Capsaicin nasal spray is used in daily practice against IR without knowledge about the exact mechanisms involved in this treatment. Therefore, this study aims to address this issue by studying the functional (electrophysiologic) changes after specific stimulations in IR patients and healthy controls before and after capsaicin/placebo treatment.

As an essential step towards the improvement of the treatment of IR we will investigate the neural mechanisms underlying the therapeutic action of capsaicin. In particular, we plan to evaluate the effects of capsaicin on the functional properties of the innervation of nasal mucosa by monitoring the trigeminal nerve activity using measurements of negative mucosa potentials (NMP). NMPs, will be evoked by chemical and thermal stimuli in IR patients and healthy controls. Considering the evidence suggesting a role of sensory C-fibers in the pathophysiology of IR, we will employ low concentrations of irritants that specifically activate receptors expressed in those fibers, i.e., capsaicin for TRPV1 and cinnamaldehyde and allyl-isothiocyanate (mustard oil) for TRPA1. The same stimulations will be performed immediately after capsaicin treatment, and after 4 weeks, 3 months and 6 months. This will allow for an objective assessment of the functionality of the C-fiber innervation before the treatment, during the phase of therapeutic response and during the period of recurrence of the IR symptoms. The results of the NMP measurements will be contrasted with the therapeutic response and with evaluations of nasal congestion, nasal sensitivity and the presence of neuro-mediators found in nasal biopsies. Importantly, the independent assessment of the NMP responses mediated by either TRPV1 or TRPA1 will allow determining the specific role of these nociceptors in the pathophysiology of IR, which, in turn, may help to design more specific and effective therapies.

Inclusion Criteria:

1. Patients with persistent (> 52w) rhinological symptoms: nasal discharge, sneezing, congestion for an average of at least 1 h per day for at least 5 days during a period of 14 days, negative skin prick test or negative RAST, and without structural abnormalities explaining nasal obstruction will be proposed to participate in the trial.
2. Age > 18 and < 60 years
3. Written informed consent
4. Willingness to adhere to visit schedules
5. Adequate contraceptive precautions in female patients with childbearing potential
6. Unresponsiveness to nasal steroid spray (4 weeks of use)

Exclusion Criteria:

1. Age < 18 and > 60 years
2. Patients with AR, demonstrated by either positive skin prick test or RAST
3. Asthma
4. Structural abnormalities: nasal polyps, severe septal deviation (septum reaching concha inferior or lateral nasal wall.
5. Systemic steroid treatment less than 4 weeks before the inclusion in the study.
6. Nasal steroid spray less than 4 weeks before the inclusion, oral leukotriene antagonists or long-acting antihistamines less than 2 weeks before the inclusion.
7. Inability of the patient to stop taking medication affecting nasal function.
8. Evidence of infectious rhinitis/rhinosinusitis.