caprolactone) nanocapsules added with ART (ART-NANO) in zebrafish (Danio rerio), embryos and adults was studied. Different endpoints were analyzed in organisms exposed to ART-NANO, including those predictive of embryotoxicity and histopatoxicity. Embryotoxicity was analyzed based on Organization for Economic Co-operation and Development (OECD) test guideline (236) for fish embryo acute toxicity applied to zebrafish (Danio rerio) at 96 hpf under five nominal logarithmic concentrations (0.125 to 2.0 mg/ L). Our results demonstrate, mainly, that fertilized eggs presented increased coagulation, lack of heart rate, vitelline sac displacement and lack of somite formation. On the other hand, adult individuals (exposed to the same concentrations and evaluated after 24 and 96 h of exposure) have shown increased pericarditis. Therefore, the treatment based on ART, poly (ε-caprolactone) nanocapsules and on their combination at different concentrations have shown toxic effects on zebrafish embryos and adult individuals.

Endocannabinoid mechanism for orofacial antinociception induced by electroacupuncture in acupoint St36 in rats.

INTRODUCTION: This study was conducted with the aim of evaluating whether electroacupuncture (EA) at acupoint St36 could produce antinociception through the activation of an endocannabinoid mechanism. METHODS: Male Wistar rats were divided into experimental groups. Heat was applied to the faces of rats, and the latency to withdraw the face was measured. Furthermore, the influence of electrical stimulation (100HzP) of acupoint St36, at a 0.5mA intensity, was investigated in the facial withdrawal threshold. RESULTS: The EA produced antinociception, which lasted for 180min. This effect was antagonized by the pre-injection of AM 251, a CB1 cannabinoid receptor antagonist, but not by AM 630, a CB2 cannabinoid receptor antagonist. Additionally, pretreatment with an endocannabinoid metabolizing enzyme inhibitor (MAFP) and an anandamide reuptake inhibitor (VDM11) prolonged and intensified the antinociceptive effect produced by EA. CONCLUSION: This study demonstrated for the first time that the CB1 cannabinoid receptor participates in the antinociceptive effect induced by EA.

The influence of the cannabinoid receptor CB1 on the periaqueductal gray in mice treated with photobiomodulation after chronic constriction injury of the sciatic nerve: a placebo-controlled trial / Influência do receptor canabinóide CB1 na substância cinzenta periaquedutal em camundongos tratados por fotobiomodulação após constrição crônica do nervo ciático: ensaio controlado por placebo

ABSTRACT BACKGROUND AND OBJECTIVES: Studies have demonstrated that the cannabinoid CB1 receptor is involved in the modulation of pain, mainly by activating the descending pain control pathway. However, the role of photobiomodulation in this process is not well elucidated. Thus, the present study aimed to investigate the involvement of the CB1 receptor in the supraspinal photobiomodulation-induced antinociception. METHODS: Male albino swiss mice were submitted to chronic constriction injury and treated with photobiomodulation. To evaluate the supraspinal involvement of the CB1 receptor in the photobiomodulation-induced antinociception, the cannabinoid CB1 receptor antagonist AM251 (0.1µg/vol 0.2µL) was injected 5 minutes before the photobiomodulation treatment. The photobiomodulation treatment was performed on the fifth day after the stereotactic surgery and chronic constriction injury at a dose of 50J/cm2 in acute condition. The hot plate and von Frey monofilaments tests were performed to evaluate the thermal and mechanical pain sensitivity, respectively. RESULTS: The thermal and mechanical nociceptive threshold was higher in mice with chronic constriction injury, injected with saline and treated with photobiomodulation at the dose of 50J/cm2 in both the hot plate (p<0.001) and von Frey (p>0.001) tests. These antinociceptive effects were not detected in mice with chronic constriction injury pre-treated with AM251. CONCLUSION: The present study suggests that CB1 receptors located in Supraspinal structures, participate in the control of neuropathic pain following photobiomodulation treatment in animals undergoing chronic constriction injury.

RESUMO JUSTIFICATIVA E OBJETIVOS: Estudos demonstraram que o receptor canabinóide CB1 está envolvido na modulação da dor, principalmente pela ativação da via descendente de controle da dor, porém o papel da fotobiomodulação nesse processo não é bem elucidado. Assim, o presente estudo teve como objetivo investigar o envolvimento do receptor CB1 na antinocicepção induzida pela fotobiomodulação a nível supraespinhal. MÉTODOS: Camundongos machos suíço albinos foram submetidos à lesão por constrição crônica e tratados com fotobiomodulação. Para avaliar o envolvimento supraespinhal do receptor CB1 na antinocicepção induzida por fotobiomodulação foi injetado o antagonista do receptor canabinóide CB1, AM251 (0,1µg/vol 0,2µL) 5 minutos antes do tratamento com fotobiomodulação. O tratamento de fotobiomodulação foi realizado no quinto dia após cirurgia estereotática e lesão por constrição crônica, na dose de 50J/cm2 em estado agudo. Os testes de placa quente e monofilamentos de von Frey foram realizados para avaliar a sensibilidade térmica e mecânica à dor, respectivamente. RESULTADOS: O limiar térmico e mecânico nociceptivo foi maior nos camundongos com lesão por constrição crônica, injetados com solução salina e tratados com fotobiomodulação na dose de 50J/cm2 nos testes de placa quente (p<0,001) e von Frey (p>0,001). Esses efeitos antinociceptivos não foram detectados em camundongos com lesão por constrição crônica tratados com AM251. CONCLUSÃO: O presente estudo sugere que os receptores CB1 localizados nas estruturas supraespinhais participam do controle da dor neuropática, após tratamento com fotobiomodulação em animais submetidos à lesão por constrição crônica.

Antinociceptive and anti-inflammatory effects of myricetin 3-O-ß-galactoside isolated from Davilla elliptica: involvement of the nitrergic system.

We aimed to study the antinociceptive effects of myricetin 3-O-ß-galactoside (Mi), a substance isolated from the hydroalcoholic extract of Davilla elliptica. This study examined male Swiss mice, inducible nitric oxide synthase C57B16/J knockout mice (iNOS(-/-)), and their corresponding wild type (WT). Formalin and tail-flick tests were used to evaluate the nociceptive threshold, and the carrageenan-induced paw edema test was used as a model for inflammation. The following drugs were administered to investigate the involvement of the nitrergic and opioidergic systems: L-NAME, a nonspecific nitric oxide synthase (NOS) inhibitor; L-arginine (L-Arg), a precursor for the synthesis of nitric oxide (NO); D-arginine (D-Arg), an inactive isomer for the synthesis of NO; aminoguanidine (Am), an inducible nitric oxide synthase (iNOS) inhibitor; and naloxone, a nonselective antagonist of opioid receptors. The results showed that oral pretreatment with Mi caused a dose-dependent inhibition of the inflammatory phase of the formalin test and did not alter motor performance. Intraperitoneal injection of L-NAME caused a reduction in the licking time during the second phase of the formalin test. The administration of L-Arg (but not D-Arg) reversed the antinociceptive effect of L-NAME. Furthermore, pre-administration of aminoguanidine potentiated the antinociceptive effect. Mi did not cause an antinociceptive effect in iNOS knockouts and led to a reduction in the nitrite concentration in the paws of mice. Carrageenan-induced paw edema was reduced in Swiss mice and WT mice when compared to iNOS(-/-) mice. Pre-administration of naloxone (NLX) did not reverse the antinociceptive effect of Mi, excluding the opioidergic system as a mediator of the antinociceptive effect. Thus, the results suggest that the antinociceptive and anti-inflammatory effects of myricetin 3-O-ß-galactoside are related to peripheral inhibition of nitric oxide synthesis, mainly iNOS.

Aplicação e comparação de duas equações preditas para o teste de caminhada de seis minutos em indivíduos hipertensos / Application and comparison of two predicted equations for the six-minute walk test in hypertensive subjects

Introdução: O Teste de Caminhada de 6 minutos (TC6) tem sido utilizado especialmente para mensurar a capacidade funcional e avaliar a eficiência de diversos tratamentos cardiovasculares. Objetivo: O objetivo do presente estudo foi aplicar e comparar as equações preditas do TC6, em indivíduos hipertensos participantes de reabilitação cardiovascular (RCV). Material e métodos: A amostra foi composta por 39 pacientes de ambos os sexos (masculino: 11 e feminino: 28) com média de idade 57,5 ± 11 anos portadores de hipertensão arterial. Resultados: Após o programa de RCV foi verificado um aumento significativo (p < 0,001) da distância caminhada no TC6 quando comparada aos valores antes da RCV (514,7 ± 100,6 x 382,4 ± 116,3 m). Entretanto, não houve diferença estatística quando comparado os valores preditos das duas equações. Conclusão: A distância percorrida no TC6 foi maior após a RCV quando comparada aos valores iniciais, demostrando que a RCV produz benefícios na capacidade funcional dessa população. Além disso, os resultados sugerem que as duas equações avaliadas, tem aplicabilidade semelhante para a população de indivíduos hipertensos brasileiros.

Introduction: The 6-minute Walk Test (6MWT) has been used especially to measure functional capacity, to evaluate the efficiency of various cardiovascular treatments. Objective: The objective of the present study was to apply and compare the predicted EQ6 equations in hypertensive individuals participating in cardiovascular rehabilitation (CR). Methods: The sample consisted of 39 patients of both sexes (male: 11 and female: 28) with mean age 57.5 ± 11 years old with arterial hypertension. Results: After the CR program, was verified a significant increase (p < 0.001) in the 6MWT when compared to values before of CR (514.7 ± 100.6 x 382.4 ± 116.3 m). However, there was no statistical difference when compared to the predicted values of the two equations. Conclusion: The distance walked on the 6MWT was higher after the RCV when compared to the initial values, showing that the RCV produces benefits in the functional capacity of this population. In addition, the results suggest that the two equations evaluated have similar applicability for the population of Brazilian hypertensive individuals.