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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.

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-1β 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.

Brainwave Entrainment (BWE) is a noninvasive method of neuromodulation based on the principle that auditory or visual stimulation at a specific frequency can lead the brain’s electrocortical activity to oscillate at the frequency of the external signal or its multiples. This phenomenon could be used to alter physiological and psychological states. Therefore, we conducted an integrative review to answer the question: “What are the observed benefits of BWE on human health and well-being?” We searched for studies published in the last ten years in the Directory of Open Access Journals (DOAJ), EMBASE, Virtual Health Library (BVS), PubMed, SciELO, and Cochrane Library databases in April 2024. Searches were conducted in English, Portuguese, and Spanish. A total of 84 studies were included in our review. Studies showed improvements in various conditions, such as pain, sleep disturbances, mood disorders, cognition, and neurodegenerative disorders. In conclusion, our findings align with previous reviews and underscore the need for further research on BWE, particularly with larger sample sizes, robust control groups, and randomized clinical trial designs. Nevertheless, BWE demonstrates promising therapeutic potential and may support the management of various health conditions, enhancing individuals' quality of life.

Physical therapists frequently use joint mobilization therapy techniques to treat people with musculoskeletal dysfunction and pain. Several studies suggest that endogenous adenosine may act in an analgesic fashion in various pain states. The purpose of this study was to investigate the contribution of the adenosinergic system on the antihyperalgesic effect of ankle joint mobilization (AJM). This was a experimental study. To test the hypothesis that the adrenosinergic system is involved in the antihyperalgesic effect of AJM, mice (25-35 g) submitted to plantar incision surgery were used as a model of acute postoperative pain. The mice were subjected to AJM for 9 minutes. Withdrawal frequency to mechanical stimuli was assessed 24 hours after plantar incision surgery and 30 minutes after AJM, adenosine, clonidine, or morphine treatments. The adenosinergic system was assessed by systemic (intraperitoneal), central (intrathecal), and peripheral (intraplantar) administration of caffeine. The participation of the A1 receptor was investigated using a selective adenosine A1 receptor subtype antagonist. In addition, previous data on the involvement of the serotonergic and noradrenergic systems in the antihyperalgesic effect of AJM were confirmed. Ankle joint mobilization decreased mechanical hyperalgesia, and this effect was reversed by pretreatment of the animals with caffeine given by intraperitoneal, intraplantar, and intrathecal routes. In addition, intraplanar and intrathecal administrations of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, a selective adenosine A1 subtype receptor antagonist) or systemic administration of yohimbine or ρ-chlorophenylalanine methyl ester hydrochloride (PCPA) blocked the antihyperalgesia induced by AJM. The results are limited to animal models and cannot be generalized to acute pain in humans. This study demonstrated the involvement of the adenosinergic system in the antihyperalgesic effect of AJM in a rodent model of pain and provides a possible mechanism basis for AJM-induced relief of acute pain.

Light-emitting diode therapy (LEDT) has been clinically used as an alternative to low-level laser therapy; nevertheless, the molecular basis for LEDT effects remains unclear. The objective of this study was to evaluate the analgesic effect of LEDT in the mouse plantar incision (PI) model of postoperative pain, as well as to investigate some of the possible mechanisms involved in this effect, i.e., peripheral and central opioid receptors; migration of opioid-containing leukocytes to PI site and the l -arginine/nitric oxide (NO) pathway. To that end, mice were subjected to PI and treated with LEDT (950 nm, 80 mW/cm 2 , 1 through 13 J/cm 2 ). Mechanical hypersensitivity was assessed as withdrawal frequency percentage to 10 presentations of a 0.4-g von Frey filament. In addition, the animals were pretreated with systemic (i.p.), intra-plantar (i.pl.), or intrathecal injection (i.t) of naloxone (a nonselective opioid receptor antagonist; 1 mg/kg, i.p.; 5 μg/right paw or 5 μg/site, respectively) or a systemic injection of fucoidin (100 μg/mouse, i.p., an inhibitor of leukocyte rolling through binding to l- and p -selectins). Our results demonstrate, for the first time, that LEDT induced a dose–response analgesic effect in the model of PI in mice. At the dose of 9 J/cm 2 LEDT presented the most significant results through (1) activation of peripheral opioid receptors which involve, at least partially, the recruitment of opioid-containing leukocytes to the PI site and; (2) activation of the l -arginine/NO pathway. These results extend previous literature data and suggest that LEDT might be useful in the treatment of postoperative pain.

Stationary cycling is the popular, preferred, and convenient form of exercise. During exercise, autonomic modulation is seen which can be assessed by heart rate variability (HRV). The aim of the study was to evaluate the changes in HRV during mild-intensity cycling exercise. An observational cross-sectional study was done on 20 healthy male volunteers with the age (35.44 ± 4.12), height (71.12 ± 11.98), and weight (161.23 ± 11.65), BMI (27.12 ± 3.49) attending various YOGA sessions in AYUSH OPD. Volunteers underwent an exercise program at the mild intensity of 30% to 50% of maximal heart rate on a stationary cycle for 20 min. HRV was recorded by the HRV mobile unit Dynamika Machine at rest, every 5 min (4×) over 20 min and during the recovery period. Repeated measures of analysis of variance with post-hoc analysis with Bonferroni and Holm's multiple comparisons. Significant change was observed in mean heart rate and time domain parameters. Frequency domain parameters that showed significant change were total power, High Frequency- HF (ms ), Very Low Frequency -VLF (ms ), Low Frequency -LF (ms ), and Very Low Frequency %-VLF (%). The HRV parameters conclusively point towards cardiac parasympathetic withdrawal and sympathetic dominance at the initiation of exercise. With the progression of exercise, the sympathetic influence is retained. In the recovery period parasympathetic reactivation gains control over heart rate as well as HRV. The HRV response to exercise challenges may be helpful in designing exercise programs based on variations in the autonomic response.

The gut microbiota is known to interact with various organs in the body, including the central nervous system, through the gut-brain axis. Intestinal dysbiosis can lead to increased peripheral inflammation and, consequently, affect the brain, resulting in neuroinflammation. Photobiomodulation (PBM) has demonstrated positive regulatory effects on the imbalance of certain body functions, including pain, inflammation, immunity, wound healing, and gut microbiota dysbiosis. Therefore, PBM at the intestinal level could help improve intestinal dysbiosis and reestablish cerebral homeostasis. In this context, this study aimed to conduct a narrative review of the literature on the effects of PBM at the intestinal level on intestinal dysbiosis and neuroinflammation. Overall, the findings highlight that PBM modulates the gut microbiota, suggesting it could serve as a therapy for neurological conditions affecting the gut-brain axis. Future research should focus on further elucidating the molecular mechanisms underlying this therapy.

AbstractTo verify the influence of ozone (O3) therapy on an experimental model of rheumatoid arthritis (RA), 30 male Wistar rats were randomly allocated to 2 groups, control (C) and treatment (T), and subdivided into control (C12, C48, C72) and treatment (T12, T48, T72) groups. RA was induced by administration of collagenase plus complete Freud’s adjuvant in the knee joint region. The animals were treated with ozone therapy (1 ml O3 injection in the knee i.a.) according to group assignment: T12, 2 h; T48, 2 and 24 h; and T72, 2, 24, and 48 h post-RA induction. The different animal groups were euthanized 12, 24, or 72 h post-RA induction, respectively. Synovial exudate levels of IL-10, IL-12p70, TNF-α, INF-γ, and MCP-1 were assessed by flow cytometry, and histopathological analysis of the knee cartilage was conducted. Ozone therapy effectively decreases inflammation, reducing IL-12 and TNF-α, and increasing IL10. O3 did not statistically affect INF-γ or MCP-1 levels. More expressive results were obtained with group T72, i.e., treated 2, 24, and 48 h post-RA induction, which indicates that longer-term ozone treatment is more effective than a single acute application. Ozone therapy effectively reduced inflammation with effects, at least in part, mediated through reduction of pro-inflammatory cytokines and activation of IL-10 anti-inflammatory cytokine.

The pro-resolving mechanism is a recently described endogenous process that controls inflammation. The present study evaluated components of this mechanism, including annexin 1 (ANXA1) and the formyl peptide receptor 2/ALX (FPR2/ALX) receptor, in the antihyperalgesic effect induced by electroacupuncture (EA) in an animal model of persistent peripheral inflammation. Male Swiss mice underwent intraplantar (i.pl.) injection with complete Freund’s adjuvant (CFA). Mechanical hyperalgesia was assessed with von Frey monofilaments. Animals were treated with EA (2–10 Hz, ST36-SP6) or subcutaneous BML-111 injection (FPR2/ALX agonist) for 5 consecutive days. In a separate set of experiments, on the first and fifth days after CFA injection, animals received i.pl. WRW4 (FPR2/ALX antagonist) or naloxone (non-selective opioid receptor antagonist) before EA or BML-111 injection. Paw protein levels of FPR2/ALX and ANXA1 were evaluated on the second day after CFA injection by western blotting technique. EA and BML-111 reduced mechanical hyperalgesia. I.pl. naloxone or WRW4 prevented the antihyperalgesic effect induced by either EA or BML-111. EA increased ANXA1 but did not alter FPR2/ALX receptor levels in the paw. Furthermore, i.pl. pretreatment with WRW4 prevented the increase of ANXA1 levels induced by EA. This work demonstrates that the EA antihyperalgesic effect on inflammatory pain involves the ANXA1/FPR2/ALX pro-resolution pathway. This effect appears to be triggered by the activation of FPR2/ALX receptors and crosstalk communication with the opioid system.

We investigated the effects of two common recovery methods; far-infrared emitting ceramic materials (Bioceramic) or cold-water immersion on muscular function and damage after a soccer match. Twenty-five university-level soccer players were randomized into Bioceramic (BIO; n = 8), Cold-water immersion (CWI; n = 9), or Control (CON; n = 8) groups. Heart rate [HR], rating of perceived exertion [RPE], and activity profile through Global Positioning Satellite Systems were measured during the match. Biochemical (thiobarbituric acid reactive species [TBARS], superoxide dismutase [SOD], creatine kinase [CK], lactate dehydrogenase [LDH]), neuromuscular (countermovement [CMJ] and squat jump [SJ], sprints [20-m]), and perceptual markers (delayed-onset muscle soreness [DOMS], and the perceived recovery scale [PRS]) were assessed at pre, post, 24 h, and 48 h post-match. One-way ANOVA was used to compare anthropometric and match performance data. A two-way ANOVA with post-hoc tests compared the timeline of recovery measures. No significant differences existed between groups for anthropometric or match load measures (P > 0.05). Significant post-match increases were observed in SOD, and decreases in TBARS in all groups (p < 0.05), without differences between conditions (p > 0.05). Significant increases in CK, LDH, quadriceps and hamstring DOMS (p < 0.05), as well as decreases in 20-m, SJ, CMJ, and PRS were observed post-match in all groups (p < 0.05), without significant differences between conditions (p > 0.05). Despite the expected post-match muscle damage and impaired performance, neither Bioceramic nor CWI interventions improved post-match recovery.