Neuropathic pain, defined as the most terrible of all tortures, which a nerve wound may inflict, is a common chronic painful condition caused by gradual damage or dysfunction of the somatosensory nervous system. As with many chronic diseases, neuropathic pain has a profound economic and emotional impact worldwide and represents a major public health issue from a treatment standpoint. This condition involves multiple sensory symptoms including impaired transmission and perception of noxious stimuli, burning, shooting, spontaneous pain, mechanical or thermal allodynia and hyperalgesia.
View Article and Find Full Text PDFNociplastic pain, characterized by abnormal pain processing without an identifiable organic cause, affects a significant portion of the global population. Unfortunately, current pharmacological treatments for this condition often prove ineffective, prompting the need to explore new potential targets for inducing analgesic effects in patients with nociplastic pain. In this context, toll-like receptors (TLRs), known for their role in the immune response to infections, represent promising opportunities for pharmacological intervention because they play a relevant role in both the development and maintenance of pain.
View Article and Find Full Text PDFTraumatic brain injury (TBI) represents one of the leading causes of disability and death worldwide. The annual economic impact of TBI-including direct and indirect costs-is high, particularly impacting low- and middle-income countries. Despite extensive research, a comprehensive understanding of the primary and secondary TBI pathophysiology, followed by the development of promising therapeutic approaches, remains limited.
View Article and Find Full Text PDFChronic stress induces a group of unrecognized cardiovascular impairments, including elevated hemodynamic variables and vascular dysfunction. Moreover, hydrogen sulfide (H 2 S), a gasotransmitter that regulates the cardiovascular system decreases under chronic stress. Thus, this study assessed the impact of sodium hydrosulfide (NaHS) (H 2 S donor) on chronic restraint stress (CRS)-induced cardiovascular changes.
View Article and Find Full Text PDFHydrogen sulfide (HS) is a gasotransmitter implied in metabolic diseases, insulin resistance, obesity, and type 2 Diabetes Mellitus. This study aimed to determine the effect of chronic administration of sodium hydrosulfide (NaHS; inorganic HS donor), L-Cysteine (L-Cys; substrate of HS producing enzymes) and DL-Propargylglycine (DL-PAG; cystathionine-gamma-lyase inhibitor) on the vascular dysfunction induced by insulin resistance in rat thoracic aorta. For this purpose, 72 animals were divided into two main sets that received: 1) tap water (control group; n = 12); and 2) fructose 15% w/v in drinking water [insulin resistance group (IR); n = 60] for 20 weeks.
View Article and Find Full Text PDFHyperglycemia (HG) impairs the renin-angiotensin system (RAS), which may contribute to vascular dysfunction. Besides, hydrogen sulfide (HS) exerts beneficial cardiovascular effects in metabolic diseases. Therefore, our study aimed to determine the effects of chronic administration of sodium hydrosulfide (NaHS; inorganic HS donor) and DL-Propargylglycine [DL-PAG; cystathionine-ץ-lyase (CSE) inhibitor] on the RAS-mediated vascular responses impairments observed in thoracic aortas from male diabetic Wistar rats.
View Article and Find Full Text PDFHydrogen sulfide (HS) is a unique signaling molecule that, along with carbon monoxide and nitric oxide, belongs to the gasotransmitters family. HS is endogenously synthesized by enzymatic and non-enzymatic pathways. Three enzymatic pathways involving cystathionine-γ-lyase, cystathionine-β-synthetase, and 3-mercaptopyruvate sulfurtransferase are known as endogenous sources of HS.
View Article and Find Full Text PDFLife Sci
January 2023
Aim: To assess the effects of subchronic administration with NaHS, an exogenous HS donor, on TBI-induced hypertension and vascular impairments.
Main Methods: Animals underweministration does not prevent the body weight loss but slightly imnt a lateral fluid percussion injury, and the hemodynamic variables were measured in vivo by plethysmograph method. The vascular function in vitro, the ROS levels by the DCFH-DA method and the expression of HS-synthesizing enzymes and eNOS by Western blot were measured in isolated thoracic aortas at day 7 post-TBI.
The systemic cardiovascular effects of major trauma, especially neurotrauma, contribute to death and permanent disability in trauma patients and treatments are needed to improve outcomes. In some trauma patients, dysfunction of the autonomic nervous system produces a state of adrenergic overstimulation, causing either a sustained elevation in catecholamines (sympathetic storm) or oscillating bursts of paroxysmal sympathetic hyperactivity. Trauma can also activate innate immune responses that release cytokines and damage-associated molecular patterns into the circulation.
View Article and Find Full Text PDFThis study aimed to determine if orally administered cannabidiol (CBD) lessens the cortical over-release of glutamate induced by a severe traumatic brain injury (TBI) and facilitates functional recovery. The short-term experiment focused on identifying the optimal oral pretreatment of CBD. Male Wistar rats were pretreated with oral administration of CBD (50, 100, or 200 mg/kg) daily for 7 days.
View Article and Find Full Text PDFHydrogen sulfide (HS) is a gasotransmitter that modulates the peripheral transmission regulating the vascular tone. In vitro studies have suggested that HS induces vasodilation by stimulating capsaicin-sensitive sensory neurons. This study was designed to determine the effects of HS on the non-adrenergic/non-cholinergic (NANC) outflow in the pithed rat, and the underlying mechanisms.
View Article and Find Full Text PDFHydrogen sulfide (HS) is a gasotransmitter that modulates neurotransmission. Indeed, it has been recently demonstrated that HS inhibits the sympathetic outflow in male rats, although the mechanisms remain elusive. Thus, this study evaluated the role of potassium channels on NaHS-induced sympathoinhibition.
View Article and Find Full Text PDFHydrogen sulfide (HS) is a gasotransmitter endogenously synthesized by cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopiruvate sulfurtransferase (3-MST) enzymes. HS exogenous administration prevents the development of hemodynamic impairments after traumatic brain injury (TBI). Since the hypothalamus and the brainstem highly regulate the cardiovascular system, this study aimed to evaluate the effect of NaHS subchronic treatment on the changes of HS-sythesizing enzymes in those brain areas after TBI and in physiological conditions.
View Article and Find Full Text PDFThe dense network of capillaries composed of capillary endothelial cells (cECs) and pericytes lies in close proximity to all neurons, ideally positioning it to sense neuron- and glial-derived compounds that enhance regional and global cerebral perfusion. The membrane potential () of vascular cells serves as the physiological bridge that translates brain activity into vascular function. In other beds, the ATP-sensitive K (K) channel regulates in vascular smooth muscle, which is absent in the capillary network.
View Article and Find Full Text PDFTraumatic brain injury (TBI) represents a critical public health problem around the world. To date, there are no accurate therapeutic approaches for the management of cardiovascular impairments induce by TBI. In this regard, hydrogen sulfide (HS), a novel gasotransmitter, has been proposed as a neuro- and cardioprotective molecule.
View Article and Find Full Text PDFHydrogen sulfide plays an important role in the regulation of the cardiovascular system, insulin secretion, and glucose homeostasis. The aim of the present study was to examine the effects of chronic treatment with sodium hydrosulfide (NaHS), L-Cysteine (L-Cys) and DL-Propargylglycine (DL-PAG) on the changes induced by a high-fat diet (HFD) in zoometric and metabolic variables as well as cardiovascular changes such as hypertension and sympathetic hyperactivity. For this purpose, male Wistar rats were fed a normal fat diet (NFD) or HFD for 12 weeks.
View Article and Find Full Text PDFHydrogen sulfide is a gasotransmitter that mediates cardiovascular responses and could protect the heart from ischemia-reperfusion damage. Furthermore, this gas mediates bradycardia although the mechanisms involved remain elusive. In this regard, the inhibition of the cardiac sympathetic outflow may be partially involved.
View Article and Find Full Text PDFIt has been reported that metformin reduces blood pressure although the mechanisms have not been described. Indeed, several mechanisms could be implicated including the interaction with α-adrenoceptors or inhibition of sympathetic outflow. Therefore, this study was designed to determine the capability of metformin to block the vasopressor responses induced by α-adrenoceptor agonists or selective electrical stimulation of sympathetic outflow.
View Article and Find Full Text PDFIt has been reported that i.v. administration of NaHS, a donor of H2S, elicited dose-dependent hypotension although the mechanisms are not completely understood.
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