Advertisement

Sympathetic nervous system and inflammation: A conceptual view

Published:February 12, 2014DOI:https://doi.org/10.1016/j.autneu.2014.01.004

      Abstract

      The peripheral sympathetic nervous system is organized into function-specific pathways that transmit the activity from the central nervous system to its target tissues. The transmission of the impulse activity in the sympathetic ganglia and to the effector tissues is target cell specific and guarantees that the centrally generated command is faithfully transmitted. This is the neurobiological basis of autonomic regulations in which the sympathetic nervous system is involved. Each sympathetic pathway is connected to distinct central circuits in the spinal cord, lower and upper brain stem and hypothalamus. In addition to its conventional functions, the sympathetic nervous system is involved in protection of body tissues against challenges arising from the environment as well as from within the body. This function includes the modulation of inflammation, nociceptors and above all the immune system. Primary and secondary lymphoid organs are innervated by sympathetic postganglionic neurons and processes in the immune tissue are modulated by activity in these sympathetic neurons via adrenoceptors in the membranes of the immune cells (see Bellinger and Lorton, 2014). Are the primary and secondary lymphoid organs innervated by a functionally specific sympathetic pathway that is responsible for the modulation of the functioning of the immune tissue by the brain? Or is this modulation of immune functions a general function of the sympathetic nervous system independent of its specific functions? Which central circuits are involved in the neural regulation of the immune system in the context of neural regulation of body protection? What is the function of the sympatho-adrenal system, involving epinephrine, in the modulation of immune functions?

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Autonomic Neuroscience: Basic and Clinical
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. Ader A. Psychoneuroimmunology. Fourth ed. Academic Press Elsevier, Amsterdam2007
        • Ader A.
        • Cohen N.
        Psychoneuroendocrinology: conditioning and stress.
        Annu. Rev. Physiol. 1993; 44: 53-85
        • Arck P.
        • Paus R.
        From the brain–skin connection: the neuroendocrine–immune misalliance of stress itch.
        Neuroimmunomodulation. 2006; 13: 347-356
        • Arck P.C.
        • Slominski A.
        • Theoharides T.C.
        • Peters E.M.
        • Paus R.
        Neuroimmunology of stress: skin takes center stage.
        J. Invest. Dermatol. 2006; 126: 1697-1704
        • Bandler R.
        • Keay K.A.
        Columnar organization in the midbrain periaqueductal gray and the integration of emotional expression.
        Prog. Brain Res. 1996; 107: 285-300
        • Bandler R.
        • Shipley M.T.
        Columnar organization in the midbrain periaqueductal gray: modules for emotional expression?.
        Trends Neurosci. 1994; 17: 379-389
        • Bandler R.
        • Carrive P.
        • Zhang S.P.
        Integration of somatic and autonomic reactions within the midbrain periaqueductal grey: viscerotopic, somatotopic and functional organization.
        Prog. Brain Res. 1991; 87: 269-305
        • Bandler R.
        • Price J.L.
        • Keay K.A.
        Brain mediation of active and passive emotional coping.
        Prog. Brain Res. 2000; 122: 333-349
        • Baron R.
        • Jänig W.
        Sympathetic and afferent neurons projecting in the splenic nerve of the cat.
        Neurosci. Lett. 1988; 94: 109-113
        • Bellinger D.L.
        • Lorton D.
        Autonomic regulation of cellular immune function.
        Auton. Neurosci. Basic Clin. 2014; 182 (this Special Issue of Autonomic Neuroscience): 15-41
        • Bellinger D.L.
        • Nance D.M.
        • Lorton D.
        Innervation of the immune system.
        in: Kusnecow A.W. Anisman H. The Wiley-Blackwell Handbook of Psychoneuroimmunology. John Wiley & Sons Ltd., 2013: 24-49
        • Besedovsky H.O.
        • del Rey A.
        Immune–neuroendocrine circuits: integrative role of cytokines.
        Front. Neuroendocrinol. 1992; 13: 61-94
        • Besedovsky H.O.
        • del Rey A.
        Immune–neuroendocrine interactions: facts and hypotheses.
        Endocr. Rev. 1995; 17: 64-102
        • Bienenstock J.
        • McDermott M.R.
        Bronchus- and nasal-associated lymphoid tissues.
        Immunol. Rev. 2005; 206: 22-31
        • Birder L.
        Urinary bladder, cystitis and nerve/urothelial interactions.
        Auton. Neurosci. Basic Clin. 2014; 182 (this Special Issue of Autonomic Neuroscience): 89-94
        • Bos J.D.
        • Luiten R.M.
        Skin immune system.
        Cancer Treat. Res. 2009; 146: 45-62
        • Bratton B.
        • Davies P.
        • Jänig W.
        • McAllen R.
        Ganglionic transmission in a vasomotor pathway studied in vivo.
        J. Physiol. Lond. 2010; 588: 1647-1659
        • Buske-Kirschbaum A.
        Endocrine and immune responses to stress in chronic inflammatory skin disorder (atopic dermatitis).
        in: Ader R. Psychoneuroimmunology. Fourth ed.II. Academic Press Elsevier, Amsterdam2007: 975-991
        • Cervi A.L.
        • Lukewich M.K.
        • Lomax A.E.
        Role of enteric transmission in host defense and protection of the gastrointestinal tract.
        Auton. Neurosci. Basic Clin. 2014; (this Special Issue of Autonomic Neuroscience)
        • Clark R.A.
        • Chong B.
        • Mirchandani N.
        • Brinster N.K.
        • Yamanaka K.
        • Dowgiert R.K.
        • Kupper T.S.
        The vast majority of CLA+ T cells are resident in normal skin.
        J. Immunol. 2006; 176: 4431-4439
        • Dantzer R.
        • Bluthé R.-M.
        • Castanon N.
        • Kelley K.W.
        • Konsman J.-P.
        • Laye S.
        • Lestage J.
        • Parnet P.
        Cytokines, sickness behavior, and depression.
        in: Ader R. Psychoneuroimmunology. Fourth ed. I. Academic Press Elsevier, Amsterdam2007: 281-318
        • Denton K.M.
        • Luff S.E.
        • Shweta A.
        • Anderson W.P.
        Differential neural control of glomerular ultrafiltration.
        Clin. Exp. Pharmacol. Physiol. 2004; 31: 380-386
        • DiBona G.F.
        • Kopp U.C.
        Neural control of renal function.
        Physiol. Rev. 1997; 77: 75-197
        • Edwards F.R.
        • Hirst G.D.S.
        • Klemm M.F.
        • Steele P.A.
        Different types of ganglion cell in the cardiac plexus of guinea-pigs.
        J. Physiol. Lond. 1995; 486: 453-471
        • Esler M.
        • Jennings G.
        • Lambert G.
        • Meredith I.
        • Horne M.
        • Eisenhofer G.
        Overflow of catecholamine neurotransmitters to the circulation: source, fate, and functions.
        Physiol. Rev. 1990; 70: 963-985
        • Felten D.L.
        • Felten S.Y.
        • Carlson S.L.
        • Olschowka J.A.
        • Livnat
        Noradrenergic and peptidergic innervation of lymphoid tissue.
        J. Immunol. 1985; 135: 755s-765s
        • Felten D.L.
        • Felten S.Y.
        • Bellinger D.L.
        • Carlson S.L.
        • Ackerman K.D.
        • Madden K.S.
        • Olschowki J.A.
        • Livnat S.
        Noradrenergic sympathetic neural interactions with the immune system: structure and function.
        Immunol. Rev. 1987; 100: 225-260
        • Furness J.B.
        The Enteric Nervous System.
        Blackwell Science Ltd., Oxford2006
        • Furness J.B.
        • Morris J.L.
        • Gibbins I.L.
        • Costa M.
        Chemical coding of neurons and plurichemical transmission.
        Annu. Rev. Pharmacol. Toxicol. 1989; 29: 289-306
        • Garland E.M.
        Dopamine beta-hydroxylase deficiency.
        in: Robertson D. Biaggioni I. Burnstock G. Low P.A. Paton J.F.R. Primer in the Autonomic Nervous System. Second ed. Academic Press Elsevier, San Diego Amsterdam2012: 431-434
        • Gibbins I.L.
        Chemical neuroanatomy of sympathetic ganglia.
        in: McLachlan E.M. Autonomic Ganglia. Harwood Academic Publishers, Luxembourg1995: 73-122
        • Gibbins I.L.
        Peripheral autonomic pathways.
        in: Paxinos G. Mai J.K. The Human Nervous System. Second ed. Elsevier Academic Press, Amsterdam San Diego London2004: 134-189
        • Grogan J.L.
        • Ouyang W.
        A role for Th17 cells in the regulation of tertiary lymphoid follicles.
        Eur. J. Immunol. 2012; 42: 2255-2262
        • Hirst G.D.S.
        • Bramich N.J.
        • Edwards F.R.
        • Klemm M.
        Transmission at autonomic neuroeffector junctions.
        Trends Neurosci. 1992; 15: 40-46
        • Hirst G.D.S.
        • Choate J.K.
        • Cousins H.M.
        • Edwards F.R.
        • Klemm M.F.
        Transmission by post-ganglionic axons of the autonomic nervous system: the importance of the specialized neuroeffector junction.
        Neuroscience. 1996; 73: 7-23
      2. Holmgren S. Olsson C. Comparative physiology of the autonomic nervous system. Auton. Neurosci.165. 2011: 1-148
        • Hori T.
        • Katafuchi T.
        • Take S.
        • Shimizu N.
        • Niijima A.
        The autonomic nervous system as a communication channel between the brain and the immune system.
        Neuroimmunomodulation. 1995; 2: 203-215
        • Jänig W.
        Organization of the lumbar sympathetic outflow to skeletal muscle and skin of the cat hindlimb and tail.
        Rev. Physiol. Biochem. Pharmacol. 1985; 102: 119-213
        • Jänig W.
        The integrative action of the autonomic nervous system.
        Neurobiology of Homeostasis. Cambridge University Press, Cambridge, New York2006
        • Jänig W.
        Autonomic nervous system and pain.
        in: Basbaum A.I. Bushnell M.C. Science of Pain. Academic Press, San Diego2009: 193-225
        • Jänig W.
        Autonomic nervous system dysfunction.
        in: Mayer E.A. Bushnell M.C. Functional Pain Syndromes. IASP Press, Seattle2009: 265-300
        • Jänig W.
        Transmission of impulses in the parasympathetic cardiomotor pathway to the sino-atrial node.
        J. Physiol. Lond. 2011; 589: 5911-5913
        • Jänig W.
        Pain and the sympathetic nervous system: pathophysiological mechanisms.
        in: Mathias C.J. Bannister R. Autonomic Failure. Fifth ed. Oxford University Press, New York Oxford2013: 236-246
        • Jänig W.
        The autonomic nervous system.
        in: Galizia C.G. Lledo P.-M. Neurosciences. From Molecule to Behavior: A University Textbook. Springer Spectrum Springer-Verlag, Berlin Heidelberg2013: 179-211
        • Jänig W.
        • Green P.G.
        Acute inflammation in the joint: role of the sympathetic nervous system and control by the brain involving neuroendocrine systems.
        Auton. Neurosci. Basic Clin. 2014; 182 (this Special Issue of Autonomic Neuroscience): 42-54
        • Jänig W.
        • Häbler H.J.
        Neurophysiological analysis of target-related sympathetic pathways—from animal to human: similarities and differences.
        Acta Physiol. Scand. 2003; 177: 255-274
        • Jänig W.
        • Levine J.D.
        Autonomic–neuroendocrine–immune responses in acute and chronic pain.
        in: McMahon S.B. Koltzenburg M. Tracey I. Turk D. Wall & Melzack's Textbook of Pain. Sixth ed. Elsevier Churchill Livingstone, Edinburgh2013: 205-218
        • Jänig W.
        • McLachlan E.M.
        Organization of lumbar spinal outflow to distal colon and pelvic organs.
        Physiol. Rev. 1987; 67: 1332-1404
        • Jänig W.
        • McLachlan E.M.
        Neurobiology of the autonomic nervous system.
        in: Mathis C.J. Bannister R. Autonomic Failure. Fifth ed. Oxford University Press, New York Oxford2013: 21-34
        • Jänig W.
        • Khasar S.G.
        • Levine J.D.
        • Miao F.J.
        The role of vagal visceral afferents in the control of nociception.
        Prog. Brain Res. 2000; 122: 273-287
        • Katafuchi T.
        • Ichijo T.
        • Take S.
        • Hori T.
        Hypothalamic modulation of splenic natural killer cell activity in rats.
        J. Physiol. Lond. 1993; 471: 209-221
        • Katafuchi T.
        • Take S.
        • Hori T.
        Roles of sympathetic nervous system in the suppression of cytotoxicity of splenic natural killer cells in the rat.
        J. Physiol. Lond. 1993; 465: 343-357
        • Kaufmann H.
        • Schatz I.J.
        Pure autonomic failure.
        in: Robertson D. Biaggioni I. Burnstock G. Paton J.F.R. Primer in the Autonomic Nervous System. Second ed. Academic Press Elsevier, San Diego Amsterdam2012: 467-469
        • Keast J.R.
        • Luckensmeyer G.B.
        • Schemann M.
        All pelvic neurons in male rats contain immunoreactivity for the synthetic enzymes of either noradrenaline or acetylcholine.
        Neurosci. Lett. 1995; 196: 209-212
        • Khasar S.G.
        • Miao F.J.-P.
        • Jänig W.
        • Levine J.D.
        Modulation of bradykinin-induced mechanical hyperalgesia in the rat by activity in abdominal vagal afferents.
        Eur. J. Neurosci. 1998; 10: 435-444
        • Khasar S.G.
        • Miao F.J.-P.
        • Jänig W.
        • Levine J.D.
        Vagotomy-induced enhancement of mechanical hyperalgesia in the rat is sympathoadrenal-mediated.
        J. Neurosci. 1998; 18: 3043-3049
        • Khasar S.G.
        • Green P.G.
        • Miao F.J.-P.
        • Levine J.D.
        Vagal modulation of nociception is mediated by adrenomedullary epinephrine in the rat.
        Eur. J. Neurosci. 2003; 17: 909-915
        • Kopp U.C.
        • DiBona G.F.
        The neural control of renal function. In the kidney: physiology and pathophysiology.
        in: Seldin G. Giebisch G. Raven Press, New York2000: 981-1006
        • Kupper T.S.
        T cells, immunosurveillance, and cutaneous immunity.
        J. Dermatol. Sci. 2000; 24: S41-S45
        • Kupper T.S.
        • Fuhlbrigge R.C.
        Immune surveillance in the skin: mechanisms and clinical consequences.
        Nat. Rev. Immunol. 2004; 4: 211-222
        • Langley J.N.
        The autonomic nervous system. Part I.
        W. Heffer, Cambridge1921
      3. Llewellyn-Smith I.J. Verbene A.J.M. Central Regulation of Autonomic Functions. Oxford University Press, New York2011
        • Luff S.E.
        • Hengstberger S.G.
        • McLachlan E.M.
        • Anderson W.P.
        Distribution of sympathetic neuroeffector junctions in the juxtaglomerular region of the rabbit kidney.
        J. Auton. Nerv. Syst. 1992; 40: 239-253
        • Madden K.S.
        • Felten D.L.
        Experimental basis for neural–immune interactions.
        Physiol. Rev. 1995; 75: 77-106
        • Madden K.S.
        • Sanders K.
        • Felten D.L.
        Catecholamine influences and sympathetic modulation of immune responsiveness.
        Rev. Pharmacol. Toxicol. 1995; 35: 417-448
        • Maier S.F.
        • Watkins L.R.
        Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition.
        Psychol. Rev. 1998; 105: 83-107
      4. Mathias C.J. Bannister R. Autonomic Failure. Fifth ed. Oxford University Press, New York Oxford2013
        • Mathias C.J.
        • Low D.A.
        • Iodice V.
        • Bannister R.
        Investigation of autonomic disorders.
        in: Mathias C.J. Bannister R. Autonomic Failure. Fifth ed. Oxford University Press, Oxford2013: 259-289
        • McGovern A.
        • Mazzone S.
        Neural regulation of inflammation in the airways and lungs.
        Auton. Neurosci. Basic Clin. 2014; 182 (this Special Issue of Autonomic Neuroscience): 95-101
        • McLachlan E.M.
        Autonomic ganglia. In:.
        in: The Autonomic Nervous System (edited by Burnstock, G.). vol. 6. Harwood Academic Publishers, Luxembourg1995
        • Martelli D.
        • McKinley M.J.
        • McAllen R.M.
        The cholinergic anti-inflammatory pathway: a critical review.
        Auton. Neurosci, Basic Clin2014 (this Special Issue of Autonomic Neuroscience)
        • McLachlan E.M.
        • Hu P.
        Inflammation in the dorsal root ganglion after injury: effects of the sympathetic supply.
        Auton. Neurosci. Basic Clin. 2014; 182 (this Special Issue of Autonomic Neuroscience): 55-64
        • McLachlan E.M.
        • Davies P.J.
        • Häbler H.J.
        • Jamieson J.
        On-going and reflex synaptic events in rat superior cervical ganglion cells.
        J. Physiol. Lond. 1997; 501: 165-181
        • McLachlan E.M.
        • Häbler H.J.
        • Jamieson J.
        • Davies P.J.
        Analysis of the periodicity of synaptic events in neurones in the superior cervical ganglion of anaesthetized rats.
        J. Physiol. Lond. 1998; 511: 461-478
        • Meckler R.L.
        • Weaver L.C.
        Characteristics of ongoing and reflex discharge of single splenic and renal sympathetic postganglionic fibres in cats.
        J. Physiol. Lond. 1988; 396: 139-153
        • Morris J.L.
        • Gibbins I.L.
        Co-transmission and neuromodulation.
        in: Burnstock G. Hoyle C.H.V. Autonomic Neuroeffector Mechanisms. Harwood Academic Publishers Chur, 1992: 33-119
        • Morrison S.F.
        RVLM and raphe differentially regulate sympathetic outflows to splanchnic and brown adipose tissue.
        Am. J. Physiol. 1999; 276: R962-R973
        • Morrison S.F.
        Differential control of sympathetic outflow.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2001; 281: R683-R698
        • Morrison S.F.
        • Cao W.H.
        Different adrenal sympathetic preganglionic neurons regulate epinephrine and norepinephrine secretion.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000; 279: R1763-R1775
        • Nance D.M.
        • Sanders V.M.
        Autonomic innervation and regulation of the immune system (1987–2007).
        Brain Behav. Immun. 2007; 21: 736-745
        • Neyt K.
        • Perros F.
        • Geurts van Kessel C.H.
        • Hammad H.
        • Lambrecht B.N.
        Tertiary lymphoid organs in infection and autoimmunity.
        Trends Immunol. 2012; 33: 297-305
        • Okamoto S.
        • Ibaraki K.
        • Hayashi S.
        • Saito M.
        Ventromedial hypothalamus suppresses splenic lymphocyte activity through sympathetic innervation.
        Brain Res. 1996; 739: 308-313
        • Peters E.M.
        • Liezmann C.
        • Klapp B.F.
        • Kruse J.
        The neuroimmune connection interferes with tissue regeneration and chronic inflammatory disease in the skin.
        Ann. N. Y. Acad. Sci. 2012; 1262: 118-126
      5. Robertson D. Biaggioni I. Burnstock G. Low P.A. Paton J.F.R. Primer on the Autonomic Nervous System. Second ed. Academic Press Elsevier, Boston Amsterdam2012
        • Saphier D.
        Psychoimmunology: the missing link.
        in: Schulkin J. Hormonally Induced Changes in Mind and Brain. Academic Press, 1993: 191-224
        • Schaible H.-G.
        • Straub R.
        Function of the sympathetic supply in acute and chronic experimental joint inflammation.
        Auton. Neurosci. Basic Clin. 2014; (this Special Issue of Autonomic Neuroscience)
        • Schlereth T.
        • Drummond P.
        • Birklein F.
        Inflammation in CRPS: role of the sympathetic supply.
        Auton. Neurosci, Basic Clin.2014 (this Special Issue of Autonomic Neuroscience)
      6. Schedlowski M. Tewes U. Psychoneuroimmunology. An Interdisciplinary Introduction. Kluwer Academic Plenum Publishers, New York, Boston1999
        • Sharkey K.
        • Savidge T.
        Role of enteric transmission in host defense and protection of the gastrointestinal tract.
        Auton. Neurosci. Basic Clin. 2014; 181 (this Special Issue of Autonomic Neuroscience): 94-106
        • Stein R.D.
        • Weaver L.C.
        Multi- and single-fibre mesenteric and renal sympathetic responses to chemical stimulation of intestinal receptors in cats.
        J. Physiol. Lond. 1988; 396: 155-172
        • Swanson L.W.
        Cerebral hemisphere regulation of motivated behavior.
        Brain Res. 2000; 886: 113-164
        • Swanson L.W.
        Basic plan of the nervous system.
        in: Squire L.R. Bloom F.E. Spitzer N.C. du Lac S. Ghosh A. Berg D. Fundamental Neuroscience. Third ed. Academic Press, San Diego2008: 15-40
        • van de Pavert S.A.
        • Mebius R.E.
        New insights into the development of lymphoid tissues.
        Nat. Rev. Immunol. 2010; 10: 664-674
        • Verberne A.J.
        • Sartor D.M.
        Rostroventrolateral medullary neurons modulate glucose homeostasis in the rat.
        Am. J. Physiol. Endocrinol. Metab. 2010; 299: E802-E807
        • Vollmer R.R.
        • Meyers-Schoy S.A.
        • Kolibal-Pegher S.S.
        • Edwards D.J.
        The role of the adrenal medulla in neural control of blood pressure in rats.
        Clin. Exp. Hypertens. 1995; 17: 649-667
        • Wallin B.G.
        Intraneural recordings of normal and abnormal sympathetic activity in humans.
        in: Mathias C.J. Bannister R. Autonomic Failure. Fifth ed. Oxford University Press, New York, Oxford2013: 323-331
        • Williams I.R.
        • Kupper T.S.
        Immunity at the surface: homeostatic mechanisms of the skin immune system.
        Life Sci. 1996; 58: 1485-1507