P. Stjärne

Capsaicin and nicotine-sensitive afferent neurones and nasal secretion in healthy human volunteers and in patients with vasomotor rhinitis.

1 Applications of capsaicin, nicotine and methacholine were made locally onto the nasal mucosa in human controls and patients suffering from hyperreactive nasal disorders. Perception of sensation was registered as a sympton score and secretion quantified. The sensory reaction (irritation ‐pain) to capsaicin was similar in the three groups studied, i.e. controls, a group of patients with the diagnosis of vasomotor rhinitis and a group of patients with increased nasal secretion as the main symptom of the hyperreactive disorder. Nicotine induced only a mild itching sensation in the three groups. However, capsaicin and nicotine challenge caused a significantly larger secretory response in the last group than in the unselected vasomotor rhinitis group and in the control group. 2 Pretreatment with muscarinic receptor antagonists almost completely abolished the secretory response to both capsaicin and nicotine, and blocked methacholine‐induced secretion. Furthermore, pretreatment with a combination of local anaesthetic and vasoconstrictor agent abolished the capsaicin‐induced irritation, as well as the capsaicin‐ and nicotine‐induced secretion on both the ipsilateral and the contralateral side. Therefore, no clearcut contribution seems to be exerted by locally released peptides from sensory neurones as direct trigger substances for the secretory response to capsaicin. 3 In conclusion, the nasal secretory response, in man, to both capsaicin and nicotine, seems to be mediated via cholinergic parasympathetic reflexes. In patients with hyperreactive non‐allergic disorders of the nasal mucosa with rhinorrhea as the main complaint, the enhanced secretion may be due to a hyperreactive efferent cholinergic mechanism rather than hypersensitive irritant receptors on capsaicin‐ and nicotine‐sensitive sensory neurones. Challenge with irritant agents seems a useful test for the evaluation of both afferent and efferent reflexogenic responses in hyperreactive disorders of the nasal mucosa.

Capsaicin Desensitization of the Nasal Mucosa Reduces Symptoms upon Allergen Challenge in Patients with Allergic Rhinitis

Patients with birch pollen allergic rhinitis were treated locally, out of season, in the nasal cavity with capsaicin (30 microM) or saline. The capsaicin treatment resulted in a statistically significant reduction of symptoms upon allergen challenge, which lasted for 2 months. Saline had no effect on the symptom score upon allergen challenge. Neither capsaicin nor saline treatment had any effect on allergen challenge-induced nasal mucosal swelling monitored by acoustic rhinometry. Allergen challenge-induced eosinophil migration to the nasal mucosa was affected by neither capsaicin nor the saline treatment. The finding that capsaicin treatment reduces allergic symptoms indicates that selective, non-peptide neurokinin receptor antagonists may be an alternative in the future in the treatment of nasal allergy. However, owing to the pain involved in local capsaicin treatment this treatment is unlikely to be of clinical use.

Release of calcitonin gene-related peptide in the pig nasal mucosa by antidromic nerve stimulation and capsaicin

The overflow of calcitonin gene-related peptide like-immunoreactivity (CGRP-LI) in the nasal venous effluent upon antidromic stimulation of the maxillary division of the trigeminal nerve with 6.9 Hz for 3 min or upon capsaicin (0.3 mumol bolus injection) were analysed in the nasal mucosa of sympathectomized pentobarbital anaesthetized pigs. The overflow of CGRP-LI upon antidromic stimulation displayed a slower appearance in the venous effluent than the overflow upon bolus injection of capsaicin. The vascular effects as revealed by the arterial blood flow, the venous blood flow, the blood volume of the nasal mucosa, i.e., the filling of the capacitance vessels and the superficial mucosal blood flow as revealed by the laser-Doppler signal were also studied. Antidromic stimulation of the trigeminal nerve as well as capsaicin bolus injection induced a marked vasodilation which was parallel to the overflow of CGRP. However, capsaicin bolus injection also resulted in a marked increase in the mean arterial blood pressure which may be due to reflex activation of sympathetic fibers. In conclusion, we have demonstrated that chemical stimulation with capsaicin as well as antidromic stimulation of nasal sensory nerves in sympathectomized animals induces both vasodilation and overflow of CGRP-LI in vivo. This indicates that CGRP may contribute to the sensory regulation of the microcirculation in the nasal mucosa.

Significance of endogenous glucocorticoid sensitivity for airway eosinophilia in a murine model of allergy.

Conclusions Endogenous GC protects against allergic inflammatory responses in the airways. These effects are modulated by both peripheral blockade and inhibition of release. Individual response patterns to stress, i.e. corticosterone release and peripheral sensitivity, may influence both the central and peripheral levels of the allergic airway reaction in patients. Objective Glucocorticoids (GCs) modulate the allergic inflammatory response. Acute or chronic stress will influence circulating levels of GCs, rates of secretion, metabolism and target tissue sensitivity. In a clinical situation, stress may exacerbate or attenuate the asthmatic reaction. The aim of this study was to investigate the effects of inhibition of endogenous GC in an allergic airway inflammation model in the mouse. Material and methods An ovalbumin model using i.p. sensitization and intra-nasal challenge was used for respiratory eosinophilic inflammation. GC release was inhibited by administration of metyrapone (ME), and peripheral glucocorticoid receptors were blocked by administration of RU486 (RU). Results Inhibition with RU and ME increased eosinophilia in the bone marrow compared to controls (p<0.05). Eosinophilia in bronchoalveolar lavage fluid increased in the sensitized groups compared to controls, but there were no differences between the sensitized groups. CD3+ and CD4+ cells were increased in the nasal mucosa as a result of treatment with RU and ME.

Mechanical Stimulation and Capsaicin Evoked Vasodilation by Parasympathetic Reflex Mechanisms in the Pig Nasal Mucosa

A model was developed using pentobarbital anesthetized pigs to study bilateral blood flow changes in the nasal mucosa by flow-probes on both sphenopalatine arteries. Unilateral mechanical stimulation of the nasal mucosa for 10s as well as close intra-arterial capsaicin infusion induced bilateral vasodilation. The magnitude of the vasodilator responses were similar on both sides, although the capsaicin effect (maximal increase in arterial blood flow by about 100 ml/min) was larger than that of the mechanical stimulation. Pretreatment with atropine (0.5 mg x kg-1) had no effect on the vascular responses to capsaicin or mechanical stimulation. However, when the pigs were pretreated with the ganglionic nicotinic receptor blocking agent, chlorisondamine (3 mg x kg-1), the vasodilatory responses to mechanical stimulation were abolished and the responses to capsaicin infusion markedly reduced (90-95%). These data indicate that unilateral mechanical stimulation as well as capsaicin infusion evoke bilateral nasal vasodilation which is probably mediated via a central reflex arch with a parasympathetic non-cholinergic final step.