Efeitos da eletroacupuntura na dor pós isquemia crônica da pata em camundongos: avaliação da participação do receptor ETb periférico e espinal

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Neurociências, Florianópolis, 2018A Síndrome da Dor Regional Complexa do tipo I (SDRC-I) possui perfilrefratário à diversas formas de tratamentos. Deste modo, tratamentosintegrativos como a eletroacupuntura (EA) de baixa frequência vêmsendo propostos para minimizar a dor em diferentes modelos animais eclínicos. Neste estudo, foi testado o efeito da EA no modelo animal dedor pós isquemia crônica (DPIC), o qual mimetiza os sinais e sintomasda SDRC-I em humanos, bem como avaliado o mecanismo de açãoenvolvido neste efeito. Camundongos Swiss fêmeas (n = 8 por grupo)foram submetidas a isquemia e reperfusão (IR) da pata traseira direitapor meio de um torniquete no tornozelo, após 3 h o anel elástico foiretirado, permitindo a reperfusão da pata. O modelo animal induziuhiperalgesia mecânica e ao frio, assim como edema na pata traseiradireita dos animais. O tratamento único com EA de baixa frequência nosacupontos ST36 e SP6 ipsilateral a IR da pata no 3º, 7º, 14º e 21º diaapós IR da pata, sendo avaliado o decurso temporal do efeito antihiperalgésicoda EA em cada dia. As avaliações da hiperalgesiamecânica e os tratamentos diários foram realizados do 7º ao 14º dia oudo 14º ao 21º dia, edema e temperatura da pata do 1º ao 3º dia. Aavaliação dos receptores ETB periféricos e espinais foram avaliados no14º dia após a IR, por meio do bloqueio farmacológico (Bq-788antagonista para o receptor ETB) e da análise da expressão dessereceptor. Os resultados demonstraram que a EA reduziu a hiperalgesiamecânica e ao frio em todos os dias avaliados. A EA também reduziu oedema, mas não a temperatura da pata. A expressão dos receptores ETBperiféricos, mas não espinais foi aumentado pela EA. Considerando oconjunto de dados obtidos o presente trabalho sugere que a EA pode serutilizada como tratamento adjuvante para os sinais e sintomas presentesna DPIC, como a hiperalgesia mecânica e ao frio e edema; além disso osreceptores ETB periféricos e espinais parecem mediar, pelo menos emparte, o efeito anti-hiperagésico da EA.Abstract : The Complex Regional Pain Syndrome Type I (CRPS-I) has a refractoryprofile to various forms of treatments. Thus, integrative treatments suchas low frequency electroacupuncture (EA) have been proposed tominimize pain in different experimental and clinical models. In thisstudy, the effect of EA was tested in the Chronic Postischemic PainModel (CPIP), which mimics the signs and symptoms of CRPS-I inhumans, as well as evaluated the mechanism of action involved in thiseffect. Female Swiss mice (n=8 per group) were submitted to ischemiaand reperfusion (IR) of the right hind paw by an ankle tourniquet, 3 hafter the elastic ring was removed, allowing the paw reperfusion. Theexperimental model induced mechanical and cold hyperalgesia andedema in the right hind paw of the animals. The single treatment withlow frequency EA in ST36 and SP6 acupoints ipsilateral to hind paw IRat the 3rd, 7th, 14th and 21st day after hind paw IR, and the temporalcourse of the antihyperalgesic effect of EA on each day was evaluated.The evaluations of mechanical hyperalgesia and daily treatments wereperformed from the 7th to the 14th day or from the 14th to the 21st dayand edema and paw temperature from the 1st to the 3rd day. Theevaluation of peripheral and spinal ETB receptors was evaluated on the14th day after IR, using pharmacological blockade (Bq-788 antagonistfor the ETB receptor) and analysis of the receptor expression. The resultsdemonstrated that EA reduced mechanical and cold hyperalgesia on alldays that were evaluated. EA also reduced edema, but not pawtemperature. The expression of peripheral but not spinal ETB receptorswere increased by EA. Considering the dataset obtained the presentwork suggests that the EA can be used as an adjuvant treatment for thesigns and symptoms present in the CRPS-I, such as mechanical and coldhyperalgesia and edema; in addition, peripheral and spinal ETBreceptors appear to mediate, at least in part, the antihyperagic effect ofEA

Gentle Touch Therapy, Pain Relief and Neuroplasticity at Baseline in Fibromyalgia Syndrome: A Randomized, Multicenter Trial with Six-Month Follow-Up

Background: Fibromyalgia (FM) is considered a stress-related disorder characterized mainly by chronic widespread pain. Its pathogenesis is unknown, but cumulative evidence points at dysfunctional transmitter systems and inflammatory biomarkers that may underlie the major symptoms of the condition. This study aimed to evaluate pain scores (primary outcome), quality of life, inflammatory biomarkers and neurotransmitter systems in women with FM (secondary outcomes) subjected to gentle touch therapy (GTT) or placebo. Methods: A total of 64 female patients with FM were randomly assigned to two groups, namely GTT (n = 32) or Placebo (n = 32). Clinical assessments were conducted at baseline and post-intervention with six-month follow-up. We measured serum catecholamines (dopamine), indolamines and intermediary metabolites (serotonin or 5-hydroxyindolacetic acid (5-HIAA)), as well as tetrahydrobiopterin (BH4), which is a cofactor for the synthesis of neurotransmitters and inflammatory biomarkers in women with FM. A group of healthy individuals with no intervention (control group) was used to compare biochemical measurements. Intervention effects were analyzed using repeated measures (RM) two-way ANOVA followed by Bonferroni post hoc test and mixed ANCOVA model with intention to treat. Results: Compared to placebo, the GTT group presented lower pain scores and brain-derived neurotrophic factor (BDNF) levels without altering the quality of life of women with FM. Changes in BDNF had a mediating role in pain. Higher baseline serum BDNF and 5-HIAA or those with a history of anxiety disorder showed a higher reduction in pain scores across time. However, women with higher serum dopamine levels at baseline showed a lower effect of the intervention across the observation period revealed by an ANCOVA mixed model. Conclusions: In conclusion, lower pain scores were observed in the GTT group compared to the placebo group without altering the quality of life in women with FM. Reductions in BDNF levels could be a mechanism of FM pain status improvement. In this sense, the present study encourages the use of these GTT techniques as an integrative and complementary treatment of FM