Electroacupuncture decreases inflammatory pain through a pro-resolving mechanism involving the peripheral annexin A1-formyl peptide receptor 2/ALX-opioid receptor pathway.

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.

Post-Match Recovery in Soccer with Far-Infrared Emitting Ceramic Material or Cold-Water Immersion.

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.

Effects of Far-Infrared Emitting Ceramic Materials on Recovery During 2-Week Preseason of Elite Futsal Players.

Nunes, RFH, Cidral-Filho, FJ, Flores, LJF, Nakamura, FY, Rodriguez, HFM, Bobinski, F, De Sousa, A, Petronilho, F, Danielski, LG, Martins, MM, Martins, DF, and Guglielmo, LGA. Effects of far-infrared emitting ceramic materials on recovery during 2-week preseason of elite futsal players. J Strength Cond Res 34(1): 235-248, 2020-We investigated the effects of far-infrared emitting ceramic materials (cFIR) during overnight sleep on neuromuscular, biochemical and perceptual markers in futsal players. Twenty athletes performed a 2-week preseason training program and during sleep wore bioceramic (BIO; n = 10) or placebo pants (PL; n = 10). Performance (countermovement jump [CMJ]; squat jump [SJ]; sprints 5, 10, and 15-m) and biochemical markers (tumor necrosis factor alpha-TNF-α, interleukin 10-IL-10, thiobarbituric acid-reactive species [TBARS], carbonyl, superoxide dismutase [SOD], catalase [CAT]) were obtained at baseline and after the 1st and 2nd week of training. Delayed-onset muscle soreness (DOMS) and training strain were monitored throughout. Changes in ΔCMJ and ΔSJ were possibly (60/36/4 [week-1]) and likely (76/22/2 [week-2]) higher in BIO. Both groups were faster in 5-m sprint in week 2 compared with baseline (p = 0.015), furthermore, BIO was likely faster in 10-m sprint (3/25/72 [week 1]). Significant group × time interaction in %ΔTNF-α were observed (p = 0.024 [week-1]; p = 0.021 [week-2]) with values possibly (53/44/3 [week 1]) and likely (80/19/1 [week 2]) higher in BIO. The %ΔIL-10 decreased across weeks compared with baseline (p = 0.019 [week-1]; p = 0.026 [week-2]), showing values likely higher in BIO (81/16/3 [week-1]; 80/17/3 [week-2]). Significant weekly increases in %ΔTBARS (p = 0.001 [week-1]; p = 0.011 [week-2]) and %ΔCarbonyl (p = 0.002 [week-1]; p < 0.001 [week-2]) were observed compared with baseline, showing likely (91/5/4 [week-1]) and possibly (68/30/2 [week-2]) higher changes in BIO. Significant weekly decreases in %ΔSOD were observed compared with baseline (p = 0.046 [week 1]; p = 0.011 [week-2]), and between week 2 and week 1 (p = 0.021), in addition to significant decreases in %ΔCAT compared with baseline (p = 0.070 [week 1]; p = 0.012 [week 2]). Training strain (p = 0.021; very -likely [0/2/98]; week 1) and DOMS was lower in BIO (likely; 7 sessions) with differences over time (p = 0.001). The results suggest that the daily use of cFIR clothing could facilitate recovery, especially on perceptual markers during the early phases of an intensive training period.

Light-emitting diode therapy induces analgesia in a mouse model of postoperative pain through activation of peripheral opioid receptors and the L-arginine/nitric oxide pathway.

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.

ST36 laser acupuncture reduces pain-related behavior in rats: involvement of the opioidergic and serotonergic systems.

Laser acupuncture is a modality of low-level light therapy used as an alternative to needling for the past three decades. Although it has proved effective for the treatment of various conditions, the mechanisms underlying its effects are not fully understood. To contribute to this understanding, this study was designed to (1) evaluate the antinociceptive effect of ST36 laser acupuncture (830 nm, 3 J/cm(2)) in rat models of acute nociception and (2) to investigate the opioidergic and serotonergic systems involvement in this effect. Our results demonstrate that ST36 laser acupuncture inhibited (36 ± 2 %) acetic acid-induced abdominal constrictions and both neurogenic (48 ± 7 %) and inflammatory (phase IIA 42 ± 8 % and phase IIB 83 ± 6 %) phases of formalin-induced nociceptive behavior. Moreover, the antinociceptive activity of laser irradiation in the acetic acid test was significantly reversed by preadministration of naloxone (1 mg/kg, nonselective opioid receptor antagonist), pindolol (1 mg/kg, subcutaneous; nonselective 5-HT 1A/B receptor antagonist), and ketanserin (1 mg/kg; selective 5-HT2A receptor antagonist) but not by ondansetron (1 mg/kg, selective 5-HT3 receptor antagonist). Taken together, our data demonstrate, for the first time, that (1) ST36 laser acupuncture elicited significant antinociceptive effect against acetic acid- and formalin-induced behavior in rats and that (2) this effect is mediated by activation of the opioidergic and serotonergic (5-HT1 and 5-HT2A receptors) systems.

Ankle joint mobilization decreases hypersensitivity by activation of peripheral opioid receptors in a mouse model of postoperative pain.

OBJECTIVE: Investigate whether ankle joint mobilization (AJM) decreases hypersensitivity in the mouse plantar incision (PI) model of postoperative pain as well as to analyze the possible mechanisms involved in this effect. DESIGN: Experiment 1: PI male Swiss mice (25-35 g, N = eight animals per group) were subjected to five sessions of AJM, each lasting either 9 or 3 minutes. AJM movement was applied at a grade III as defined by Maitland. Paw withdrawal frequency to mechanical stimuli was assessed before realization of PI and before and after daily AJM sessions. Mechanical hypersensitivity was also assessed following systemic (intraperitoneal [i.p.]) and local (intraplantar) injection of naloxone (a nonselective opioid receptor antagonist; 1 mg/kg, i.p.; 5 µg/paw, respectively, experiment 2); and systemic injection of fucoidin (100 µg/mouse, i.p., an inhibitor of leukocyte rolling, experiment 3) in different groups of mice. RESULTS: Nine but not 3 minutes of AJM reduced mechanical hypersensitivity caused by PI, an effect that was prevented by systemic and local administrations of naloxone but not by fucoidin. CONCLUSIONS: Our results indicate that joint mobilization reduces postoperative pain by activation of the peripheral opioid pathway. However, antihypersensitivity induced by AJM is apparently not limited by the number of opioid-containing leukocytes but by opioid receptors availability in sensory neurons. A better understanding of the peripheral mechanisms of AJM could stimulate therapists to integrate joint mobilization with strategies also known to influence endogenous pain control, such as exercise, acupuncture, and transcutaneous electrical nerve stimulation to potentiate endogenous analgesia.

Acupuncture reduces peripheral and brainstem cytokines in rats subjected to lipopolysaccharide-induced inflammation.

BACKGROUND: Lipopolysaccharide (LPS) endotoxins are activators of innate immunity inducing infection and inflammatory responses. Anti-inflammatory drugs can have undesirable side effects. Acupuncture may be an alternative for the treatment of inflammatory processes. OBJECTIVE: We investigated the potential anti-inflammatory effect of manual acupuncture (MA) at SP6 upon LPS-induced peritonitis in rats. METHODS: Peritonitis was induced in rats with an intraperitoneal injection of LPS (0.002, 0.02, 0.2 or 2 µg/kg) in four experimental groups (n = 6 each). A fifth group was injected with sterile saline solution (saline group, n = 6). Four hours after the procedure, peritoneal fluid was collected to determine total cell counts for inflammatory cells, differential leukocyte counts and peritoneal capillary permeability. The LPS dose of 0.02 µg/kg was used in the subsequent experiments as it most successfully induced peritoneal inflammation. Subsequently, five experimental groups (n = 12 rats each) were used: (1) saline, (2) control (untreated LPS group), (3) indomethacin (LPS group treated with indomethacin), (4) NA (LPS group treated with MA at a location not corresponding to any traditional acupuncture point), and (5) SP6 (LPS group treated with verum MA at SP6). Ten minutes after MA or 30 min after indomethacin treatment, the rats received an intraperitoneal injection of LPS. After 4 h, total leukocyte and differential cell counts, myeloperoxidase (MPO) activity, vascular permeability and cytokine levels were evaluated in the peritoneal fluid. Cytokine levels were additionally evaluated in the brainstem. RESULTS: SP6 MA and indomethacin treatments reduced inflammatory cell infiltration, vascular permeability and MPO activity in the LPS-exposed rats. Pre-treatment with indomethacin and SP6 MA decreased tumor necrosis factor (TNF)-α levels and preserved interleukin (IL)-10 in the peritoneal fluid. Indomethacin also reduced IL-6 in the peritoneal fluid. In the brainstem, indomethacin reduced IL-1ß, IL-6, TNFα and IL-10, whereas SP6 MA reduced only TNFα and IL-6 levels. CONCLUSIONS: This study clearly demonstrates the anti-inflammatory effect of acupuncture, which we believe may involve the activation of anti-inflammatory neural reflexes in the regulation of peritonitis.

Ankle joint mobilization affects postoperative pain through peripheral and central adenosine A1 receptors.

BACKGROUND: 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. OBJECTIVE: The purpose of this study was to investigate the contribution of the adenosinergic system on the antihyperalgesic effect of ankle joint mobilization (AJM). DESIGN: This was a experimental study. METHODS: 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. RESULTS: 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. LIMITATIONS: The results are limited to animal models and cannot be generalized to acute pain in humans. CONCLUSIONS: 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.

Caffeine at Moderate Doses Can Inhibit Acupuncture-Induced Analgesia in a Mouse Model of Postoperative Pain.

BACKGROUND: The use of acupuncture in the treatment of pain conditions has been extensively investigated. However, the influence of dietary ingredients on acupuncture-induced analgesia (AA) remains unexplored. Recently, the role of adenosine receptors in AA has been shown, and caffeine, one of the world's most commonly consumed dietary ingredients, is an antagonist of these receptors. In this study, the postincisional pain model was used to investigate caffeine's influence on AA. METHOD: Mice submitted to plantar incision surgery were treated with acupuncture needling after administration of acute or chronic caffeine. Acupuncture needling was performed using two different types of stimuli, manual acupuncture and electroacupuncture bilaterally in the acupoint SP6. RESULTS: We found that acute preadministration of caffeine (10 mg/kg, i.p.) completely reversed AA in both types of acupuncture. In the chronic preadministration, we used two doses that mimicked the average daily caffeine consumption in Western countries and China. Interestingly, the Western dose of caffeine (70 mg/kg/day) administered during 8 days in the drinking water reversed AA and the Chinese dose (4 mg/kg/day) administered during the same period did not. CONCLUSIONS: These results indicate that the use of caffeine can inhibit the analgesic effect of different forms of acupuncture. In addition, our findings suggest that doses of caffeine relevant to dietary human intake levels could be a confounding factor in the context of acupuncture research.