Acute and subacute effects of oropharyngeal sensory stimulation with TRPV1 agonists in older patients with oropharyngeal dysphagia: a biomechanical and neurophysiological randomized pilot study

Noemí Tomsen, Omar Ortega, Laia Rofes, Viridiana Arreola, Alberto Martin, Lluís Mundet, Pere Clavé, Noemí Tomsen, Omar Ortega, Laia Rofes, Viridiana Arreola, Alberto Martin, Lluís Mundet, Pere Clavé

Abstract

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.

Keywords: deglutition disorders; neurophysiology; oropharyngeal dysphagia; therapeutics.

Conflict of interest statement

Conflict of interest statement: The authors declare no conflicts of interest in preparing this article.

Figures

Figure 1.
Figure 1.
Pharyngeal event-related potential (ERP) and scalp density maps to pharyngeal ERPs for acute (a) and subacute (b) studies. At the top of each treatment, ERP traces obtained at the Cz electrode for pretreatment (blue line) and post-treatment (red line) from the placebo group and capsaicinoids group after pharyngeal electrical stimulation are shown. Deflection at time point 0 corresponds to stimulus artefact. At the bottom, current scalp density maps at each ERP peak time point for each group are shown.
Figure 2.
Figure 2.
Correlation between the change in LVC time (left) and UOS closure time (right) and the reduction in the latency of N1 peak after the multiple-dose treatment. LVC, laryngeal vestibule closure; pERP, pharyngeal event-related potential; UOS: upper oesophageal sphincter.
Figure 3.
Figure 3.
Differences in LORETA source activity after acute stimulation (top) and subacute stimulation (bottom) compared with basal cortical activity. Coloured voxels represent areas of significant differences in activation (blue, increase; red, decrease) after correction for multiple comparisons.

References

    1. Clavé P, Shaker R. Dysphagia: current reality and scope of the problem. Nat Rev Gastroenterol Hepatol 2015; 12: 259–270.
    1. Ekberg O, Hamdy S, Woisard V, et al. Social and psychological burden of dysphagia: its impact on diagnosis and treatment. Dysphagia 2002; 17: 139–146.
    1. Baijens LWJ, Clavé P, Cras P, et al. European society for swallowing disorders – European Union Geriatric Medicine Society white paper: oropharyngeal dysphagia as a geriatric syndrome. Clin Interv Aging 2016; 11: 1403–1428.
    1. Rofes L, Arreola V, Romea M, et al. Pathophysiology of oropharyngeal dysphagia in the frail elderly. Neurogastroenterol Motil 2010; 22: 1–9.
    1. Ortega O, Rofes L, Martin A, et al. A comparative study between two sensory stimulation strategies after two weeks treatment on older patients with oropharyngeal dysphagia. Dysphagia 2016; 31: 706–716.
    1. Logemann JA, Rademaker AW, Pauloski BR, et al. Normal swallowing physiology as viewed by videofluoroscopy and videoendoscopy. Folia Phoniatr Logop 1998; 50: 311–319.
    1. Logemann J. Evaluation and treatment of swallowing disorders. Austin, TX: College-Hill Press, 1983.
    1. Kahrilas PJ, Lin S, Rademaker AW, et al. Impaired deglutitive airway protection: a videofluoroscopic analysis of severity and mechanism. Gastroenterology 1997; 113: 1457–1464.
    1. Robbins J, Langmore S, Hind JA, et al. Dysphagia research in the 21st century and beyond: proceedings from Dysphagia Experts Meeting, August 21, 2001. J Rehabil Res Dev 2002; 39: 543–548.
    1. Logemann JA, Pauloski BR, Alfred W, et al. Temporal and biomechanical characteristics of oropharyngeal swallow in younger and old men. J Speech Lang Hear Res 2000; 43: 1264–1674.
    1. Logemann JA, Pauloski BR, Alfred W, et al. Oropharyngeal swallow in younger and older women: videofluoroscopic analysis. J Speech Lang Hear Res 2002; 45: 434–445.
    1. Robbins J, Humpal NS, Banaszynski K, et al. Age-related differences in pressures generated during isometric presses and swallows by healthy adults. Dysphagia 2016; 31: 90–96.
    1. Hamdy S, Aziz Q, Rothwell JC, et al. The cortical topography of human swallowing musculature in health and disease. Nat Med 1996; 2: 1217–1224.
    1. Hamdy S, Aziz Q, Rothwell JC, et al. Cranial nerve modulation of human cortical swallowing motor pathways. Am J Physiol 1997; 272: G802–G808.
    1. Rofes L, Cola PC, Clave P. The effects of sensory stimulation on neurogenic oropharyngeal dysphagia. J Gastroenterol Hepatol Res 2014; 3: 1066–1072.
    1. Cabib C, Ortega O, Vilardell N, et al. Chronic post-stroke oropharyngeal dysphagia is associated with impaired cortical activation to pharyngeal sensory inputs. Eur J Neurol 2017; 24: 1355–1362.
    1. Rofes L, Ortega O, Vilardell N, et al. Spatiotemporal characteristics of the pharyngeal event-related potential in healthy subjects and older patients with oropharyngeal dysfunction. Neurogastroenterol Motil 2016; 29: 1–11.
    1. Rofes L, Arreola V, Martin A, et al. Natural capsaicinoids improve swallow response in older patients with oropharyngeal dysphagia. Gut 2013; 62: 1280–1287.
    1. Nakato R, Manabe N, Shimizu S, et al. Effects of capsaicin on older patients with oropharyngeal dysphagia: a double-blind, placebo-controlled, crossover study. Digestion 2017; 95: 210–220.
    1. Ebihara T, Sekizawa K, Nakazawa H, et al. Capsaicin and swallow reflex. Lancet 1993; 341: 432.
    1. Ebihara T, Takahashi H, Ebihara S, et al. Capsaicin troche for swallowing dysfunction in older people. J Am Geriatr Soc 2005; 53: 824–828.
    1. Ebihara T, Ebihara S, Yamazaki M, et al. Intensive stepwise method for oral intake using a combination of transient receptor potential stimulation and olfactory stimulation inhibits the incidence of pneumonia in dysphagic older adults. J Am Geriatr Soc 2010; 58: 196–198.
    1. Alvarez-Berdugo D, Rofes L, Arreola V, et al. A comparative study on the therapeutic effect of TRPV1, TRPA1, and TRPM8 agonists on swallowing dysfunction associated with aging and neurological diseases. Neurogastroenterol Motil 2018; 30: e13185.
    1. Clavé P, Arreola V, Romea M, et al. Accuracy of the volume-viscosity swallow test for clinical screening of oropharyngeal dysphagia and aspiration. Clin Nutr 2008; 27: 806–815.
    1. Mahoney FI, Barthel DW. Functional evaluation: the Barthel index. Md State Med J 1965; 14: 56–61.
    1. Kaiser MJ, Bauer JM, Ramsch C, et al. Validation of the Mini Nutritional Assessment short-form (MNA-SF): a practical tool for identification of nutritional status. J Nutr Health Aging 2009; 13: 782–788.
    1. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373–383.
    1. Baijens LW, Speyer R, Passos VL, et al. Swallowing in Parkinson patients versus healthy controls: reliability of measurements in videofluoroscopy. Gastroenterol Res Pract 2011; 2011: 380682.
    1. Hind JA, Gensler G, Brandt DK, et al. Comparison of trained clinician ratings with expert ratings of aspiration on videofluoroscopic images from a randomized clinical trial. Dysphagia. 2009; 24: 211–217.
    1. Kelly AM, Drinnan MJ, Leslie P. Assessing penetration and aspiration: how do videofluoroscopy and fiberoptic endoscopic evaluation of swallowing compare? Laryngoscope 2007; 117: 1723–1727.
    1. Rosenbek JC, Robbins JA, Roecker PDEB, et al. A penetration-aspiration scale. Dysphagia 1996; 11: 93–98.
    1. Klem GH, Lüders HO, Jasper HH, et al. The ten-twenty electrode system of the International Federation. The International Federation of Clinical Neurophysiology. Electroencephalogr Clin Neurophysiol Suppl 1999; 52: 3–6.
    1. Ertekin C. Voluntary versus spontaneous swallowing in man. Dysphagia 2011; 26: 183–192.
    1. Toogood JA, Smith RC, Stevens TK, et al. Swallowing preparation and execution: insights from a delayed-response functional magnetic resonance imaging (fMRI) study. Dysphagia 2017; 32: 526–541.
    1. Alvarez-Berdugo D, Rofes L, Farré R, et al. Localization and expression of TRPV1 and TRPA1 in the human oropharynx and larynx. Neurogastroenterol Motil 2016; 28: 91–100.
    1. Teismann IK, Suntrup S, Warnecke T, et al. Cortical swallowing processing in early subacute stroke. BMC Neurol 2011; 11: 34.
    1. Suntrup-Krueger S, Bittner S, Recker S, et al. Electrical pharyngeal stimulation increases substance P level in saliva. Neurogastroenterol Motil 2016; 28: 855–860.

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