Histamine Stimuli Research Articles

Nocebo Effects and Scratching Behaviour on Itch.

Nocebo effects, i.e. reduced treatment effects due to patients' negative expectations, play a role in itch. Recent studies have shown that nocebo effects can be induced experimentally on itch and also be minimized and even turned into the opposite direction, i.e. placebo effects. It is not known whether these effects generalize to itch-associated scratching behaviour. The aim of this study was to determine whether induction and reversal of nocebo effects on itch evoked by electrical and histamine stimuli generalized to scratching. Ninety-seven healthy participants were included in the study. The manipulation was successful, as during the nocebo learning phase, increased scratching responses were found for higher intensity compared with lower intensity itch stimuli. During the testing phase of induction or reversal of the nocebo effects, however, no significant nocebo effects or reversed nocebo effects, were found in scratching. Thus, no straightforward generalization of nocebo effects from itch to scratching was found in this laboratory setting. Further investigation into possible generalization is needed in different settings and in patients with chronic itch.

Prostaglandin D2 Modulates Neuronal Excitation of the Trigeminal Ganglion to Augment Allergic Rhinitis in Guinea Pigs.

Prostaglandin D2(PGD2) is involved in the pathogenesis of allergic rhinitis. However, the sensory nervous system-mediated contributions of PGD2to the symptoms of allergic rhinitis remain unclear. We investigated the involvement of PGD2in these symptoms and in neuronal excitation by in vivo and ex vivo experiments. In an ovalbumin-induced model of allergic rhinitis in guinea pigs, the number of sneezing, nasal rubbing, and nasal secretion events were assessed after the nasal cavity instillation of PGD2, histamine, or a combination of PGD2and histamine. In situ hybridization for PGD2receptor 1 (DP1) mRNA transcripts and immunohistochemical analysis of histamine H1receptor protein expression in guinea pig trigeminal ganglion (TRG) were performed. The effects of DP1receptor activation on the excitability of TRG neurons to electrical and histamine stimuli were assessed using whole-cell patch-clamp recordings. Histamine induced more sneezing, nasal rubbing, and nasal secretion events than PGD2 PGD2augmented histamine-induced responses, whereas pretreatment with a DP1receptor-selective antagonist completely suppressed PGD2-induced augmentation. DP1receptor mRNA transcripts and H1receptor protein expression could be detected in TRG neurons. Moreover, a DP1receptor agonist caused significant increases in the number of histamine-induced action potentials and depolarization, and reduced the current threshold in small-diameter neurons. Our findings show that PGD2-DP1receptor signaling augments the symptoms of allergic rhinitis via the sensory nervous system by modulating nasal neuronal activation to various stimuli, such as histamine. These findings suggest that DP1receptor antagonist has therapeutic potential for the treatment of allergic rhinitis.

α-Tocopherol Improves Microcirculatory Dysfunction on Fructose Fed Hamsters.

Fructose, an everyday component of western diet associated to chronic hyperglycemia and enhanced free radical production, impairs endothelial function and supplementation with antioxidants might improve it. In this study we investigated if vitamin E could reverse the microvascular damage elicited by fructose. Male Syrian golden hamsters drank either 10% fructose solution (F) or filtered water (C), combined with three concentrations of vitamin E in their chows [zero, normal (VE) or 5X (5XVE)] during 60 days. Microvascular reactivity in response to topical application of acetylcholine (Ach; endothelium-dependent vasodilator) or sodium nitroprusside (SNP; endothelium-independent vasodilator) and macromolecular permeability increase induced by either 30 min ischemia followed by reperfusion (I/R) or topical application of histamine (5 μM) were assessed using the cheek pouch preparation. Compared to controls (drinking filtered water), fructose-drinking animals showed decreased vasodilatation to acetylcholine in all concentrations tested (-56.2% for 10-9M, -53.9% for 10-7M and -43.7% for 10-5M). On the other hand, vitamin E supplementation resulted in increased responses for both water and fructose drinking groups (177.4% for F vs. F/5XVE and 241.6% for C vs. C/5XVE for 10-5M Ach). Endothelial-independent vasodilatation explored by topical application of SNP was restored and even enhanced with the supplementation of 5X vitamin E in both groups (80.1% for F vs. F/5XVE; 144.2% for C vs. C/5XVE; 3.4% of difference for C/5XVE vs. F/5XVE on 10-5M SNP). The number of leaky sites after I/R and histamine stimuli in vitamin E supplemented animals decreased (-25.1% and -15.3% for F vs. F/5XVE; and -21.7% and -16% of leaky sites comparing C vs. C/5XVE, respectively for I/R and histamine stimuli) pointing to tightening of the endothelial barrier for macromolecular permeability. Our results strongly suggest that vitamin E could improve the endothelial function and permeability barrier and also reverse impairments elicited by sugar overload.

Activation of Type 1 Cannabinoid Receptor (CB1R) Promotes Neurogenesis in Murine Subventricular Zone Cell Cultures

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+]i) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.

Responses to Methacholine, Histamine and Osmotic Stimuli after Treatment with Interleukin-13 or Propranolol in Balb/c Versus CFW Mice

Responses to Methacholine, Histamine and Osmotic Stimuli after Treatment with Interleukin-13 or Propranolol in Balb/c Versus CFW Mice

Neuronal sensitization for itch in patients with chronic pruritus

Itch is one of the major symptoms of various skin diseases. Although specific neuronal pathways for itch were identified both peripherally and centrally, they still fail to explain itchy skin observed in patients with chronic pruritus. In this study, sensitivity to itchy and painful stimuli in patients with atopic dermatitis was investigated. Histamine‐prick evoked enormous itch in their lesional skin, while less itch in their non‐lesional skin than healthy subjects. Flare reaction was not significantly different between their non‐lesional and lesional skin, rather smaller than healthy subjects. Mechanical (pin‐pricks), electrical, heat and chemical (injection of pH3 solution) stimuli evoked intense itch in their lesional skin and partly also in their non‐lesional skin, while only pain in healthy subjects. Itch was also, but not intensely, evoked in healthy subjects by injection of pH3 solution after sufficient histamine stimuli. These results confirm the presence of itchy skin with hyperkinesis (excessive itch by itchy stimuli) and allokinesis (itch by non‐itchy stimuli) in patients with atopic dermatitis, which is so intense that painful stimuli cannot suppress but evoke itch, and suggest that neuronal sensitization is involved in their itch not only peripherally but also centrally.

Imaging of central itch modulation in the human brain using positron emission tomography

The unpleasantness of itching is reduced by cooling. Although previous research suggests the presence of a central itch modulation system, there is little documentation about the modulation system in the brain. In the present study, we investigated the modulating system of the itching sensation in human brains using positron emission tomography and H 2 15O. The significant increases of regional cerebral blood flow caused by histamine stimuli using iontophoresis were observed in the anterior cingulate cortex (BA24), the thalamus, the parietal cortex (BA40 and BA7), the dorsolateral prefrontal cortex (BA46) and the premotor cortex (BA6). We did not observe any changes in the secondary somatosensory cortex (S2) during the itching stimulus, corresponding to the previous imaging studies concerning itching. Activation in these areas related to itching stimuli was decreased by a simultaneous stimulation of itching and cold pain (the dual stimuli), as compared to itching alone. Interestingly, the midbrain, including periaqueductal gray matter (PAG), was only activated during the dual stimuli. PAG is well known to be a modulating noxious stimulus. Here we hypothesize that the activation of PAG may also be related to the itch modulation. These findings indicate that the modified brain activities in the PAG, the cingulate, the frontal and the parietal cortex might be associated with the itch modulation in the central nervous system and that the S2 might not be primarily involved in processing the itching perception in the brain since the activity of S2 was not observed in any concentration of itching stimuli.

Plasma arginine-8-vasopressin responses to osmotic or histamine stimulation contribute to the differential diagnosis of central diabetes insipidus.

The arginine-8-vasopressin (AVP) responses to osmotic and histamine stimuli were evaluated in 21 patients with central diabetes insipidus (CDI) and compared to those of 10 healthy controls. Plasma AVP was measured by radioimmunoassay. Following the infusion of 2.5% saline, the AVP responses of CDI patients fell into two distinct groups: CDI I gave no response at all, while CDI II responded subnormally. Histamine increased the plasma AVP level significantly in healthy volunteers. Patients with CDI II gave subnormal AVP responses to histamine. The AVP reactions of the patients with CDI I fell into two subgroups: CDI I/A had undetectable plasma AVP, while histamine evoked AVP release in CDI I/B. Histamine trial did not lead to any change in plasma osmolality. The authors conclude that patients with CDI II suffer from a partial CDI, while those with CDI I/A represent a complete form of the disease. The remainder (CDI I/B) presumably have an osmoreceptor failure. Osmotic and non-osmotic stimulation may provide a useful tool in the differential diagnosis of CDI.

Capillary, mast cell and connective tissue response to myxoviruses in the rat.

Myxoviruses injected intradermally into rats provoked activation of capillary endothelium, vasodilatation, increased capillary permeability, edema formation and severe disruption of the capillary wall without mastcell disruption, as visualized by the transparent skin techniques. Minute amounts of histamine and other stimuli, applied at the same site of the skin, further aggravated the vascular response to viruses and disrupted the perivascular mast cells. Neuraminidase, N-acetyl neuraminic acid, hyaluronidase and hyaluronic acid had a similar effect on the minute vessels, but there was no mast-cell disruption when histamine was injected at the same sites. Nasal discharge collected from a vasomotor rhinitis case, had no damaging effect on the capillaries. Nasal discharge from common cold cases, collected during the first three days of the onset provoked the same vascular damage as the myxoviruses. Samples collected at later periods did not effect the morphology of the capillaries. Vascular damage produced by the myxoviruses was not inhibited by levomepromazine, butazolidin or hydrocortisone.