Cannabinoid and Serotonergic Systems: Unraveling the Pathogenetic Mechanisms of Stress-Induced Analgesia.

The perception of "stress" triggers many physiological and behavioral responses, collectively called the stress response. Such a complex process allows for coping with stress and also triggers severe pathology. Because of the multidirectional effect of stress on the body, multiple systems participate in its pathogenesis, with the endogenous cannabinoid and the serotoninergic ones among them. These two systems also take part in the pain perception decrease, known as stress-induced analgesia (SIA), which can then be taken as an indirect indicator of the stress response. The aim of our study was to study the changes in cold SIA (c-SIA) resulting from the exogenous activation of cannabinoid receptor type 1 (CB1) and 5-hydroxytryptamine (5-HT, serotonin) receptor type 1A (5-HT1A). Various combinations of agonists and/or antagonists of CB1 and 5-HT1A, before or after 1 h of cold exposure, were applied, since we presumed that the exogenous activation of the receptors before the cold exposure would influence the pathogenesis of the stress response, while their activation after the stressful trigger would influence the later development. Our results show that the serotonergic system "maintained" c-SIA in the pre-stress treatment, while the cannabinoids' modulative effect was more prominent in the post-stress treatment. Here, we show the interactions of the two systems in the stress response. The interpretation and understanding of the mechanisms of interaction between CB1 and 5-HT1A may provide information for the prevention and control of adverse stress effects, as well as suggest interesting directions for the development of targeted interventions for the control of specific body responses.

Circulating Asprosin Concentrations in Patients with Obesity and Carbohydrate Disturbances.

Asprosin is a fasting-induced glucogenic hormone, secreted by white adipose tissue in response to starvation. The aim of the current study was to determine the levels of asprosin in subjects from the entire spectrum of the carbohydrate metabolism. A total of 153 Causcasian subjects participated in this study: group 1, healthy volunteers; group 2, obese subjects without glycemic disturbances; group 3, subjects with prediabetes and group 4, patients with newly identified type 2 diabetes. Subject with body mass index≥30 kg/m2 and dysglycemia (prediabetes and diabetes) showed significantly high levels of asprosin (1.40 ng/ml [IQR=0.98-1.94]; 1.27 ng/ml [IQR=0.86-2.12]; 1.09 ng/ml [IQR=0.89-1.58]) compared to the control group (0.71 ng/ml [IQR=0.54-0.92]; p<0.001). Correlation analysis showed that serum asprosin also had significant positive associations with some anthropometric parameters, liver enzymes, fasting and post load glucose and insulin, LDL and triglycerides. Furthermore, we estimated a marked relationship between asprosin concentrations and intima media thickness of the common carotid artery as well as neuropathy disability and vibration sensitivity. The circulating asprosin levels for differentiating subjects with carbohydrate disturbances and those with obesity were determined by ROC analysis. The AUC for disturbances of the glucose metabolism was 0.672 (p<0.001; 95% CI=0.581-0.751) and for obesity AUC was 0.849 (p<0.001; 95% CI=0.785-0.919). Circulating asprosin could be used as a predictive factor for early carbohydrate disorders and might be a potential new therapeutic target for the treatment of dysglycemia and obesity. Further prospective studies are needed to confirm this observation.

Microvascular reactivity during sympathetic stimulations in Raynaud's phenomenon.

BACKGROUND: The objective of the study was to assess skin autonomic microvascular reactivity to sympathetic stimulations and its association with primary and secondary Raynaud's phenomenon (RP). METHODS: Laser-Doppler recorded finger pulp skin blood flow was monitored during orthostatic and deep breathing tests of 4 subjects groups, each of them composed of 20 subjects: group 1, healthy controls; group 2, vibration-induced secondary RP (vRP); group 3, primary RP (pRP); group 4, systemic sclerosis-related secondary RP (sclRP). Within groups comparisons by Wilcoxon matched pairs rank test and between groups by Bonferroni's multiple test for unpaired data were done using SPSS Statistics software. RESULTS: Reliably lower initial perfusion values were established in all the RP patients. The local sympathetic axon-reflex mediated responses to orthostasis were reduced in all RP groups with increased perfusions in upright posture instead of decreased. The vasoconstrictor responses to deep breathing tended to increase instead of decreasing in the vRP and pRP groups, while in the sclRP group the perfusions decreased. Strong correlations between the initial finger pulp perfusions and the orthostatic and deep breathing perfusion responses were found in the control, pRP and vRP groups (P<0.0001) and a modest correlation between the initial perfusions and the deep breathing perfusion responses in the sclRP group. CONCLUSIONS: Abnormal cutaneous microvascular reactivity to central and local axon-reflex sympathetic stimulations was established in RP patients reflecting self-regulatory dysfunctions which might contribute to the manifestations of the ischemic microcirculatory paroxysms. Laser Doppler flowmetry with functional orthostatic and deep breathing tests contribute to the diagnosis of RP.