Skip to main content
SpringerLink
Log in

Oropharyngeal Dysphagia in Older People is Associated with Reduced Pharyngeal Sensitivity and Low Substance P and CGRP Concentration in Saliva

  • Original Article
  • Published:
Dysphagia Aims and scope Submit manuscript

Abstract

Substance P (SP) and Calcitonine gene-related peptide (CGRP) are released by sensory nerve fibers in the oropharynx. Patients with oropharyngeal dysphagia (OD) present reduced oropharyngeal sensitivity and low SP concentration in saliva. We aimed to assess the concentration of salivary SP and CGRP in healthy volunteers, and older people without and with OD, and the relationship with pharyngeal sensory threshold. We included 15 healthy volunteers, 14 healthy elderly and 14 elderly with OD. Swallow function was assessed by videofluoroscopy (VFS). Pharyngeal sensory threshold was assessed by intrapharyngeal electrical stimulation. Hydration and phase angle were assessed by bioimpedance. Saliva samples were collected with a Salivette® to determine SP and CGRP concentration by ELISA. Elderly patients with OD presented impaired safety of swallow (PAS 4.38 ± 0.77 p < 0.0001 vs. healthy volunteers = 1 and healthy elderly = 1.43 ± 0.51). Healthy elderly and elderly with OD presented a reduction in intracellular water and saliva volume (healthy elderly, 592.86 ± 327.79 μl, p = 0.0004; elderly with OD, 422.00 ± 343.01 μl, p = 0.0001 vs healthy volunteers, 1333.33 ± 615.91 μl, r = 0.6621, p < 0.0001). Elderly patients with OD presented an impairment in pharyngeal sensory threshold (10.80 ± 3.92 mA vs. healthy volunteers, 5.74 ± 2.57 mA; p = 0.007) and a reduction in salivary SP (129.34 pg/ml vs. healthy volunteers: 173.89 pg/ml; p = 0.2346) and CGRP levels (24.17 pg/ml vs. healthy volunteers: 508.18 pg/ml; p = 0.0058). There was a negative correlation between both SP and CGRP concentrations and pharyngeal sensory threshold (r = − 0.450, p = 0.024; r = − 0.4597, p = 0.036, respectively), but only SP identified elderly patients with OD with higher pharyngeal sensory threshold. Elderly patients with OD presented hydropenia and sarcopenia, reduced salivary SP and CGRP and impaired pharyngeal sensitivity. Our study suggests SP levels in saliva as a potential biomarker to monitor pharyngeal sensitivity in elderly patients with OD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Serra-Prat M, Hinojosa G, López D, Juan M, Fabré E, Voss DS, et al. Prevalence of oropharyngeal dysphagia and impaired safety and efficacy of swallow in independently living older persons. J Am Geriatr Soc. 2011;59:186–7. https://doi.org/10.1111/j.1532-5415.2010.03227.x.

    Article  PubMed  Google Scholar 

  2. World Health Organization (2010) International Classification of Diseases (ICD). Geneva.

  3. Baijens LWJ, Clavé P, Cras P, Ekberg O, Forster A, Kolb GF, et al. European society for swallowing disorders—European union geriatric medicine society white paper: oropharyngeal dysphagia as a geriatric syndrome. Clin Interv Aging. 2016;11:1403–28. https://doi.org/10.2147/CIA.S107750.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Rofes L, Arreola V, Romea M, Palomeras E, Almirall J, Cabré M, et al. Pathophysiology of oropharyngeal dysphagia in the frail elderly. Neurogastroenterol Motil. 2010;22:851–9. https://doi.org/10.1111/j.1365-2982.2010.01521.x.

    Article  CAS  PubMed  Google Scholar 

  5. Rofes L, Ortega O, Vilardell N, Mundet L, Clavé P. Spatiotemporal characteristics of the pharyngeal event-related potential in healthy subjects and older patients with oropharyngeal dysfunction. Neurogastroenterol Motil. 2017;29:1–11. https://doi.org/10.1111/nmo.12916.

    Article  PubMed  Google Scholar 

  6. Moayedi Y, Duenas-Bianchi LF, Lumpkin EA. Somatosensory innervation of the oral mucosa of adult and aging mice. Sci Rep. 2018;8:1–14. https://doi.org/10.1038/s41598-018-28195-2.

    Article  CAS  Google Scholar 

  7. Mortelliti AJ, Malmgren LT, Gacek RR. Ultrastructural changes with age in the human superior laryngeal nerve. Arch Otolaryngol Neck Surg. 1990;116:1062–9. https://doi.org/10.1001/archotol.1990.01870090078013.

    Article  CAS  Google Scholar 

  8. Alvarez-Berdugo D, Rofes L, Farré R, Casamitjana JF, Enrique A, Chamizo J, et al. Localization and expression of TRPV1 and TRPA1 in the human oropharynx and larynx. Neurogastroenterol Motil. 2016;28:91–100. https://doi.org/10.1111/nmo.12701.

    Article  CAS  PubMed  Google Scholar 

  9. Alvarez-Berdugo D, Rofes L, Casamitjana JF, Enrique A, Chamizo J, Viña C, et al. TRPM8, ASIC1, and ASIC3 localization and expression in the human oropharynx. Neurogastroenterol Motil. 2018;30:5–7. https://doi.org/10.1111/nmo.13398.

    Article  CAS  Google Scholar 

  10. Clavé P, Shaker R. Dysphagia: current reality and scope of the problem. Nat Rev Gastroenterol Hepatol. 2015;12:259–70. https://doi.org/10.1038/nrgastro.2015.49.

    Article  PubMed  Google Scholar 

  11. Rodrigo J, Polak JM, Terenghi G, Cervantes C, Ghatei MA, Mulderry PK, et al. Calcitonin gene-related peptide (CGRP)-immunoreactive sensory and motor nerves of the mammalian palate. Histochemistry. 1985;82:67–74. https://doi.org/10.1007/BF00502092.

    Article  CAS  PubMed  Google Scholar 

  12. Barbariga M, Fonteyne P, Ostadreza M, Bignami F, Rama P, Ferrari G. Substance P modulation of human and murine corneal neovascularization. Invest Ophthalmol Vis Sci. 2018;59:1305–12. https://doi.org/10.1167/IOVS.17-23198.

    Article  CAS  PubMed  Google Scholar 

  13. Uusitalo H, Krootila K, Palkama A. Calcitonin gene-related peptide (CGRP) immunoreactive sensory nerves in the human and guinea pig uvea and cornea. Exp Eye Res. 1989;48:467–75. https://doi.org/10.1016/0014-4835(89)90030-4.

    Article  CAS  PubMed  Google Scholar 

  14. He J, Bazan HEP. Neuroanatomy and neurochemistry of mouse cornea. Invest Ophthalmol Vis Sci. 2016;57:664–74. https://doi.org/10.1167/iovs.15-18019.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Canning BJ, Chang AB, Bolser DC, Smith JA, Mazzone SB, McGarvey L. Anatomy and neurophysiology of cough: CHEST guideline and expert panel report. Chest. 2014;146:1633–48. https://doi.org/10.1378/chest.14-1481.

    Article  PubMed  Google Scholar 

  16. Zhang L, Sun T, Liu L, Wang L. The research of the possible mechanism and the treatment for capsaicin-induced cough. Pulm Pharmacol Ther. 2018;49:1–9. https://doi.org/10.1016/j.pupt.2017.12.008.

    Article  CAS  PubMed  Google Scholar 

  17. Miarons M, Tomsen N, Nascimento W, Espín L-F, Clavé P, et al. Increased levels of substance P in patients taking beta-blockers are linked with a protective effect on oropharyngeal dysphagia. Neurogastroenterol Motil. 2018;30:1–10. https://doi.org/10.1111/nmo.13397.

    Article  CAS  Google Scholar 

  18. Schröder JB, Marian T, Claus I, Muhle P, Pawlowski M, Wiendl H, et al. Substance P saliva reduction predicts pharyngeal dysphagia in Parkinson’s disease. Front Neurol. 2019;10:386. https://doi.org/10.3389/fneur.2019.00386.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Suntrup-Krueger S, Bittner S, Recker S, Meuth SG, Warnecke T, Suttrup I, et al. Electrical pharyngeal stimulation increases substance P level in saliva. Neurogastroenterol Motil. 2016;28:855–60. https://doi.org/10.1111/nmo.12783.

    Article  CAS  PubMed  Google Scholar 

  20. Nakato R, Manabe N, Shimizu S, Hanayama K, Shiotani A, Hata J, et al. Effects of capsaicin on older patients with oropharyngeal dysphagia: a double-blind, placebo-controlled, crossover study. Digestion. 2017;95:210–20. https://doi.org/10.1159/000463382.

    Article  CAS  PubMed  Google Scholar 

  21. Van Oosterhout WPJ, Schoonman GG, Garrelds IM, Danser AHJ, Chan KY, Terwindt GM, et al. A human capsaicin model to quantitatively assess salivary CGRP secretion. Cephalalgia. 2015;35:675–82. https://doi.org/10.1177/0333102414553824.

    Article  PubMed  Google Scholar 

  22. Ortega O, Rofes L, Martin A, Arreola V, López I, Clavé P. A comparative study between two sensory stimulation strategies after two weeks treatment on older patients with oropharyngeal dysphagia. Dysphagia. 2016;31:706–16. https://doi.org/10.1007/s00455-016-9736-4.

    Article  PubMed  Google Scholar 

  23. Tomsen N, Ortega O, Rofes L, Arreola V, Martin A, Mundet L, et al. Acute and subacute effects of oropharyngeal sensory stimulation with TRPV1 agonists in older patients with oropharyngeal dysphagia: a biomechanical and neurophysiological randomized pilot study. Therap Adv Gastroenterol. 2019;12:1–13. https://doi.org/10.1177/1756284819842043.

    Article  CAS  Google Scholar 

  24. Rofes L, Arreola V, Martin A, Clave P. Natural capsaicinoids improve swallow response in older patients with oropharyngeal dysphagia. Gut. 2013;62:1280–7. https://doi.org/10.1136/gutjnl-2011-300753.

    Article  PubMed  Google Scholar 

  25. Rofes L, Arreola V, Martin A, Clavé P. Effect of oral piperine on the swallow response of patients with oropharyngeal dysphagia. J Gastroenterol. 2014;49:1517–23. https://doi.org/10.1007/s00535-013-0920-0.

    Article  PubMed  Google Scholar 

  26. Alvarez-Berdugo D, Rofes L, Arreola V, Martin A, Molina L, Clavé P. A comparative study on the therapeutic effect of TRPV1, TRPA1, and TRPM8 agonists on swallowing dysfunction associated with aging and neurological diseases. Neurogastroenterol Motil. 2017. https://doi.org/10.1111/nmo.13185.

    Article  PubMed  Google Scholar 

  27. Tomsen N, Alvarez-Berdugo D, Rofes L, Ortega O, Arreola V, Nascimento W, et al. A randomized clinical trial on the acute therapeutic effect of TRPA1 and TRPM8 agonists in patients with oropharyngeal dysphagia. Neurogastroenterol Motil. 2020;32:e13821. https://doi.org/10.1111/nmo.13821.

    Article  CAS  PubMed  Google Scholar 

  28. Rosenbek JC, Robbins JA, Roecker EB, Coyle JL, Wood JL. A penetration-aspiration scale. Dysphagia. 1996;11:93–8. https://doi.org/10.1007/BF00417897.

    Article  CAS  PubMed  Google Scholar 

  29. Mahoney FI, Barthel DW. Functional evaluation: the Barthel index. Md State Med J. 1965;14:56–61.

    Google Scholar 

  30. Kaiser MJ, Bauer JM, Ramsch C, Uter W, Guigoz Y, Cederholm T, 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;13:782–8. https://doi.org/10.1007/s12603-009-0214-7.

    Article  CAS  PubMed  Google Scholar 

  31. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis Engl. 1987;40:373–83. https://doi.org/10.1016/0021-9681(87)90171-8.

    Article  CAS  Google Scholar 

  32. Niimi M, Hashimoto G, Hara T, Yamada N, Abo M, Fujigasaki H, et al. Relationship between frequency of spontaneous swallowing and salivary substance P level in patients with acute stroke. Dysphagia. 2018;33:414–8. https://doi.org/10.1007/s00455-017-9867-2.

    Article  PubMed  Google Scholar 

  33. Lorenzo I, Serra-Prat M, Carlos YJ. The role of water homeostasis in muscle function and frailty: a review. Nutrients. 2019;11:1–15. https://doi.org/10.3390/nu11081857.

    Article  CAS  Google Scholar 

  34. Mustafa KK, Muhammet CK, Gunes A, Basak B, Ozgur K, Hacer DV, et al. Association of bioelectrical impedance analysis-derived phase angle and sarcopenia in older adults. Nutr Clin Pract. 2017;32:103–9. https://doi.org/10.1177/0884533616664503.

    Article  Google Scholar 

  35. Yamada M, Kimura Y, Ishiyama D, Nishio N, Otobe Y, Tanaka, T, et al. Phase angle is a useful indicator for muscle function in older adults. J Nutr Health Aging. 2019;23:251–5. https://doi.org/10.1007/S12603-018-1151-0.

    Article  CAS  PubMed  Google Scholar 

  36. Armstrong LE. Assessing hydration status: the elusive gold standard. J Am Coll Nutr. 2007;26:575S-584S. https://doi.org/10.1080/07315724.2007.10719661.

    Article  PubMed  Google Scholar 

  37. Matsuo K, Balmer JB. Anatomy and physiology of feeding and swallowing—normal and abnormal. Phys Med Rehabil Clin N Am. 2008;19:691–707. https://doi.org/10.1016/j.pmr.2008.06.001.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Carrión S, Roca M, Costa A, Arreola V, Ortega O, Palomera E, et al. Nutritional status of older patients with oropharyngeal dysphagia in a chronic versus an acute clinical situation. Clin Nutr. 2017;36:1110–6. https://doi.org/10.1016/j.clnu.2016.07.009.

    Article  PubMed  Google Scholar 

  39. Wakabayashi H. Presbyphagia and sarcopenic dysphagia: association between aging, sarcopenia, and deglutition disorders. J Frailty Aging. 2014;3:97–103. https://doi.org/10.14283/jfa.2014.8.

    Article  CAS  PubMed  Google Scholar 

  40. Ortega O, Martín A, Clavé P. Diagnosis and management of oropharyngeal dysphagia among older persons, state of the art. J Am Med Dir Assoc. 2017;18:576–82. https://doi.org/10.1016/j.jamda.2017.02.015.

    Article  PubMed  Google Scholar 

  41. Carrión S, Costa A, Ortega O, Verin E, Clavé P, Laviano A. Complications of oropharyngeal dysphagia: malnutrition and aspiration pneumonia. In: Ekberg O, editor. Dysphagia diagnosis and treatment. Springer International Publishing AG; 2019. p. 823–57.

    Google Scholar 

  42. Ozer FF, Akın S, Soysal T, Gokcekuyu BM, Zararsız GE. Relationship between dysphagia and sarcopenia with comprehensive geriatric evaluation. Dysphagia. 2020. https://doi.org/10.1007/s00455-020-10120-3.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Jane Lewis for editing the English.

Funding

This study was supported by CIBERehd, Instituto de Salud Carlos III (EHD16PI02) and Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (PI18/00241).

Author information

Authors and Affiliations

  1. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas Y Digestivas (Ciberehd), Instituto de Salud Carlos III, Barcelona, Spain

    Noemí Tomsen, Omar Ortega & Pere Clavé

  2. Gastrointestinal Motility Laboratory, Department of Surgery, Hospital de Mataró, Consorci Sanitari del Maresme, Universitat Autònoma de Barcelona, Carretera de Cirera s/n 08304, Mataró, Spain

    Noemí Tomsen, Omar Ortega, Weslania Nascimento, Silvia Carrión & Pere Clavé

  3. Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain

    Noemí Tomsen

Authors
  1. Noemí Tomsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Omar Ortega
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Weslania Nascimento
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Silvia Carrión
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pere Clavé
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PC designed the research study. NT, OO and SC performed the research. WN performed and analyzed the VFS. NT analyzed the data. NT, OO and PC wrote the article. All the authors reviewed the article and approved the final version.

Corresponding author

Correspondence to Pere Clavé.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tomsen, N., Ortega, O., Nascimento, W. et al. Oropharyngeal Dysphagia in Older People is Associated with Reduced Pharyngeal Sensitivity and Low Substance P and CGRP Concentration in Saliva. Dysphagia 37, 48–57 (2022). https://doi.org/10.1007/s00455-021-10248-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00455-021-10248-w

Keywords

Search

Navigation