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.

Preventive Supplementation of Omega-3 Reduces Pain and Pro-inflammatory Cytokines in a Mouse Model of Complex Regional Pain Syndrome Type I.

Complex regional pain syndrome type I (CRPS-I) is a condition that responds poorly to treatments. The role of omega-3 fatty acids in the treatment of inflammatory disorders is well described in the literature; however, few studies have evaluated its therapeutic benefits in different types of pain. We evaluated the potential antihyperalgesic and anti-inflammatory effects of preventive omega-3 supplementation in an animal model of CRPS-I. In experiment 1, Swiss female mice were supplemented for 30 days with omega-3 before the induction of the CRPS-I model and 14 days after. Mechanical hyperalgesia was evaluated at baseline and from the 4th to the 14th day after CPRS-I induction along with open field locomotor activity after 30 days of supplementation. In experiment 2, Swiss female mice were supplemented for 30 days with omega-3 and then subjected to the CRPS-I model. Twenty-four hours later the animals were euthanized, and tissue samples of the spinal cord and right posterior paw muscle were taken to measure pro-inflammatory cytokine TNF and IL-1ß concentrations. Omega-3 supplementation produced antihyperalgesic and anti-inflammatory effects, as well as reducing pro-inflammatory cytokine concentrations, without altering the animals' locomotion. No open field locomotor changes were found. The 30-day supplementation at the tested dose was effective in the CRPS-I model.

Decrease of IL-1ß and TNF in the Spinal Cord Mediates Analgesia Produced by Ankle Joint Mobilization in Complete Freund Adjuvant-Induced Inflammation Mice Model.

OBJECTIVE: This study aims to investigate the effects of ankle joint mobilization (AJM) on mechanical hyperalgesia and peripheral and central inflammatory biomarkers after intraplantar (i.pl.) Complete Freund's Adjuvant (CFA)-induced inflammation. METHODS: Male Swiss mice were randomly assigned to 3 groups (n = 7): Saline/Sham, CFA/Sham, and CFA/AJM. Five AJM sessions were carried out at 6, 24, 48, 72, and 96 h after CFA injection. von Frey test was used to assess mechanical hyperalgesia. Tissues from paw skin, paw muscle and spinal cord were collected to measure pro-inflammatory (TNF, IL-1ß) and anti-inflammatory cytokines (IL-4, IL-10, and TGF-ß1) by ELISA. The macrophage phenotype at the inflammation site was evaluated by Western blotting assay using the Nitric Oxide Synthase 2 (NOS 2) and Arginase-1 immunocontent to identify M1 and M2 macrophages, respectively. RESULTS: Our results confirm a consistent analgesic effect of AJM following the second treatment session. AJM did not change cytokines levels at the inflammatory site, although it promoted a reduction in M2 macrophages. Also, there was a reduction in the levels of pro-inflammatory cytokines IL-1ß and TNF in the spinal cord. CONCLUSION: Taken together, the results confirm the anti-hyperalgesic effect of AJM and suggest a central neuroimmunomodulatory effect in a model of persistent inflammation targeting the pro-inflammatory cytokines IL-1ß and TNF.

Lavandula angustifolia essential oil inhalation reduces mechanical hyperalgesia in a model of inflammatory and neuropathic pain: The involvement of opioid and cannabinoid receptors.

Lavandula angustifolia (LaEO) essential oil has been widely used by aromatherapy in the treatment of various clinical conditions, with evidence of its analgesic and anti-inflammatory potential. Our results demonstrate that sixty-five substances were identified in LaEO. Among the compounds found, the major ones were linalool (30.61%) and linalyl acetate (20.36%). We found that LaEO inhalation reduces mechanical hyperalgesia in conditions of chronic inflammatory and neuropathic pain. Furthermore, this effect seems to be mediated by peripheral and central opioid and cannabinoid 2 receptors. The findings of the present study suggests that the LaEO inhalation is effective on the chronic pain treatment.

Effects of core strengthening on balance in university judo athletes.

BACKGROUND: Core strengthening prepares the body in an integral, safe and efficient way, favoring balance and postural control; physical abilities constantly demanded in sports, especially in body contact modalities, such as Judo. OBJECTIVE: This study investigated the effects of core strengthening on balance in university judo athletes. METHODS: Eighteen athletes from the University of Southern Santa Catarina (UNISUL) were randomly allocated into two groups: experimental (n = 9) and control (n = 9). Experimental group athletes were submitted to a core strengthening protocol (30-min sessions, twice a week for 5 consecutive weeks). Evaluations consisted of Stabilometic (center of pressure behavior parameters: total area in mm2, laterolateral and anteroposterior width in mm) and baropodometric analysis [peak pressure: obtained during a 30-s acquisition period and expressed by foot area, i.e., (a) forefoot (metatarsal heads and toes); and (b) hindfoot (calcaneus region, distal third of the foot)]. Right/left foot ratios were calculated as relative percentages and used for the analysis. The analyzes were performed at baseline and after 5 weeks of core strengthening. The athletes were evaluated in two situations: eyes-open and eyes-closed. RESULTS: Total right/left foot ratio pressure, right/left fore and hindfoot ratio pressure, as well as anteroposterior width measurements were statistically smaller in the experimental group. CONCLUSION: Although the results obtained showed that core strengthening presents certain benefits, these data alone are not enough to confirm its effects upon postural oscillation in university judo athletes.

Dietary supplementation with procyanidin-rich Pinus pinaster extract is associated with attenuated Ehrlich tumor development in mice.

Inflammation and oxidative stress are related to cancer initiation and progression. We hypothesized that dietary supplementation with a procyanidin-rich Pinus pinaster extract (Pyc) with known antioxidant and anti-inflammatory effects could induce systemic protection, thereby attenuating tumor development. To test our hypothesis, mice were subjected to long-term supplementation (20 days, every 24 h) with saline, 25 mg/kg resveratrol or 100 mg/kg Pyc. Pyc was administered at a maximum tolerated oral dose, previously determined using toxicity indicators. Ten days after Ehrlich ascites tumor induction, weight gain and abdominal circumference increase were calculated. Ascitic fluid from six mice/group was evaluated by determining total volume; tumor packed cell volume; cell viability; tumor cell death type; inflammatory infiltrate; and levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), carbonyl proteins, lipid peroxidation, cyclooxigenase-2 (COX-2) expression and Akt phosphorylation (p-Akt). Ten mice/group were monitored to evaluate survival. Pyc and resveratrol were associated with reduced weight gain (>30%), abdominal circumference and ascitic volume. Tumor packed cell volume was reduced in Pyc-supplemented mice (26%), which had the largest tumor cell count reduction (>35%), increased ascitic fluid apoptosis rates (20%) and the longest survival (>2-fold). Pyc and resveratrol treatment both reduced inflammatory infiltrate and levels of TNF-α, IL-1ß, carbonyl proteins, lipid peroxidation (~ 30%) and p-Akt (up to 4-fold). Only Pyc significantly inhibited COX-2. Pyc attenuated oxidative and inflammation mediators and impaired tumor development, supporting our hypothesis and suggesting Pyc as a candidate for future studies in multitargeted dietary-based cancer prevention approaches.

Antioxidant Effect of Far Infrared Radiation Produced by Bioceramics in Individuals with Intermittent Claudication: A Randomized, Controlled Pilot Study.

BACKGROUND: Biomedical research has recently incorporated bioceramics applications into new health care approaches. OBJECTIVE: This study evaluated the effect of far infrared-emitting bioceramics wraps in the treatment of intermittent claudication. METHODS: This is a randomized double-blind placebo-controlled pilot study. Thirty-five patients met the criteria and were randomized into either control (placebo wraps) or bioceramics group (far infrared emitting-ceramics wraps) and assessed over a 90-day period for the following outcomes: six-minute walk test (6MWT), ankle-brachial index (ABI), Flow-mediated arterial dilation (FMD), quality of life and claudication. Oxidative stress and inflammatory biomarkers were measured in plasma of patients. RESULTS: Intervention induced a decrease in oxidative stress, with significant lower levels of reactive substances to thiobarbituric acid (TBARS), as well as increase in superoxide dismutase and catalase enzyme activities. There was an increase in the environment subscale of the quality of life questionnaire. No statistically significant differences were found in the inflammatory cytokines, 6MWT, ABI and FMV evaluations. CONCLUSIONS: In Sum, FIR treatment improved oxidative stress profile and quality-of-life of patients with intermittent claudication. The study was registered into the ensaiosclinicos.gov.br (Registro Brasileiro de Ensaios Clínicos [ReBEC]) (RBR-7nr6sy register number).

Correction to: Electroacupuncture induces antihyperalgesic effect through endothelin-B receptor in the chronic phase of a mouse model of complex regional pain syndrome type I.

The original version of this article contains an error. The Author Francisco José Cidral-Filho incorrectly listed as Francisco José Cidra-Filho. The correct spelling is presented above. The original article has been corrected.

Electroacupuncture induces antihyperalgesic effect through endothelin-B receptor in the chronic phase of a mouse model of complex regional pain syndrome type I.

Complex regional pain syndrome (CRPS) is a disorder that involves abnormal inflammation and nerve dysfunction frequently resistant to a broad range of treatments. Peripheral nerve stimulation with electroacupuncture (EA) has been widely used in different clinical conditions to control pain and inflammation; however, the use of EA in the treatment of CRPS is under investigation. In this study, we explore the effects of EA on hyperalgesia and edema induced in an animal model of chronic post-ischemia pain (CPIP model) and the possible involvement of endothelin receptor type B (ETB) in this effect. Female Swiss mice were subjected to 3 h hind paw ischemia/reperfusion CPIP model. EA treatment produced time-dependent inhibition of mechanical and cold hyperalgesia, as well as edema in CPIP mice. Peripheral administration (i.pl.) of BQ-788 (10 nmol), an ETB antagonist, prevented EA-induced antihyperalgesia while intrathecal administration prolonged EA's effect. Additionally, peripheral pre-treatment with sarafotoxin (SRTX S6c, 30 pmol, ETB agonist) increased EA anti-hyperalgesic effect. Furthermore, the expression of peripheral ETB receptors was increased after EA treatments, as measured by western blot. These results may suggest that EA's analgesic effect is synergic with ETB receptor activation in the periphery, as well as central (spinal cord) ETB receptor blockade. These data support the use of EA as a nonpharmacological approach for the management of CRPS-I, in an adjuvant manner to ETB receptor targeting drugs.

Far infrared-emitting ceramics decrease Freund's adjuvant-induced inflammatory hyperalgesia in mice through cytokine modulation and activation of peripheral inhibitory neuroreceptors.

OBJECTIVE: The present study aimed to evaluate the analgesic and anti-inflammatory effects of far infrared-emitting ceramics (cFIRs) in a model of persistent inflammatory hyperalgesia and to elucidate the possible mechanisms of these effects. METHODS: Mice were injected with complete Freund's adjuvant (CFA) and treated with cFIRs via placement on a pad impregnated with cFIRs on the bottom of the housing unit for different periods of time. Mice underwent mechanical hyperalgesia and edema assessments, and tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-10 levels were measured. Twenty-four hours after CFA injection and 30 min before cFIR treatment, mice were pretreated with a nonselective adenosinergic antagonist, caffeine, the selective adenosine receptor A1 antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), the selective cannabinoid receptor type 1 antagonist, AM281, the selective cannabinoid receptor type 2 antagonist, AM630, or the nonselective opioid receptor antagonist, naloxone, and mechanical hyperalgesia was assessed. RESULTS: cFIRs statistically (P < 0.05) decreased CFA-induced mechanical hyperalgesia ((82.86 ±â€¯5.21)% in control group vs (56.67 ±â€¯9.54)% in cFIR group) and edema ((1699.0 ±â€¯77.8) µm in control group vs (988.7 ±â€¯107.6) µm in cFIR group). cFIRs statistically (P < 0.05) reduced TNF-α ((0.478 ±â€¯0.072) pg/mg of protein in control group vs (0.273 ±â€¯0.055) pg/mg of protein in cFIR group) and IL-1ß ((95.81 ±â€¯3.95) pg/mg of protein in control group vs (80.61 ±â€¯4.71) pg/mg of protein in cFIR group) levels and statistically (P < 0.05) increased IL-10 ((18.32 ±â€¯0.78) pg/mg of protein in control group vs (25.89 ±â€¯1.23) pg/mg of protein in cFIR group) levels in post-CFA-injected paws. Peripheral pre-administration of inhibitory neuroreceptor antagonists (caffeine, DPCPX, AM281, AM630 and naloxone) prevented the analgesic effects of cFIRs (P < 0.05). CONCLUSION: These data provide additional support for the use of cFIRs in the treatment of painful inflammatory conditions and contribute to our understanding of the neurobiological mechanisms of the therapeutic effects of cFIRs.

A non-reflexive method based on the variability of temperature and bioimpedance in measuring inflammatory hyperalgesia and analgesia in mice.

BACKGROUND: Preclinical studies measure withdrawal responses to evoking thermal and mechanical stimuli instead of the more clinically important spontaneous pain. NEW METHOD: Therefore, we studied the effect of peripheral inflammation induced by intraplantar administration of complete Freund's adjuvant (CFA) in mice on the variability of temperature and bioimpedance as an index of pain produced by inflammation. To this end, we initially determined mathematical scores based on changes in temperature and bioimpedance (STB) for animals with an inflamed paw and compared these scores with commonly used measures of inflammatory pain. We then pharmacologically validated the tool using dexamethasone. RESULTS: The STB analysis resembled the response found in the von Frey Hair (vFH) test. The CFA-induced increase in STB and vFH tests were reversed by intraperitoneal administration of dexamethasone. The correlation between the STB and vFH measurements showed a high correlation coefficient (R2 = 0.911, p < 0.001). COMPARISON WITH EXISTING METHOD: Our results also demonstrated that CFA paw injection induced mechanical hyperalgesia in mice and remained virtually unaltered during all time-points tested for 5 days, as measured with vFHs. The administration of CFA into the paw induced a large increase in paw volume that was apparent 1 and 5 days after the injection. The CFA injection resulted in a significant (p < 0.05) decrease in the response latency to the heat stimulus, as evaluated on day 4 post-CFA injection. CONCLUSIONS: The data presented here suggest that STB may provide a novel non-invasive approach for inflammatory pain detection.

Foot Reflexotherapy Induces Analgesia in Elderly Individuals with Low Back Pain: A Randomized, Double-Blind, Controlled Pilot Study.

INTRODUCTION: This study evaluated the effects of foot reflexotherapy on pain and postural balance in elderly individuals with low back pain. DESIGN: Randomized, controlled pilot study. Participants (n = 20) were randomly assigned to 2 groups: individuals submitted to conventional foot massage (control group) or foot reflexotherapy (RT, intervention group) for a period of 5 weeks. Questionnaires on pain and disability (visual analogue scale [VAS] and Roland-Morris Disability Questionnaire [RMDQ]), heart rate variability, and orthostatic balance and baropodometric analysis were assessed at two intervals: before and after intervention. RESULTS: RT group showed statistically significant differences when compared to control group in the following parameters: decrease in VAS scores for pain throughout the study, decrease in parasympathetic activity, and improvement in RMDQ scores. The two groups did not statistically differ in either orthostatic balance or baropodometric analyses. CONCLUSION: This study demonstrated that foot reflexotherapy induced analgesia but did not affect postural balance in elderly individuals with low back pain.