Carvacrol is a phenolic monoterpene present in the essential oil of the family Lamiaceae, as in the genera Origanum and Thymus. We previously reported that carvacrol is effective as an analgesic compound in various nociceptive models, probably by inhibition of peripheral mediators that could be related with its strong antioxidant effect observed in vitro. In this study, the anti-hypernociceptive activity of carvacrol was tested in mice through models of mechanical hypernociception induced by carrageenan, and the involvement of important mediators of its signaling cascade, as tumor necrosis factor-alpha (TNF-α), prostaglandin E(2) (PGE(2)), and dopamine, were assessed. We also investigated the anti-inflammatory effect of carvacrol on the model of carrageenan-induced pleurisy and mouse paw edema, and the lipopolysaccharide (LPS)-induced nitrite production in murine macrophages was observed. Systemic pretreatment with carvacrol (50 or 100 mg/kg; i.p.) inhibited the development of mechanical hypernociception and edema induced by carrageenan and TNF-α; however, no effect was observed on hypernociception induced by PGE(2) and dopamine. Besides this, carvacrol significantly decreased TNF-α levels in pleural lavage and suppressed the recruitment of leukocytes without altering the morphological profile of these cells. Carvacrol (1, 10, and 100 μg/mL) also significantly reduced (p < 0.001) the LPS-induced nitrite production in vitro and did not produce citotoxicity in the murine peritoneal macrophages in vitro. The spontaneous locomotor activity of mice was not affected by carvacrol. This study adds information about the beneficial effects of carvacrol on mechanical hypernociception and inflammation. It also indicates that this monoterpene might be potentially interesting in the development of novel tools for management and/or treatment of painful conditions, including those related to inflammatory and prooxidant states.

Background and purpose: Recent findings suggest that the noxious gas H2S is produced endogenously, and that physiological concentrations of H2S are able to modulate pain and inflammation in rodents. This study was undertaken to evaluate the ability of endogenous and exogenous H2S to modulate carrageenan-induced synovitis in the rat knee. Experimental approach: Synovitis was induced in Wistar rats by intra-articular injection of carrageenan into the knee joint. Sixty minutes prior to carrageenan injection, the rats were pretreated with indomethacin, an inhibitor of H2S formation (DL-propargylglycine) or an H2S donor [Lawesson's reagent (LR)]. Key results: Injection of carrageenan evoked knee inflammation, pain as characterized by impaired gait, secondary tactile allodynia of the ipsilateral hindpaw, joint swelling, histological changes, inflammatory cell infiltration, increased synovial myeloperoxidase, protein nitrotyrosine residues, inducible NOS (iNOS) activity and NO production. Pretreatment with LR or indomethacin significantly attenuated the pain responses, and all the inflammatory and biochemical changes, except for the increased iNOS activity, NO production and 3-NT. Propargylglycine pretreatment potentiated synovial iNOS activity (and NO production), and enhanced macrophage infiltration, but had no effect on other inflammatory parameters. Conclusions and implications:Whereas exogenous H2S delivered to the knee joint can produce a significant antiinflammatory and anti-nociceptive effect, locally produced H2S exerts little immunomodulatory effect. These data further support the development and use of H2S donors as potential alternatives (or complementary therapies) to the available anti-inflammatory compounds used for treatment of joint inflammation or relief of its symptoms.

Physical exercise reduces the deleterious effects of cardiovascular and inflammatory disorders. The purpose of the present study was to evaluate the beneficial effects of physical training on the inflammatory responses following lung ischaemia-reperfusion (IR) in rats.Male Wistar rats were divided into sham-operated animals and sedentary and trained animals submitted to lung IR. The run training programme consisted of 5 sessions?week , at 66% of maximal oxygen consumption for 8 weeks. The left pulmonary artery, bronchus and pulmonary vein were occluded for 90 min and reperfused for 2 h. Lung protein extravasation was measured as 125 I-human albumin accumulation, whereas lung neutrophil infiltration was measured as myeloperoxidase activity. Lung IR in sedentary rats resulted in marked increases in protein extravasation and neutrophil influx, and in significant elevations of serum tumour necrosis factor (TNF)-a and interleukin (IL)-1b levels. Physical preconditioning attenuated the increased IR-induced protein leakage without affecting neutrophil influx. It also reduced serum TNF-a (and IL-1b) levels, but had no effect on IL-10 levels. Plasma superoxide dismutase activity was significantly increased in trained IR rats.The present data show that physical preconditioning protects the rat lung from ischaemiareperfusion injury by attenuating the pulmonary vascular permeability that may be a consequence of reduced levels of tumour necrosis factor-a and interleukin-1b and elevated superoxide dismutase activity.

The aim of this study was to evaluate the effectiveness of pre-exercise low-level phototherapy (Light-Emitting Diode therapy [LEDtherapy] or Light Amplification by Stimulate Emission of Radiation therapy [LASERtherapy]) in increasing exercise capacity and muscle performance of people undergoing exercise when compared to placebo treatment. Randomized controlled trials and crossover studies were sought on CENTRAL, MEDLINE, EMBASE, SciELO, PEDro and LILACS from its inception up to February 2015. References lists of included studies were sought for additional relevant research. Two authors independently extracted data on study design, treatment parameters, exercise capacity (number of repetitions, time to exhaustion, blood lactate concentration and lactate dehydrogenase activity) and muscle performance (torque, power and strength) using an structured table. Agreement should be reached by consensus or by a third reviewer. Sixteen studies involving 297 participants were included. Improvement of number of repetitions (mean difference [MD] [95 % confidence interval] = 3.51 repetitions [0.65-6.37]; P = 0.02), delay in time to exhaustion (MD = 4.01 s [2.10-5.91]; P < 0.0001), reduction in lactate levels (MD = 0.34 mmol/L [0.19-0.48]; P < 0.00001) and increased peak torque (MD = 21.51 Nm [10.01-33.01]; P < 0.00001) were observed when LASERtherapy was applied. LEDtherapy meta-analyses were performed with two studies and retrieved no between-group statistically significant difference in power, lactate levels or time to exhaustion. Although our results suggest that LASERtherapy is effective in improving skeletal muscle exercise capacity, the quality of the current evidence is limited.