Current concepts in clinical and laboratory assessments of autonomic nervous system activity
More details
Hide details
Department of Pathophysiology, Jagiellonian University Collegium Medicum, Krakow, Poland
Corresponding author
Łukasz Dobrek   

Department of Pathophysiology, Jagiellonian University Collegium Medicum, Czysta 18, 31-121 Kraków, Poland
J Pre Clin Clin Res. 2015;9(1):63-68
Introduction and objective:
As the autonomic nervous system (ANS) dysfunction is present in course of many disorders, an objective assessment of the ANS function is very important. In practice, the assessment is difficult, and based rather on indirect analysis of autonomically-controlled cardiovascular reflexes, than on direct recording of activity of central or peripheral autonomic structures. The aim of our paper was to discuss briefly current, clinical and scientific ANS investigations, as well as possible future methods of autonomic activity evaluation.

A brief description of the state of knowledge:
The review presents a short outline of autonomic function assessments based on clinical autonomic tests (e.g. “Ewing’s battery”) and discusses the heart rate variability (HRV) study, as currently popular and widespread option of analysis of the ANS activity. Other, complementary methods, including the baroreceptor sensitivity testing, microneurography or plasma norepinephrine measurement were also mentioned. The article also provides premises related to the determination of selected neuropeptides in plasma or saliva as an innovative concept of autonomic activity assessment.

The available, clinical, non-invasive methods used for assessment of the ANS function are still relatively sparse and, in fact, a surrogate for direct ANS assessment. New methods of autonomic tension determination are still needed that would allow a more complete and reliable assessment. Reports of potential new laboratory markers of the ANS activity (NPY and VIP assay) bring some hope.

Mathias CJ. Autonomic diseases: clinical features and laboratory evaluation. J Neurol Neurosurg Psychiatry. 2003; 74(Suppl. III): 31–41.
Rydlewska A, Ponikowska B, Borodulin-Nadzieja L, Banasiak W, Jankowska EA, Ponikowski P. Ocena aktywności autonomicznego układu nerwowego związanej z odruchową regulacją układu sercowo-naczyniowego i oddychania. Kardiol Pol. 2010; 68(8): 951–957 (in Polish).
Zygmunt A, Stańczyk J. Methods of evaluation of autonomic nervous system function. Arch Med Sci. 2010; 6(1): 11–18.
Januszewicz W, Szczepańska-Sadowska E, Januszewicz A, Prejbisz A. Neurogenne aspekty nadciśnienia tętniczego. Nadciśn Tętn. 2008; 12(1): 1–11 (in Polish).
Mariańska K, Koszewicz M. Kliniczna ocean układu autonomicznego. Pol Przegl Neurol. 2008; 4(2): 51–57 (in Polish).
Suarez GA, Opfer-Gehrking KP, Offord MS, Atkinson EJ, O’Brien PC, Low PA. The autonomic Symptom Profile. A new instrument to assess autonomic symptoms. Neurology 1999; 52(3): 523–528.
Low PA. Clinical autonomic disorders: evaluation and management. 2nd ed. Lippincott-Raven Publishers, Philadelphia; 1997: 3–175.
Zakrzewska-Pniewska B. Autonomiczny układ nerwowy w cukrzycy. Aktualn Neurol. 2004; 4(2): 116–121 (in Polish).
Budrewicz S. Standardowe badania kliniczne czynności autonomicznych – układ przywspółczulny. In: Podemski R. (ed.). Diagnostyka autonomicznego układu nerwowego I zaburzeń snu. Ed. 1. Wrocław, Wydawnictwo Medyczne Urban & Partner; 2006: 5–22 (in Polish).
Budrewicz S. Standardowe badania kliniczne czynności autonomicznych – układ współczulny. In: Podemski R. (ed.). Diagnostyka autonomicznego układu nerwowego I zaburzeń snu. Ed. 1. Wrocław, Wydawnictwo Medyczne Urban & Partner; 2006; 23–33 (in Polish).
Ewing DJ. Cardiovascular reflexes and autonomic neuropathy. Clin Sci Mol Med. 1978; 55(4): 321–327.
Ewing DJ, Clarke BF. Diagnosis and management of diabetic autonomic neuropathy. Br Med J. 1982; 285(6346): 916–918.
Ewing DJ, Martyn CN, Young RJ, Clarke BF. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care 1985; 8(5): 491–498.
Malik M (ed.). Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology. Eur Heart J. 1996; 17(3): 354–381.
Berntson GG, Bigger JT JR, Eckberg DL, Grossman P, Kaufmann PG, Malik M, et al. Heart rate variability: origins, methods, and interpretive caveats. Psychophysiology 1997; 34(6): 623–648.
Sztajzel J. Heart rate variability: a noninvasive electrocardiographic method to measure the autonomic nervous system. Swiss Med Wkly. 2004; 134 (35–36): 514–522.
Acharya UR, Joseph KP, Kannathal N, Lim CM, Suri JS. Heart rate variability: a review. Med Bio Eng Comput. 2006; 44(12): 1031–1051.
Karim N, Hasan JA, Ali SS. Heart rate variability – a review. J Basic Appl Sci. 2011; 7(1): 71–77.
ChuDuc H, NguyenPhan K, NguyenViet DA. Review of Heart Rate Variability and its Applications. APCBEE Procedia 2013; 7: 80- 85.
Swenne CA. Baroreflex sensitivity: mechanisms and measurement. Neth Heart J. 2013; 21(2): 58–60.
La Rovere MT, Pinna GD, Raczak G. Baroreflex sensitivity: measurement and clinical implications. Ann Noninvasive Electrocardiol. 2008; 13(2): 191–207.
Gandevia SC, Hales JP. The methodology and scope of human microneurography. J Neurosci Methods. 1997; 74(2): 123–136.
Vallbo AB, Hagbarth KE, Wallin BG. Microneurography: how the technique developed and its role in the investigation of the sympathetic nervous system. J Appl Physiol. 2004; 96(4): 1262–1269.
Mano T, Iwase S, Toma S. Microneurography as a tool in clinical neuropsysiology to investigate peripheral neural traffic in humans. Clin Neurophysiol. 2006; 117(11): 2357–2384.
Wallin BG, Sundlof G, Eriksson BM, Dominiak P, Grobecker H, Lindblad LE. Plasma noradrenaline correlates to sympathetic muscle nerve activity in normotensive man. Acta Physiol Scand. 1981; 111(1): 69–73.
Goldstein DS, McCarty R, Polinsky RJ, Kopin IJ. Relationship between plasma norepinephrine and sympathetic neural activity. Hypertension 1983; 5(4): 552–559.
Sinski M, Lewandowski J, Abramczyk P, Narkiewicz K, Gaciong Z. Why study sympathetic nervous system? J Physiol Pharmacol. 2006; 57(Suppl. II): 79–92.
Esler M, Jennings G, Korner P, Willett I, Dudley F, Hasking G, et al. Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension 1988; 11(1): 3–20.
Esler M, Lambert G, Brunner-La Rocca HP, Vaddadi G, Kaye D. Sympathetic nerve activity and neurotransmitter release in humans: translation from pathophysiology into clinical practice. Acta Physiol Scand. 2003; 177(3): 275–284.
Lundberg JM, Terenius L, Hokfelt T, Martling CR, Tatemoto K, Mutt V, et al. Neuropeptide Y (NPY) – like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function. Acta Physiol Scand. 1982; 116(4): 477–480.
Lundberg JM, Franco-Cereceda A, Hemsen A, Lacroix JS, Pernow J. Pharmacology of noradrenaline and neuropeptide tyrosine (NPY)-mediated sympathetic cotransmission. Fundam Clin Pharmacol. 1990; 4(4): 373–391.
Burnstock G. Cotransmission in the autonomic nervous system. In: Buijs RM and Swaab DF, Eds. Handbook of Clinical Neurology. Autonomic Nervous System. Vol 117 (3rd series), Elsevier; 2013: 23–35.
Decressac M, Barker RA. Neuropeptide Y and its role in CNS disease and repair. Exp Neurol. 2012; 238(2): 265–272.
Heilig M. The NPY system in stress, anxiety and depression. Neuropeptides 2004; 38(4): 213–224.
Kuo LE, Zukowska Z. Stress, NPY and vascular remodeling: implications for stress-related diseases. Peptides 2007; 28(2): 435–440.
Pedrazzini T, Pralong F, Grouzmann E. Neuropeptide Y: the universal soldier. Cell Mol Life Sci. 2003; 60(2): 350–377.
Igarashi H, Fujimori N, Ito T, Nakamura T, Oono T, Nakamura K, et al. Vasoactive intestinal peptide (VIP) and VIP receptors – elucidation of structure and function for therapeutic applications. Int J Clin Med. 2011; 2(4): 500–508.
Petkó M, Ihionvien M. Distribution of substance P, vasoactive intestinal polypeptide and serotonin immunoreactive structures in the central nervous system of the lizard, Lacerta agilis. J Hirnforsch. 1989; 30(4): 415–423.
Costa M, Furness JB, Gibbins IL, Morris JL, Bornstein JC, Llewellyn-Smith IJ, et al. Colocalization of VIP with other neuropeptides and neurotransmitters in the autonomic nervous system. Ann N Y Acad Sci. 1988; 527: 103–109.
Culp DJ, Richardson LA. Regulation of mucous acinar exocrine secretion with age. J Dent Res. 1996; 75(1): 575–580.
El-Sayed ZA, Mostafa GA, Aly GS, El-Shahed GS, Abd El-Aziz MM, El-Emam SM. Cardiovascular autonomic function assessed by autonomic function tests and serum autonomic neuropeptides in Egyptian children and adolescents with rheumatic diseases. Rheumatology 2009; 48(7): 843–848.
Konttinen YT, Hukkanen M, Kemppinen P, Segerberg M, Sorsa T, Malmstrom M, et al. Peptide-containing nerves in labial salivary glands in Sjorgen’s syndrome. Arthritis Rheum. 1992; 35(7): 815–820.
Feher E, Zelles T, Nagy G. Immunocytochemical localization of neuropeptide-containing nerve fibres in human labial glands. Arch Oral Biol. 1999; 44(Suppl. 1): S33-S37.
Ekstrom J, Asztely A, Tobin G. Non-adrenergic, non-cholinergic influences on parotid acinar degranulation in response to stimulation of the parasympathetic innervation in the anaesthetized rat. Exp Physiol. 1996; 81(6): 935–942.
Proctor GB, Carpenter GH. Regulation of salivary gland function by autonomic nerves. Auton Neurosci. 2007; 133(1): 3–18.
Jensen JL, Brodin P, Berg T, Aars H. Parotid secretion of fluid, amylase and kallikrein during reflex stimulation under normal conditions and after acute administration of autonomic blocking agents in man. Acta Physiol Scand. 1991; 143(3): 321–329.
Dawidson I, Blom M, Lundeberg T, Theodorsson E, Angmar-Mansson B. Neuropeptides in the saliva of healthy subjects. Life Sci. 1997; 60(4–5): 269–278.
Naito T, Itoh H, Takeyama M. Effects of hange-koboku-to on neuropeptide levels in human plasma and saliva. Biol Pharm Bull. 2003; 26(11): 1609–1613.
Satoh Y, Itoh H, Takeyama M. Effects of bakumondoto on neuropeptide levels in human saliva and plasma. J Trad Med. 2009; 26(3): 122–130.
Humphrey SP, Williamson RT. A review of saliva: normal composition, flow and function. J Prosthet Dent. 2001; 85(2): 162–169.
Journals System - logo
Scroll to top