Role Of Capsaicin-sensitive Nerves Research Articles

The Role of Capsaicin-Sensitive Nerves in Regulating Blood Dehydroepiandrosterone Sulfate Levels in Rats in Normal Conditions and in Metabolic Syndrome

The effects of stimulation of capsaicin-sensitive nerves (CSN, capsaicin 1 mg/kg, s.c.) and their deafferentation (capsaicin 150 mg/kg s.c.) on the blood dehydroepiandrosterone sulfate (DEAS) level in normal conditions and metabolic syndrome (MS) induced by consumption of fructose (12.5% solution, 10 weeks) were studied. The criterion for the development of MS was provided by data showing increased blood triglycerides, lipid peroxidation (LPO) products, and impaired glucose tolerance. Stimulation of CSN in rats with a normal diet led to an increased DEAS level, while deafferentation decreased the blood level of this hormone. The fructose diet decreased the DEAS level, induced triglyceridemia, increased LPO, and impaired glucose tolerance. The decreased blood DEAS concentration seen after consumption of fructose was eliminated by stimulation of CSN, with simultaneous reductions in indicators of metabolic syndrome. Preliminary deafferentation of CSN in fructose-consuming rats blocked the stimulation-induced restoration of DEAS. The authors suggest that CSN are involved in the mechanisms controlling the blood DEAS content in normal conditions and metabolic syndrome.

Role of capsaicin-sensitive nerves and tachykinins in mast cell tryptase-induced inflammation of murine knees.

Mast cell tryptase (MCT) is elevated in arthritic joints, but its direct effects are not known. Here, we investigated MCT-evoked acute inflammatory and nociceptive mechanisms with behavioural, in vivo imaging and immunological techniques. Neurogenic inflammation involving capsaicin-sensitive afferents, transient receptor potential vanilloid 1 receptor (TRPV1), substance P (SP), neurokinin A (NKA) and their NK1 tachykinin receptor were studied using gene-deleted mice compared to C57Bl/6 wildtypes (n=5-8/group). MCT was administered intraarticularly or topically (20μl, 12μg/ml). Capsaicin-sensitive afferents were defunctionalized with the TRPV1 agonist resiniferatoxin (RTX; 30-70-100μg/kgs.c. pretreatment). Knee diameter was measured with a caliper, synovial perfusion with laser Doppler imaging, mechanonociception with aesthesiometry and weight distribution with incapacitance tester over 6h. Cytokines and neuropeptides were determined with immunoassays. MCT induced synovial vasodilatation, oedema, impaired weight distribution and mechanical hyperalgesia, but cytokine or neuropeptide levels were not altered at the 6-h timepoint. Hyperaemia was reduced in RTX-treated and TRPV1-deleted animals, and oedema was absent in NK1-deficient mice. Hyperalgesia was decreased in SP/NKA- and NK1-deficient mice, weight bearing impairment in RTX-pretreated, TRPV1- and NK1-deficient animals. MCT evokes synovial hyperaemia, oedema, hyperalgesia and spontaneous pain. Capsaicin-sensitive afferents and TRPV1 receptors are essential for vasodilatation, while tachykinins mediate oedema and pain.

Role of capsaicin-sensitive nerves and histamine H 1, H 2, and H 3 receptors in the gastroprotective effect of histamine against stress ulcers in rats

It is assumed that an overproduction of gastric acid is the most important factor in the development of peptic ulcer. However, it has been also demonstrated that gastric defense mechanisms, which prevent mucosal injury, are enhanced by the same factors that increase acid secretion. The aim of this study was to examine the role of capsaicin-sensitive sensory nerves and histamine H 1, H 2, and H 3 receptors in histamine-induced gastroprotection against stress ulcers. Studies were performed on rats with intact or ablated sensory nerves. Ablation of sensory nerves was induced by neurotoxic doses of capsaicin. Gastric ulcers were induced by water immersion and restrain stress. Before exposure to stress, rats were pretreated with saline (control), histamine (10 μmol/kg), histamine H 1 receptor antagonist pyrilamine (100 μmol/kg), histamine H 2 receptor antagonist ranitidine (100 μmol/kg), histamine H 3 receptor antagonist thioperamide (100 μmol/kg), or a combination of histamine with these histamine receptor antagonists. Results Histamine alone reduced ulcer area evoked by stress and this effect was accompanied by an increase in gastric mucosal blood flow and mucosal DNA synthesis, as well as a decrease in serum pro-inflammatory interleukin-1β concentration. Treatment with combination of pyrilamine plus histamine caused an increase in gastric ulcer area and serum interleukin-1β above the value observed in animals treated with saline, and this effect was accompanied by a decrease in gastric mucosal DNA synthesis. Ranitidine, in combination with histamine, reduced the ulcer area and serum interleukin-1β to a minimal value, whereas gastric mucosal blood flow and DNA synthesis reached a maximal value. Pretreatment with thioperamide before histamine administration abolished the histamine-evoked reduction in gastric ulcer area. Ablation of sensory nerves increased the ulcer area in animals treated with saline or histamine, or histamine in combination with pyrilamine or ranitidine. In animals with sensory nerves ablation combined with administration of thioperamide plus histamine, the ulcer area was similar to that in saline-treated animals with intact sensory nerves. We conclude that: (1) histamine exhibits protective effect against stress-induced gastric ulcer and that this gastroprotection is related to stimulation of histamine H 1 and H 3 receptors; (2) blockade of histamine H 2 receptors exhibited beneficial effect on gastric mucosa against stress-induced gastric ulcers; and (3) ablation of sensory nerves aggravates stress-induced gastric ulcer and reduces histamine-evoked gastroprotection related to stimulation of histamine H 3 receptors.

Role of capsaicin-sensitive nerves in gastric and hepatic injury induced by cold-restraint stress.

The role of capsaicin-sensitive afferent fibers on cold-restraint stress-induced gastric and hepatic injury was examined at the macroscopic and ultrastructural levels. Wistar albino rats were treated with capsaicin either locally (intragastric, perivagal, and periceliac) or systemically (neonatal, intraperitoneal). Perineural and neonatal treatment with capsaicin was used to denervate afferent fibers, while intragastric capsaicin treatment would have activated mucosal afferent fibers just before the stress exposure. Capsaicin decreased significantly the formation of macroscopic gastric lesions caused by stress in all treatment groups. At the electron microscopic level, however, denervation of vagal afferent fibers with capsaicin was most effective in prevention of cellular injury in gastric mucosa. In the liver, systemic denervation of afferent fibers completely inhibited stress-induced cellular damage, while denervation of afferent fibers in vagus and splanchnic nerve was partially effective. Central neural pathways sensitive to capsaicin may mediate formation of both gastric and hepatic injury resulting from stress.

Role of capsaicin sensitive nerves in epidermal growth factor effects on gastric mucosal injury and blood flow

Background—Epidermal growth factor (EGF) and capsaicin protect against experimental gastric mucosal injury. Capsaicin exerts its gastroprotective effect by stimulating afferent neurones leading to release of calcitonin gene related peptide (CGRP)...

Stress ulceration: Role of capsaicin-sensitive nerves in rat model: [formula omitted], H Ojeas, M Kida, K Brewer, J Gao, T Hoag and R Harty. Department of Medicine, University of Oklahoma and Oklahoma City DVAMC, Oklahoma City, OK

Stress ulceration: Role of capsaicin-sensitive nerves in rat model: [formula omitted], H Ojeas, M Kida, K Brewer, J Gao, T Hoag and R Harty. Department of Medicine, University of Oklahoma and Oklahoma City DVAMC, Oklahoma City, OK

Airways hyperreactivity and cellular accumulation in a delayed-type hypersensitivity reaction in the mouse. Modulation by capsaicin-sensitive nerves.

The aim of this study was to investigate the possible role of capsaicin-sensitive nerves in a pulmonary delayed-type hypersensitivity (DTH) reaction. Mice (Balb/c) were skin-sensitized with dinitrofluorobenzene (DNFB; 0.5%, 100 microliters) on two consecutive days and challenged intranasally 5 days later with dinitrobenzene sulphonic acid (0.6%, 50 microliters). Sensitized mice exhibited tracheal hyperreactivity to carbachol 24 and 48 h after challenge; however, no hyperreactivity was observed 2 h after challenge. At 24 h, but not at 48 h, hyperreactivity was associated with antigen-specific lymphocyte accumulation in bronchoalveolar lavage fluid (BALF). Capsaicin pretreatment, resulting in the depletion of sensory neuropeptides, virtually abolished hyperreactivity to carbachol 24 and 48 h after challenge in sensitized mice. Although at 24 h after challenge the lymphocyte population was elevated in the BALF collected from capsaicin-pretreated mice, this accumulation was not antigen-specific. Additionally, there was an increase in polymorphonuclear leukocyte accumulation (neutrophils and eosinophils) in the BALF collected from capsaicin-pretreated mice at this time point, but this increase was more profound in the sensitized group. In summary, tracheal hyperreactivity and cellular accumulation are prominent features of the lymphocyte-associated DTH reaction induced by DNFB in the mouse lung. Evidence presented in this report highlights the possible importance of sensory neuropeptides in pulmonary inflammation and airways hyperreactivity.

O-266 - Role of capsaicin-sensitive nerves in post-tetanic hyperemia in rat femoral artery.

O-266 - Role of capsaicin-sensitive nerves in post-tetanic hyperemia in rat femoral artery.

Role of capsaicin-sensitive nerves in airway hyperresponsiveness induced by platelet activating factor in the rabbit

A new hypothesis for the pathophysiological mechanism underlying the development of oedema after a thermal injury has been tested in an experimental burn model. Support was given to the suggestion that oxygen-derived free radicals produced by invading leucocytes which upon activation release the superoxide radical (O2−), may be partly responsible for the increase in microvascular permeability seen after thermal injury. By removal of oxygen-derived free radicals with radical scavengers (superoxide dismutase and catalases) it was possible to reduce significantly the post-burn oedema formation. For comparison, one series of rats was pretreated with hydrocortisone and another with the histamine H2-blocker cimetidine. Hydrocortisone reduced the very early post-burn oedema formation which might partly be due to its membrane-stabilizing influence and partly to a direct effect on the microvasculature, causing a reduction of the vasodilatation observed post-burn. The inhibition of post-burn oedema formation by cimetidine, earlier demonstrated in animal burn models, was confirmed in the present study. The mean arterial blood pressure (MAP) in the cimetidine-treated rats decreased, however, after treatment. It is therefore difficult to determine to what extent the concentration of oedema is attributable to histamine H2-receptor blockade and to what extent to the reduced blood pressure. The influence of MAP on post-burn oedema formation was further illustrated in two series of rats anaesthetized with Inactin and Hypnorm/Valium respectively. The results underline the importance of using the same anaesthetic throughout the experimental series.

Ion Transport in Rat Tracheal EpitheliumIn Vitro: Role of Capsaicin-sensitive Nerves in Allergic Reactions

Tracheas from control rats or rats sensitized to egg albumin (EA) were studied in vitro in Ussing chambers, and changes in short-circuit current (Isc) induced by the addition of antigen or agonists on the mucosal (luminal) side were recorded. Addition of EA (100 micrograms/ml) to tracheas from sensitized but not from control rats caused a slow increase of Isc beginning after 15 to 30 s and maximal at 3 to 4 min. This response was inhibited in the presence of doxantrazole, a mucosal mast-cell-stabilizing agent, but not by sodium cromoglycate. A separate group of rats was treated neonatally with capsaicin to deplete peptide neurotransmitters. Responses to EA were significantly lower in capsaicin-treated, sensitized rats than in untreated, sensitized control littermates. No difference was seen in the level of serum EA-specific IgE in these two groups. In tracheas from untreated rats, addition of substance P, capsaicin, platelet-activating factor, and acetylcholine caused an immediate and marked increase in Isc. Responses to substance P and acetylcholine were unaffected by capsaicin treatment. However, responses to capsaicin itself and also to PAF were reduced. These data indicate that changes of net ion transport across the airway epithelium are early phenomena of local hypersensitivity reactions, and that neurotransmitters such as substance P may play an important role in the control of these phenomena.