Effect of Aging, Gender and Sensory Stimulation of TRPV1 Receptors with Capsaicin on Spontaneous Swallowing Frequency in Patients with Oropharyngeal Dysphagia: A Proof-of-Concept Study

Weslania Nascimento, Noemí Tomsen, Saray Acedo, Cristina Campos-Alcantara, Christopher Cabib, Marta Alvarez-Larruy, Pere Clavé, Weslania Nascimento, Noemí Tomsen, Saray Acedo, Cristina Campos-Alcantara, Christopher Cabib, Marta Alvarez-Larruy, Pere Clavé

Abstract

Spontaneous swallowing contributes to airway protection and depends on the activation of brainstem reflex circuits in the central pattern generator (CPG). We studied the effect of age and gender on spontaneous swallowing frequency (SSF) in healthy volunteers and assessed basal SSF and TRPV1 stimulation effect on SSF in patients with post-stroke oropharyngeal dysphagia (OD). The effect of age and gender on SSF was examined on 141 healthy adult volunteers (HV) divided into three groups: GI-18-39 yr, GII-40-59 yr, and GIII->60 yr. OD was assessed by the Volume-Viscosity Swallowing Test (VVST). The effect of sensory stimulation with capsaicin 10-5 M (TRPV1 agonist) was evaluated in 17 patients with post-stroke OD, using the SSF. SSF was recorded in all participants during 10 min using surface electromyography (sEMG) of the suprahyoid muscles and an omnidirectional accelerometer placed over the cricothyroid cartilage. SSF was significantly reduced in GII (0.73 ± 0.50 swallows/min; p = 0.0385) and GIII (0.50 ± 0.31 swallows/min; p < 0.0001) compared to GI (1.03 ± 0.62 swallows/min), and there was a moderate significant correlation between age and SFF (r = -0.3810; p < 0.0001). No effect of gender on SSF was observed. Capsaicin caused a strong and significant increase in SSF after the TRPV1 stimulation when comparing to basal condition (pre-capsaicin: 0.41 ± 0.32 swallows/min vs post-capsaicin: 0.81 ± 0.51 swallow/min; p = 0.0003). OD in patients with post-stroke OD and acute stimulation with TRPV1 agonists caused a significant increase in SSF, further suggesting the potential role of pharmacological stimulation of sensory pathways as a therapeutic strategy for CPG activation in patients with OD.

Keywords: TRPV Cation Channels; aging; capsaicin; disorders; spontaneous swallowing frequency; stroke.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Study design of the two populations included in the study: HV at the top, post-stroke patients at the bottom.
Figure 2
Figure 2
SSF and its correlation with age in HV: (A) SSF results by age groups; (B) correlation between SSF and age. SSF: spontaneous swallowing frequency; GI: 18–39 years age group; GII: 40–59 years age group; GIII: ≥60 years age group; * p < 0.05; **** p < 0.0001.
Figure 3
Figure 3
Gender effect on SSF: (A) SSF results by age groups in women; (B) correlation between SSF and age in women; (C) SSF results by age groups in men; (D) correlation between SSF and age in men. SSF: spontaneous swallowing frequency; GI: 18–39 years age group; GII: 40–59 years age group; GIII: ≥60 years age group; * p < 0.05; ** p < 0.01.
Figure 4
Figure 4
EMG metrics (Amplitude and Delta T) in all HV (A), women (B), and men (C). ∆T: Delta T; s: seconds; GI: 18–39 years group; GII: 40–59 years group; GIII: ≥60 years group; * p < 0.05; ** p < 0.01; **** p < 0.0001.
Figure 5
Figure 5
EMG metrics in PSD patients and GIII group: (A) amplitude, (B) Delta T, and (C) AUC. ∆T: Delta T; AUC: area under the curve; s: seconds; GIII: ≥60 years group; PSD: post-stroke dysphagia; ** p < 0.01; *** p < 0.001; **** p < 0.0001.
Figure 6
Figure 6
Capsaicin effect on SSF and EMG metrics in post-stroke dysphagia patients: (A) SFF, (B) Amplitude. SSF: spontaneous swallowing frequency; s: seconds; pre: pre-treatment; post: post-treatment; *** p < 0.001.
Figure 7
Figure 7
Pre- and post-capsaicin stimulation SSF registration. Red line represents the electromyography (EMG) signal; green line represents the EMG integrated signal; blue line represents the accelerometer movement; black arrows point to each swallow registered.

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