Vagal and spinal sensory afferent innervation are responsible for to regulation of neurogenic inflammation in the airways. Neurogenic inflammation is a complex process involving vasodilatation,plasma protein extravasation and edema,glandular secretion and immunoinflammatory cell chemotaxis and activation. Plasma extravasation is the result of the activation of sensory nerve endings and the subsequent prodution of neuropeptides, namely, tachykinins such as substance P, neurokinin A and neurokinin B. SP was more potent than NKA or NKB in increasing microvascular permeability, which indicate that tachykinin NK-1 receptors are mainly involved in neurogenic inflammation in the airways of rat. When 6-hydroxydopamine¡]6-OHDA¡^was infused into the tracheal lumen,it causes plasma extravasation in the tracheal mucosa mediated by sensory nerve axons. Local application of 6-OHDA to stellate ganglion, had no effect on neurogenic inflammation and SP-IR innervation in the airways.The present study was to investigate the effect of intravenous injection of 6-OHDA on plasma leakage in the airways.This study also used the NK-1 receptor antagonist L-732,138 to investigate if 6-OHDA-induced plasma leakage in the airways was related to NK-1 receptors. India ink was used as tracer dye to label the leaky microvessels to evaluate the magnitude of inflammation . We found that 6-OHDA in the doses of 25 mg/kg and 50 mg/kg caused an extensive increase in plasma extravasation in the trachea and bronchi. But the vehicle¡]1 ¢ML-ascorbic acid and 0.4 ¢MNaCl, pH 3.4¡^caused a slight plasma leakage. Intravenous administration of L-732,138 decrease 6-OHDA induced plasma leakage. But one week after vagal transection, 6-OHDA-induced plasma extravasation in the ipsilateral airways was not significatly reduced. It is suggested that intravenous 6-OHDA stimulated bronchopulmonary C-fibers and resulted in vagal C-fiber release of tachykinins that produced acute inflammation in the lower airways. Intravenous application of L-732,138 significantly reduced the 6-OHDA-induced plasma leakage, suggesting that NK-1 receptors in the venular endothelial cells mediate the inflammatory response in the layynx,trachea,bronchi.and esophagus of the rat .

Skin blood flow (SKBF) demonstrates a biphasic response to innocuous, local heating. Much about the mechanism of the first phase is unknown. A type of ion channel (TRPV3) sensitive to and increasingly activated by temperatures from ~33 to ~45°C may be involved. TRPV3 channels are abundantly located in the keratinocytes and are believed to elicit the release of ATP, a putative cutaneous vasodilator, upon activation. This study investigated the possibility that TRPV3 channels and ATP have a role in the first phase of the SBKF response to local heat. Fifteen young, healthy subjects participated in the study. Two microdialysis probes were inserted into the dermis on the forearm. Using a peltier module, the skin above the probes (3cm x 3cm) was heated to 31, 35, 39, and 43°C to manipulate the level of activation of TRPV3 channels for eight minutes each. The probes were perfused with 0.9% saline at 2µl/min. Dialysate from each phase was analyzed for the concentration of ATP ([ATP]d). Cutaneous vascular conductance (CVC), measured by laser Doppler flowmetry, was monitored throughout. The [ATP]d decreased significantly when the skin was heated to temperatures known to strongly activate TRPV3 channels (i.e 39 and 43°C). [ATP]d demonstrated no relationship with CVC and only a very weak relationship with peltier temperature (r2 = 0.02, p<0.05). These data indicate that local heating and presumably heat-induced activation of the TRPV3 channels results in the decrease, not increase, of the release of ATP in human skin, and that the [ATP]d is not related to changes in skin blood flow. Significant dilation was observed at 35°C. This threshold, which is several degrees lower than the threshold previously reported, suggests that the TRPV3 channels may be involved in the dilator response in some way independent of interstitial ATP.

Background: In Parkinson’s disease (PD), alpha-synuclein accumulation in cutaneous autonomic pilomotor and sudomotor nerve fibers has been linked to autonomic nervous system disturbances even in the early stages of the disease. This study aims to assess the association between alpha-synuclein-mediated structural autonomic nerve fiber damage and function in PD, elucidate the role of neuropathy progression during the early disease stages, and test reproducibility and external validity of pilomotor function assessment using quantitative pilomotor axon-reflex test and sudomotor function via quantitative direct and indirect test of sudomotor function. Methods/design: A prospective controlled study will be conducted at four study sites in Europe and the USA. Fifty-two male and female patients with idiopathic PD (Hoehn and Yahr 1–2) and 52 age- and sex-matched healthy controls will be recruited. Axon-reflex-mediated pilomotor erection will be induced by iontophoresis of phenylephrine on the dorsal forearm. Silicone impressions of the response will be obtained, scanned, and quantified for pilomotor muscle impressions by number, impression size, and area of axon-reflex spread. Axon-reflex-mediated sweating following acetylcholine iontophoresis will be quantified for number and size of droplets and axon-reflex spread. Sympathetic skin responses, autonomic and motor symptoms will be evaluated. Tests will be performed at baseline, after 2 weeks, 1, 2, and 3 years. Skin biopsies will be obtained at baseline and after 3 years and will be analyzed for nerve fiber density and alpha-synuclein accumulation. Discussion: We anticipate that progression of autonomic nerve dysfunction assessed via pilomotor and sudomotor axon-reflex tests is related to progression of autonomic symptom severity and alpha-synuclein deposition. Potential applications of the techniques include interventional studies evaluating disease-modifying approaches and clinical assessment of autonomic dysfunction in patients with PD.

Rosacea is a chronic skin disorder, characterized by redness and flushing of the cheeks, nose, chin or forehead. It has been proposed that rosacea is a result of frequent blushing (Miller, 1921; Klaber & Whittkower, 1939). However, the relationship between rosacea and blushing is uncertain. The aim of the present research was to investigate the relationship between psychological stress and vascular disturbances in rosacea. Five studies were conducted. The first study explored the relationship between rosacea and mental health while the next two investigated vascular responses in rosacea sufferers and controls to acetylcholine (which induces endothelial vasodilatation and axon reflexes) and psychological stress (embarrassment). The fourth study aimed to examine the relationship between psychological indicators and rosacea symptoms on a daily basis. The fifth study consisted of three case studies looking at the use of Cognitive Behavioural Therapy (CBT) and Task Concentration Training (TCT) with rosacea sufferers presenting with social anxiety and fear of blushing symptoms. In study 1, sixty-two participants were asked to complete the Blushing Propensity Scale (BPS), Fear of Negative Evaluation (FNE), Depression, Anxiety and Stress Scale (DASS), Social Interaction Anxiety Scale (SIAS) and Social Phobia Scale (SPS). Outcomes from the first study indicated that Type 2 rosacea sufferers (n= 12) perceived themselves as blushing more frequently and intensely than Type 1 rosacea sufferers (n=19) or controls (n=31). This suggested that Type 2 rosacea sufferers experiencing frequent blushing may have a lower sensitivity threshold to blushing episodes. In addition, Type 2 rosacea sufferers perceived themselves as more stressed than Type 1 rosacea sufferers or controls, possibly indicating that managing the condition can be stressful. Contrary to previous reports (Gupta et al., 2006; National Rosacea Society, 2005) severity of rosacea was not associated with depression, social anxiety or fear of negative evaluation. However, a few participants who reported high social anxiety and stress scores were offered psychological intervention (Study 5). The aim of the second study was to investigate vascular responses in rosacea sufferers. Cutaneous endothelial and axon reflex function was assessed using an acetylcholine dose response curve. The axon reflex was assessed by inducing a flare with ACh iontophoresis. Outcomes from this study indicated that Type 2 rosacea sufferers had a greater axon reflex response than Type 1 rosacea sufferers. Thus over-reactivity of the axon reflex in Type 2 rosacea sufferers might contribute to prolonged vasodilatation. However, cutaneous endothelial responses to ACh were similar in rosacea and control groups. The results suggested that neural pathways mediated the flushing response rather than cutaneous endothelial function. The third study investigated facial blood flow while participants attempted laboratory induced embarrassment tasks. Type 2 rosacea sufferers were found to have a greater blood flow in the facial region than Type 1 rosacea sufferers during singing and speech tasks, suggesting that Type 2 rosacea sufferers blushed more than type 1 rosacea sufferers or controls. Furthermore, Type 2 rosacea sufferers reported higher embarrassment and blushing ratings than Type 1 rosacea sufferers. This indicated that Type 2 rosacea sufferers perceived themselves as emotionally more aroused than other participants. Taken together, it would appear that a combination of physiological and cognitive factors increased facial blood flow in Type 2 rosacea sufferers in laboratory induced embarrassment tasks. The fourth study explored the relationship between stress and symptoms of rosacea. Using a diary, 15 rosacea sufferers recorded their stress, anxiety and mood and their intensity of rosacea symptoms daily. Stress was associated with increased stinging/facial redness on the same day for 1 to 2 months. Furthermore, it was associated with increased stinging ratings the next day. However, feeling anxious or having low mood was not related to increase stinging the next day. The presence of increased stress found in rosacea participants on the day where stinging and redness occurred should be taken into consideration when formulating psychological interventions for rosacea sufferers. In study 5, individual psychological intervention was provided to three participants experiencing stress, fear of blushing and social anxiety symptoms. Cognitive Behavioural Therapy (CBT) and Task Concentration Training (TCT) were helpful in managing stress, anxiety and fear of blushing symptoms in individual rosacea sufferers. Encouragingly, all participants reported a gain in their repertoire of strategies and showed a decrease in anxiety symptoms on assessment questionnaires following their intervention. Replication of the intervention protocol and investigation of other psychological approaches are required to establish best practise outcome for rosacea sufferers who require psychological interventions. The present findings suggest that over-reactivity of axon reflexes contributes to facial flushing. In addition, emotional flushing in rosacea sufferers appears to be maintained by a combination of cognitive and physiological factors. On a clinical level, the study recommends that emotional stress associated with facial flushing in rosacea sufferers to be targeted for psychological intervention.

Background: In Parkinson’s disease (PD), alpha-synuclein accumulation in cutaneous autonomic pilomotor and sudomotor nerve fibers has been linked to autonomic nervous system disturbances even in the early stages of the disease. This study aims to assess the association between alpha-synuclein-mediated structural autonomic nerve fiber damage and function in PD, elucidate the role of neuropathy progression during the early disease stages, and test reproducibility and external validity of pilomotor function assessment using quantitative pilomotor axon-reflex test and sudomotor function via quantitative direct and indirect test of sudomotor function. Methods/design: A prospective controlled study will be conducted at four study sites in Europe and the USA. Fifty-two male and female patients with idiopathic PD (Hoehn and Yahr 1–2) and 52 age- and sex-matched healthy controls will be recruited. Axon-reflex-mediated pilomotor erection will be induced by iontophoresis of phenylephrine on the dorsal forearm. Silicone impressions of the response will be obtained, scanned, and quantified for pilomotor muscle impressions by number, impression size, and area of axon-reflex spread. Axon-reflex-mediated sweating following acetylcholine iontophoresis will be quantified for number and size of droplets and axon-reflex spread. Sympathetic skin responses, autonomic and motor symptoms will be evaluated. Tests will be performed at baseline, after 2 weeks, 1, 2, and 3 years. Skin biopsies will be obtained at baseline and after 3 years and will be analyzed for nerve fiber density and alpha-synuclein accumulation. Discussion: We anticipate that progression of autonomic nerve dysfunction assessed via pilomotor and sudomotor axon-reflex tests is related to progression of autonomic symptom severity and alpha-synuclein deposition. Potential applications of the techniques include interventional studies evaluating disease-modifying approaches and clinical assessment of autonomic dysfunction in patients with PD.