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Background: Older people with oropharyngeal dysphagia (OD) present a decline in pharyngeal sensory function. The aim of this proof-of-concept study was to assess the biomechanical and neurophysiological effects of acute and subacute oropharyngeal sensory stimulation with transient receptor potential vanilloid 1 (TRPV1) agonists (capsaicinoids) in older patients with OD. Methods: We studied the effect of a single dose versus multiple doses (2 weeks) of oral capsaicin treatment (10–5 M) or placebo in 28 older patients with OD (81.2 ± 4.6 years) using videofluoroscopy (penetration-aspiration scale [PAS], timing of swallow response) and electroencephalography (EEG) (latency and amplitude of pharyngeal event-related potential [ERP]). Results: Acute stimulation by capsaicinoids 10–5 M did not improve swallow function and did not produce significant changes in pharyngeal ERP. In contrast, after 10 days of treatment, patients presented a clinically relevant and statistically significant reduction in the laryngeal vestibule closure (LVC) time (22.5%, p = 0.042), and in the PAS (24.2%, p = 0.038), compared with the placebo group. EEG results showed a reduction in the latency of the N1 peak (28.6%, p = 0.007) and an increase of the amplitude of the P1-N2 (59.4%, p = 0.038) and the N2-P2 (43.6%, p = 0.050) peaks. We observed a strong and significant correlation between the reduction in the latency of the N1 peak and change in LVC time after subacute treatment ( r = 0.750, p = 0.003). Conclusions: After 2 weeks of treatment, oropharyngeal sensory stimulation with capsaicinoids induced cortical changes that were correlated with improvements in swallowing biomechanics in older patients with OD. These results further show that sensory stimulation by TRPV1 agonists can become a useful pharmacological treatment for older patients with OD.

Background: Otilonium bromide (OB) is a spasmolytic agent acting as an L-type calcium channel antagonist in intestinal and colonic smooth muscle cells (SMCs). We analyzed three independent clinical trials with homogeneous design on patients with irritable bowel syndrome (IBS). After 2 weeks receiving placebo, patients were randomized to receive OB (3 × 40 mg daily) or placebo for 15 weeks. We aimed to perform a pooled analysis of the data from these homogeneous clinical trials to evaluate the efficacy of OB treatment on symptoms and global response of patients. Methods: A total of 883 patients with IBS (69.8% women, mean age 46.2 years, 43.8% mixed type) were included, 442 treated with OB and 441 with placebo. The efficacy results from the three studies at weeks 5, 10 and 15 were pooled in an intention-to-treat (ITT) strategy, analyzed with a logistic regression model and described by forest plots. Results: Despite a placebo effect in all efficacy variables, a significant therapeutic effect of OB was observed at weeks 10 and 15 with reference to: (a) intensity and frequency of abdominal pain; (b) rate of responders as evaluated by patients (71.8% at week 10 and 77.2% at week 15); (c) severity of bloating; (d) rate of responders as evaluated by physicians (55% at week 10 and 63.9% at week 15). No significant OB effect was observed in stool frequency and consistency. Conclusions: OB is more effective than placebo in IBS treatment. Therapeutic benefits are significant after 10 weeks and are maximal after 15 weeks of treatment.

Otilonium bromide (OB) is a spasmolytic compound of the family of quaternary ammonium derivatives and has been successfully used in the treatment of patients with irritable bowel syndrome (IBS) due to its specific pharmacodynamic effects on motility patterns in the human colon and the contractility of colonic smooth muscle cells. This article examines how. OB inhibits the main patterns of human sigmoid motility in vitro, which are spontaneous rhythmic phasic contractions, smooth muscle tone, contractions induced by stimulation of excitatory motor neurons and contractions induced by direct effect of excitatory neurotransmitters. It does this mainly by blocking calcium influx through L-type calcium channels and interfering with mobilization of cellular calcium required for smooth muscle contraction, thereby limiting excessive intestinal contractility and abdominal cramping. OB also inhibits T-type calcium channels and muscarinic responses. Finally, OB inhibits tachykinin receptors on smooth muscle and primary afferent neurons which may have the joint effect of reducing motility and abdominal pain. All these mechanisms mediate the therapeutic effects of OB in patients with IBS and might be useful in patients with other spastic colonic motility disorders such as diverticular disease.