Collaborative action between noradrenergic and serotoninergic systems in peripheral antinociception in mice.

Noradrenaline (NA) and serotonin (5-HT) induce nociception and antinociception. This antagonistic effect can be explained by the dose and type of activated receptors. We investigated the existence of synergism between the noradrenergic and serotonergic systems during peripheral antinociception.

Participation of the cannabinoid system and the NO/cGMP/K pathway in serotonin-induced peripheral antinociception.

It has already been shown that serotonin can release endocannabinoids at the spinal cord level, culminating in inhibition of the dorsal horn. At the peripheral level, cannabinoid receptors modulate primary afferent neurons by inhibiting calcium conductance and increasing potassium conductance. Studies have shown that after the activation of opioid receptors and cannabinoids, there is also the activation of the NO/cGMP/K pathway, inducing cellular hyperpolarization.

Anandamide reduces the migration of lymphocytes to the intestine by CB2 activation and reduces TNF-α in the target organs, protecting mice from graft-versus-host disease.

Graft-versus-host disease (GVHD) is a serious inflammatory illness that often occurs as a secondary complication of bone marrow transplantation. Current therapies have limited effectiveness and fail to achieve a balance between inflammation and the graft-versus-tumor effect. In this study, we investigate the effects of the endocannabinoid anandamide on the complex pathology of GVHD.

COX/iNOS dependence for angiotensin-II-induced endothelial dysfunction.

Vascular dysfunction induced by angiotensin-II can result from direct effects on vascular and inflammatory cells and indirect hemodynamic effects. Using isolated and functional cultured aortas, we aimed to identify the effects of angiotensin-II on cyclooxygenase (COX) and inducible nitric oxide synthase (iNOS) and evaluate their impact on vascular reactivity. Aortic rings from mice were incubated overnight in culture medium containing angiotensin-II (100 nmol/L) or vehicle to induce vascular disfunction.

Involvement of the cannabinoid system in chronic inflammatory intestinal diseases: opportunities for new therapies.

The components of the endogenous cannabinoid system are widely expressed in the gastrointestinal tract contributing to local homeostasis. In general, cannabinoids exert inhibitory actions in the gastrointestinal tract, inducing anti-inflammatory, antiemetic, antisecretory, and antiproliferative effects. Therefore, cannabinoids are interesting pharmacological compounds for the treatment of several acute intestinal disorders, such as dysmotility, emesis, and abdominal pain.

Cannabidiol Enhances Intestinal Cannabinoid Receptor Type 2 Receptor Expression and Activation Increasing Regulatory T Cells and Reduces Murine Acute Graft-versus-Host Disease without Interfering with the Graft-versus-Leukemia Response.

Cannabidiol (CBD) is a highly lipidic phytocannabinoid with remarkable anti-inflammatory effects. The aim of this study was to evaluate CBD's effects and mechanisms of action in the treatment of mice subjected to acute graft-versus-host disease (aGVHD). aGVHD was induced by the transplantation of bone marrow cells and splenocytes from C57BL-6j to Balb-c mice.

α-Adrenoceptor agonist induces peripheral antinociception via the endocannabinoid system.

Background: Xylazine is an α adrenoceptor agonist that is extensively used in veterinary medicine and animal experimentation procedures to produce analgesia, sedation and muscle relaxation without causing general anesthesia. Considering the lack of knowledge of the mechanisms involved in peripheral antinociception induced by xylazine and the potential interactions between the adrenergic and endocannabinoid systems, the present study investigated the contribution of the latter system in the mechanism of xylazine.

Methods: The rat paw pressure test, in which hyperalgesia was induced by the intraplantar injection of prostaglandin E, was performed.

Evidence for the involvement of opioid and cannabinoid systems in the peripheral antinociception mediated by resveratrol.

Despite all the development of modern medicine, around 100 compounds derived from natural products were undergoing clinical trials only at the end of 2013. Among these natural substances in clinical trials, we found the resveratrol (RES), a pharmacological multi-target drug. RES analgesic properties have been demonstrated, although the bases of these mechanisms have not been fully elucidated.

Noradrenaline induces peripheral antinociception by endogenous opioid release.

Background: The aim of this study was to investigate this involvement in not inflammatory model of pain and which opioid receptor subtype mediates noradrenaline-induced peripheral antinociception. Noradrenaline is involved in the intrinsic control of pain-inducing pro-nociceptive effects in the primary afferent nociceptors. However, inflammation can induce various plastic changes in the central and peripheral noradrenergic system that, upon interaction with the immune system, may contribute, in part, to peripheral antinociception.

Serotonin induces peripheral antinociception via the opioidergic system.

Purpose: Studies conducted since 1969 have shown that the release of serotonin (5-HT) in the dorsal horn of the spinal cord contributes to opioid analgesia. In the present study, the participation of the opioidergic system in antinociceptive effect serotonin at the peripheral level was examined.

Methods: The paw pressure test was used with mice (Swiss, males from 35 g) which had increased pain sensitivity by intraplantar injection of PGE (2 μg).

Inhibition of 5-lipoxygenase alleviates graft-versus-host disease.

Leukotriene B (LTB), a proinflammatory mediator produced by the enzyme 5-lipoxygenase (5-LO), is associated with the development of many inflammatory diseases. In this study, we evaluated the participation of the 5-LO/LTB axis in graft-versus-host disease (GVHD) pathogenesis by transplanting 5-LO-deficient leukocytes and investigated the effect of pharmacologic 5-LO inhibition by zileuton and LTB inhibition by CP-105,696. Mice that received allogeneic transplant showed an increase in nuclear 5-LO expression in splenocytes, indicating enzyme activation after GVHD.

κ-Opioid receptor participates of NSAIDs peripheral antinociception.

NSAIDs represent some of the most widely prescribed drugs for relief of short-term fever, pain and inflammation. The participation of the opioid system in the peripheral is poorly understood. The aim of this study was evaluate the role of opioid system in the peripheral antinociception by diclofenac and dipyrone.

Natural Diterpenes from Coffee, Cafestol, and Kahweol Induce Peripheral Antinoceception by Adrenergic System Interaction.

Cafestol and kahweol are diterpenes found only in the non-saponified lipid fraction of coffee. They are released during boiling and retained in the filtration process. Previous studies have shown peripheral antinociception induced by endogenous opioid peptides released by these diterpenes.

NSAIDs induce peripheral antinociception by interaction with the adrenergic system.

Aims: We evaluated the role of adrenergic systems on the peripheral antinociception induced by dipyrone and diclofenac. Mainmethods: The rat pawpressure test, inwhich sensitivity is increased by intraplantar injection of prostaglandin E2, was used to examine the peripheral effects of locally administered drugs.

Key Findings: Dipyrone (10, 20 and 40 μg) and diclofenac (5, 10 and 20 μg) administered locally into the right paw elicited a dose-dependent antinociceptive effect, which was demonstrated to be local; the injection of drugs into the ipsilateral and contralateral hindpaws demonstrated an effect only in the ipsilateral paw because only the treated paw produced an antinociceptive effect.