Research Interests

The research is supported by the German Research Foundation, the Federal Ministry of Education and Research, Grünenthal, and Pfizer

Joint Research of Wilfrid Jänig in Australia, Jerusalem, San Francisco and Japan

1990, 1991 Visiting Professor (6 months), Dept. of Physiology & Pharmacology, Univ. of Qld, St. Lucia, Australia, joint research with Prof. Elspeth McLachlan
1991 John Mayne Professorship, Dept. of Physiology & Pharmacology, Univ. of Qld, St. Lucia, Australia
1991 - 1997 Regular Visiting Professor (1 month per year), Dept. of Cell and Animal Biology, Institute of Life Sciences, Hebrew University, Jerusalem, Israel; joint research projects with Prof. Marshall Devor
1994 - 2008 Regular Visiting Professor (1 month per year), Prince of Wales Medical Research Institute, Randwick/Sydney, Australia; joint research projects with Prof. Elspeth McLachlan
1993 Max-Planck-Prize for the collaborative experimental work on the autonomic nervous system with Prof. Elspeth McLachlan
1993 - 1994 Presidential Chair in Medicine and Dentistry (Regent´s Professor), Univ. of California, San Francisco
1993 - 2002 Regular Visiting Professor (2-3 months per year), Dept. of Medicine, University of California, San Francisco; joint research with Prof. Jon Levine
2007 Myers Fellowship Howard Florey Institute, Melbourne; joint research with Prof. Robin McAllen
2010 Nagoya University, Dept. Neuroscience, joint research with Prof. Kazue Mizumura

 

I. Organization of the autonomic nervous system: cellular mechanisms and integration

The functioning of the autonomic nervous system has to be seen in the context of behavior, i.e. in the context of the somatomotor system, the neuroendocrine systems and the exteroceptive as well as interoceptive sensory systems.
 

1-ANS-Brain-Beh-NS-Fig1-2013.jpg


Functional organization of the nervous system to generate behavior. The motor system, consisting of the somatomotor, the autonomic (visceromotor) and the neuroendocrine system, controls behavior. It is hierarchically organized in spinal cord, brain stem and hypothalamus and receives three global types of synaptic input: (a) From the sensory systems monitoring processes in the body or in the environment to all levels of the motor system generating reflex behavior (reflex). (b) From the cerebral hemispheres responsible for cortical control of the behavior (cortical) based on neural processes related to cognitive and affective-emotional processes. (c) From the behavioral state system controlling attention, arousal, sleep/wakefulness, circadian timing etc. (state). The three general input systems communicate bidirectionally with each other (upper part of the figure). Integral components of behavior are sensations, affective-motivational processes and cognitive processes which are dependent on cortical activity. From Jänig The autonomic nervous system (2013) ref. 27 under teaching.

The research on the organization of the sympathetic nervous system in the periphery of the body and in the central nervous system, using neurophysiological, anatomical and other techniques, was one main research topic of the laboratory over the last 35 years. This systematic experimental work resulted into a general concept about the cellular organization and integrative functioning of the sympathetic nervous system. The essence of this concept is that this autonomic nervous system shows high anatomical and functional specificity, in its peripheral pathways and central circuits, with respect to the different types of autonomic target cells. This high specificity is the basis of all autonomic regulations (regulation of the cardiovascular system, body core temperature, gastrointestinal tract, pelvic evacuative organs, reproduction, protection of body tissues etc.). The collaborative work with Prof. Elspeth McLachlan (Sydney) and Prof. Robin McAllen (Melbourne) concentrated on this research interest.
 

2-ANS-Brain-Regul-NS-Fig15-2013.jpg


Reciprocal communication between brain and body tissues by efferent autonomic pathways and afferent pathways. The global autonomic centers in spinal cord, lower and upper brain and hypothalamus are shaded in violet. These centers consist of the neural circuits that are at the base of the homeostatic autonomic regulations and their co-ordination with the regulation of the neuroendocrine systems, the somatomotor systems and the sensory systems establishing behavior. The brain sends efferent commands to the peripheral target tissues through the peripheral autonomic pathways (red). The afferent pathways consist of groups of afferent neurons with unmyelinated or small diameter myelinated fibers (blue). These afferent neurons monitor the mechanical, thermal, chemical and metabolic states of the body tissues. From Jänig The autonomic nervous system (2013) ref. 27 under teaching.

The concept of functioning of the sympathetic nervous system was extended to the entire autonomic nervous system and culminated finally in the book
 

Wilfrid Jänig
The Integrative Action of the Autonomic Nervous System. Neurobiology of Homeostasis.
Cambridge University Press, Cambridge, 2006

 

3-Cover ANS Buch-06.jpg


which describes the neurobiology of the autonomic nervous system in the periphery of the body as well as in the central nervous system (see Introduction of the book, Link to Cambridge University Press).

The experimental work on the autonomic nervous system had recently two interesting extensions:
A. We have shown, in the rat, that vasoconstrictor pathways to skeletal muscle and skin are connected to in the spinal cord to very distinct inhibitory reflex circuits activated by nociceptive afferent neurons. Thus, activation of nociceptors in skeletal muscle or skin, e.g. by tissue injury, leads to increase of blood flow through skeletal muscle or skin via these spinal inhibitory reflex pathways. This neural mechanism of increasing blood flow through tissues furthers healing of injured tissues.
 

4-MS18-Fig9-color.jpg


Organization of the inhibitory nociceptive reflexes of the cutaneous vasoconstrictor (CVC) system (right, green) and of the muscle vasoconstrictor (MVC) system (left, blue): A hypothesis. Shown are transverse sections through the lumbar spinal cord L4-6 and L1-2. Nociceptive afferent neurons from skeletal muscle or skin of the rat hindlimb form synapses with second-order neurons in lamina I of L4-6 that project to L1-2. Stimulation of muscle nociceptive afferent neurons leads to inhibition of MVC neurons but not of CVC neurons. Stimulation of cutaneous nociceptive afferent neurons leads to inhibition of CVC neurons but not of MVC neurons. The inhibitory reflexes are organized at the level of the spinal cord, the inhibitory interneurons being possibly located in the same segments as the peganglionic neurons. The nociceptive inhibitory reflex systems to the CVC and the MVC pathway are separated. They are largely lateralized and under differential supraspinal control (red). BV, blood vessel. These inhibitory reflexes are also called Lovén Reflexes. From Kirillova-Woytke et al (2014).

B. The knowledge about the neurobiology of the peripheral and central autonomic nervous system was translated into principles underlying manual and osteopathic medicine. This translation led to the following book
 

King, H.H., Jänig, W., Patterson, M.M. (editors)
The Science and Clinical Application of Manual Medicine.
Churchill, Livingstone, Elsevier, Edinburgh, 2011


This book discusses the putative neurobiological basis underlying therapeutic manual interventions to treat functional diseases related to the musculo-skeletal system and visceral organs.
 

5-KingJaePat-2011-1.jpg


References (*review)

  1. Jänig, W., Häbler, H.-J. Organization of the autonomic nervous system: Structure and function. In Handbook of Clinical Neurology Vol. 74 (30)(ed. by Vinken, P.J., Bruyn, G.W.), The Autonomic Nervous System, Part I: Normal Functions (ed. by Appenzeller, O.), Chapter 1. Elsevier Science B.V., Amsterdam, pp. 1-52 (1999)*
  2. Jänig, W., Häbler, H.-J. Specificity in the organization of the autonomic nervous system: a basis for precise regulation of homeostatic and protective body functions. In Mayer, E.A., Saper, C.B. (eds.) The biological basis for mind body interaction". Prog. Brain Res. 122, 349-365 (2000)*
  3. Bartsch, T., Jänig, W., Häbler, H.-J., Reflex patterns in preganglionic sympathetic neurons projecting to the superior cervical ganglion in the rat. Autonomic Neurosci. 83, 66-74 (2000)
  4. Häbler, H.-J., Bartsch, T., Jänig, W. Respiratory rhythmicity in the activity of postganglionic neurones supplying the rat tail during hyperthermia. Autonomic Neurosci. 83, 75-80 (2000)
  5. Jänig, W. The autonomic nervous system and its co-ordination by the brain. In Handbook of Affective Sciences (ed. by Davidson, R.J., Scherer, K.R., Goldsmith, H.H.). Part II Autonomic Psychophysiology. Oxford University Press, New York, pp. 135 - 186 (2003)*
  6. Jänig, W., Häbler, H.-J. Neurophysiological analysis of target-related sympathetic pathways. From animal to human: similarities and differences. Acta Physiol. Scand. 177, 255-274 (2003)*
  7. Häbler, H.-J., Jänig, W. Reflexes in sympathetic vasoconstrictor neurones arising from urinary bladder afferents are not amplified early after inflammation in the anaesthetized cat. Pain 101, 251-257 (2003)
  8. Häbler, H.-J., Jänig, W. Reflexes in sympathetic vasoconstrictor neurones arising from urinary bladder afferents are not amplified early after inflammation in the anaesthetized cat. Pain 101, 251-257 (2003)
  9. Jänig, W. Non-nicotinic transmission in autonomic ganglia revisited – an important physiological function? J. Physiol. 566, 1-2 (2005)
  10. Jänig, W. Wie beeinflußt das Gehirn den Darm und der Darm das Gehirn? Forsch. Komplementärmed. 13, 245-246 (2006)*
  11. Jänig, W. The Integrative Action of the Autonomic Nervous System: Neurobiology of Homeostasis. Cambridge University Press, Cambridge, New York (2006)
  12. Jänig, W. Organization of the sympathetic nervous system: peripheral and central aspects. In: Rey, A.D., Chrousos, G., Besedovsky, H.O. (eds.) The Hypothalamus-Pituitary-Adrenal Axis. Neuroimmune Biology Vol. 7. Elsevier, Amsterdam, pp.55-85 (2008)*
  13. Jänig, W. Autonomic nervous system: Central control of the gastrointestinal tract. In Squire, L.R. (ed) Encyclopedia of Neuroscience. Vol 1. Academic Press, Oxford, pp. 871-881 (2009)*
  14. Jänig, W. Gastrointestinal tract role in neural control of metabolism, food intake, and body weight: a summary. In Squire, L.R. (ed.) Encyclopedia of Neuroscience. Vol 4. Academic Press, Oxford, pp. 583-586 (2009)*
  15. Jänig, W. Autonomic reflexes. In Binder MD, Hirokawa N, Windhorst U (eds.) Encyclopedia of Neuroscience, Springer, Berlin Heidelberg, pp 272-281 (2009)*
  16. Bratton, B., Davies, P., Jänig, W., McAllen, R. Ganglionic transmission in a vasomotor pathway studied in vivo. J Physiol 588, 1647-1659 (2010).
  17. King, H.H., Jänig, W., Patterson, M.M. (eds) The Science and Clinical Application of Manual Therapy. Elsevier, Amsterdam (2011)
  18. Jänig, W. Functions of the autonomic nervous system: Current concepts. In King, H.H., Jänig, W., Patterson, M.M. (eds.) The Science and Clinical Application of Manual Therapy: Elsevier, Amsterdam, pp. 15-53 (2011)*
  19. Jänig, W. Basic science on somato-visceral interactions: peripheral and central: evidence base and implications for research. In King, H.H., Jänig, W., Patterson, M.M. (eds.) The Science and Clinical Application of Manual Therapy: Elsevier, Amsterdam, pp. 275-300 (2011)*
  20. Jänig, W. Transmission of impulses in the parasympathetic cardiomotor pathway to the sino-atrial node. J. Physiol. 589, 5911-5913 (2011)
  21. Jänig, W. A never ending interesting and exciting story. J. Physiol. 590, 2537 (2012)
  22. Kirillova-Woytke, I., Baron, R., Jänig, W. Reflex inhibition of cutaneous sural and muscle vasoconstrictor neurons during stimulation of cutaneous and muscle nociceptors. J. Neurophysiol. 111, 1833-1845 (2014)
  23. Jänig, W. Editorial: Hyperalgesia, pain and stress. Eur. J.Pain 19, 471-472 (2015)
  24. Jänig, W. Letter: Thermosensors or not, this is the question. Temperature 2, 330-331 (2015)
  25. Jänig, W. Neurocardiology - a neurobiologist's perspective. J. Physio 1. 594, 3955-3962 (2016)

 

II. Neural mechanisms of visceral pain: physiology and pathophysiology

The topic peripheral mechanisms of visceral pain came into focus of the laboratory in the 1980s, in relation to the experimental work on the sympathetic nervous system (see Research Interest I). The laboratory concentrated on the question: What are the functionally characteristics of visceral nociceptors? This experimental work focusing then particularly on viscero-sympathetic reflexes.

References (*review)

  1. Jänig, W., Häbler, H.-J. Physiologie und Pathophysiologie viszeraler Schmerzen. Der Schmerz 16, 429-446 (2002)*
  2. Jänig, W. (ed.) Viszeraler Schmerz. Der Schmerz 16, 424 – 475 (2002)
  3. Jänig, W. Vagal afferents and visceral pain. In Undem, B., Weinreich, D. (eds.) Advances in Vagal Afferent Neurobiology. CRC Press, Boca Raton, pp. 461 - 489 (2005)*
  4. Jänig, W. Vagal afferent neurons and pain. In Basbaum, A.L., Bushnell M.C. (eds) Science of Pain. Academic Press, San Diego, pp. 245-252 (2009)*
  5. Jänig, W. Visceral pain – still an enigma? Pain 151, 239-240 (2010)
  6. Jänig, W. Neurobiologie viszeraler Schmerzen. Der Schmerz 28, 233-251 (2014)
  7. Jänig, W., Häuser, W. Viszerale Schmerzen – immer noch ein Stiefkind der Schmerzmedizin? Schmerztherapie – immer noch ein Stiefkind der Viszeralmedizin? Der Schmerz 28, 230-233 (2014)
  8. Elsenbruch, S, Häuser, W., Jänig, W. Viszeraler Schmerz. Der Schmerz 29, 496-502 (2015)

 

III. Neural mechanisms of neuropathic pain

Mechanical, metabolic or viral lesion of peripheral nerves may be followed by neuropathic pain. This pain is the consequence of dramatic plastic changes of the primary afferent neurons and secondary plastic changes in the central representation of the somatosensory systems leading to changed somatic sensations (including pain), reflexes and regulations. The laboratory concentrates on the functional changes, that occur in primary afferent neurons with myelinated or unmyelinated nerve fibers following nerve lesion, using neurophysiological techniques in vivo. Unraveling the peripheral mechanisms of neuropathic pain should lead to the design of molecular interventions that prevent the central and peripheral plastic changes to become irreversible with time and should lead to better treatment strategies of neuropathic pain. This research is conducted in collaboration with Prof. Ralf Baron (Department of Neurology, University of Kiel).
 

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Biochemical, anatomical and physiological changes of lesioned primary afferent neurons following nerve lesion and the subsequent central changes.The most dramatic changes occur in afferent neurons with unmyelinated fibers.

References (*review)

  1. Liu, X.-G., Eschenfelder, S., Blenk, K.H., Jänig, W., Häbler, H.-J. Spontaneous activity of axotomized afferent neurons after L5 spinal nerve injury in the rat. Pain 84, 309-318 (2000)
  2. Michaelis, M., Liu, X.-G., Jänig, W., Peripheral nerve lesion induces ongoing discharges originating from dorsal root ganglia in axotomized and unlesioned muscle afferents. J. Neurosci. 20, 2742-2748 (2000)
  3. Eschenfelder, S., Häbler, H.-J., Jänig, W. Dorsal root section elicits signs of neuropathic pain rather than reversing them in rats with L5 spinal nerve injury. Pain 87, 213-219 (2000)
  4. Häbler, H.-J., Eschenfelder, S., Liu, X.-G., Jänig, W. Sympathetic-sensory coupling after L5 spinal nerve lesion in the rat and its relation to changes in dorsal root ganglion blood flow. Pain 87, 335-345 (2000)
  5. Jänig, W., Häbler, H.-J., Sympathetic nervous system: contribution to chronic pain. Prog. Brain Res. 129, 453-470 (2000)*
  6. Gorodetskaya, N., Constantin, C., Jänig, W. Ectopic activity of cutaneous regenerating afferent nerve fibers following nerve lesion in the rat. Europ. J. Neurosci. 18, 1-11 (2003)
  7. Jänig, W. Mechanismen neuropathischer Schmerzen. Nervenheilkunde 23, 251 – 263 (2004)*
  8. Ludwig, J., Gorodetskaya, N., Schattschneider, J., Jänig, W., Baron, R.. Behavioral and sensory changes after direct ischemia-reperfusion injury in rats. Eur. J. Pain 11, 677-684 (2007)
  9. Jänig, W. What is the mechanism underlying treatment of pain by systemic application of lidocaine? Pain 137, 5-6 (2008)
  10. Grossmann, L.., Gorodetskaya, N., Teliban, A., Baron, R., Jänig W. Cutaneous afferent C-fibers regenerating along the distal stump after crush lesion show two types of cold-sensitivity. Eur. J. Pain 13:682-690 (2009).
  11. Jänig, W., Grossmann, L., Gorodetskaya, N. Mechano- and thermosensitivity of regenerating cutaneous nerve fibers. Exp Brain Res 196:101-114 (2009)
  12. Grossmann, L., Gorodetskaya, N., Baron, R. Jänig, W. Enhancement of spontaneous and evoked ectopic discharge in regenerating A- and C-fibers by inflammatory mediators. J. Neurophysiol. 101, 2762-2774 (2009)
  13. Gorodetskaya, N., Grossmann, L., Constantin, C., Jänig W. Functional properties of cutaneous A- and C-fibers 1-15 months after a nerve lesion. J. Neurophysiol. 102, 3129 - 3141 (2009)
  14. Teliban, A., Bartsch, F., Struck, M., Baron, R., Jänig, W. Axonal thermo- and mechanosensitivity of cutaneous afferent neurons. Eur. J. Neurosci 33, 110-118 (2011).
  15. Kirillova, I., Rausch, V.H., Tode, J., Baron, R., Jänig, W. Mechano- and thermosensitivity of injured muscle afferents. J. Neurophysiol. 105, 2058-2073 (2011).
  16. Kirillova, I., Teliban, A., Gorodetskaya, N., Grossmann, L., Bartsch, F., Rausch, V.H., Struck, M., Tode, J., Baron, R., Jänig, W. Responses of injured myelinated and unmyelinated afferent fibers to systemic or local lidocaine. Pain 152, 1562-1571 (2011)
  17. Jänig, W. Mechanical allodynia generated by stimulation of unmyelinated afferent nerve fibers. J. Physiol 589, 4407 – 4408 (2011)
  18. Jänig, W., Kirillova, I. (2012) Chronic nerve injury models. In: Handwerker, H.O., Arendt-Nielsen, L., (eds.) Models for Translation Pain Research. IASP Press Seattle, pp. 81-97 (2013)*
  19. Teliban, A., Bartsch, F., Struck, M., Baron, R., Jänig, W. Responses of intact and injured sural nerve fibers to cooling and menthol. J Neurophysiol. 111, 2071-2083 (2014).

 

IV. Sympathetic nervous system and pain

The (efferent) sympathetic nervous system may be involved, under pathophysiological conditions such as pain states following trauma with and without nerve lesion, in the generation of pain and other changes associated with the pain (see Research Interest VI). Pain depending on the activity in the sympathetic neurons is called sympathetically maintained pain (SMP). Research on the mechanisms underlying the coupling between sympathetic postganglionic neurons and afferent neurons under pathophysiological conditions was motivated by the clinical observations on patients with SMP and came into focus of the laboratory in the beginning of the 1980s. Over the years the laboratory made some important contributions to solve this enigmatic problem. Some of this research was conducted together with Prof. Marshall Devor (Jerusalem) and Prof. Elspeth McLachlan (Sydney).
 

7-Symp-aff.jpg


Plastic changes of the of the primary afferent neurons and sympathetic postganglionic neurons and the development of sympathetic-afferent coupling in the dorsal root ganglion and in the periphery following nerve lesion

References (*review)

  1. Häbler, H.-J., Eschenfelder, S., Liu, X.-G., Jänig, W. Sympathetic-sensory coupling after L5 spinal nerve lesion in the rat and its relation to changes in dorsal root ganglion blood flow. Pain 87, 335-345 (2000)
  2. Jänig, W., Häbler, H.-J., Sympathetic nervous system: contribution to chronic pain. Prog. Brain Res. 129, 453-470 (2000)*
  3. Jänig, W., Baron, R. The role of the sympathetic nervous system in neuropathic pain: clinical observations and animal models. In Hansson, P.T., Fields, H.L., Hill, R.G., Marchettini, P. (eds.) Neuropathic pain: pathophysiology and treatment. Progress in Pain Research and Management, Vol. 21. IASP Press, Seattle, pp. 125-149 (2001)*
  4. Jänig, W. Relationship between pain and autonomic phenomena in headache and other pain syndromes. Cephalalgia 23 (Suppl. 1), 43-48 (2003)*
  5. Jänig, W. Sympathetic nervous system and pain. Robertson, R., Biaggioni, I., Burnstock, G., Low, PA (eds.) Primer of the autonomic nervous system. 2nd edition, Elsevier Academic Press, Amsterdam, pp. 374-376 (2004)*
  6. Jänig, W. Autonomic nervous system and pain. In Basbaum, A.L., Bushnell, M.C. (eds.) Science of Pain. Academic Press, San Diego, pp. 193-225 (2009)*
  7. Jänig, W. Role of the sympathetic nervous system in the generation of pain. In Squire, L.R. (ed) Encyclopedia of Neuroscience. Vol 7. Academic Press, Oxford, pp. 371-383 (2009)*
  8. Jänig, W. Autonomic nervous system dysfunction. In Mayer, E.A., Bushnell, M.C. (eds.) Functional Pain Syndromes. IASP Press, Seattle, pp. 265-300 (2009)
  9. Baron, R., Jänig, W. Adrenergic and cholinergic targets in pain pharmacology. In Beaulieu, P., Lussier, D., Porreca, F., Dickinson, A.H. (eds.) Pharmacology of Pain. IASP Press, Seattle, pp. 347-381 (2010)*
  10. Jänig, W. Autonomic reactions in pain. Pain 153, 733-735 (2012)
  11. Jänig, W. (Field Editor) Pain and the Autonomic Nervous System. In Schmidt, R.F., Willis, W.D. (eds.) Encyclopedia of Pain. Springer, Berlin Heidelberg New York. 2nd edition Gebhart, G.F., Schmidt, R.F. (eds.), pp. 3753-3821 (2013)
  12. Jänig, W and Baron, R Sympathetic nervous system and pain. In Gebhart, G.F., Schmidt, R.F. (eds.) Encyclopedia of Pain. 2nd edition, Springer, Berlin, pp. 3763-3779 (2013)*
  13. Jänig, W., Häbler H-J.. Sympathetic nervous system in the generation of pain, animal behavioral models. In Gebhart, G.F., Schmidt, R.F. (eds.) Encyclopedia of Pain. 2nd edition, Springer, Berlin, pp. 3779-3784 (2013)
  14. Jänig W., Häbler, H.-J. Sympathetic-afferent coupling in the dorsal root ganglion, neurophysiological experiments. In Gebhart, G.F., Schmidt, R.F. (eds.) Encyclopedia of Pain. 2nd edition, Springer, Berlin, pp. 3794-33798 (2013)*
  15. Jänig W. Sympathoadrenal-system and mechanical hyperalgesic behaviour, animal experimentation. In Gebhart, G.F., Schmidt, R.F. (eds.) Encyclopedia of Pain. 2nd edition, Springer, Berlin, pp. 3816-3821 (2013)*
  16. Jänig, W. Pain, hyperalgesia and stress. Eur J Pain 19, 741-742 (2015)

 

V. Neuroendocrine and neural control of inflammation and hyperalgesia

Inflammation and sensitization of nociceptors (with subsequent hyperalgesia) following tissue lesions are reactions to protect the body against the invasion of bacteria and toxic substances and to further healing and recuperation. Both peripheral processes involve the immune system, the sympathetic nervous system and the hypothalamo-pituitary adrenal (HPA) system.
 

8-Jae-ANS-Inflamm-Fig4.jpg


Scheme for the feedback loops between spinal cord and brain stem on one side and the effector tissues involved in protective body reactions on the other side. Effector tissues (blood vessels, immune tissue, cells related to the immune system [IS], nociceptors) are modulated by the sympatho-neural, the sympatho-adrenal and the hypothalamo-pituitary-adrenal (HPA) systems. Function of the effector tissues are signaled by afferent neurons with unmyelinated (C-) or small-diameter myelinated (Aδ-) fibers and by signals from the immune system (endocrine/humoral signals) to spinal cord, brain stem and hypothalamus. The spinal neuronal circuits (“spinal programs”) are under supraspinal control (brain stem, hypothalamus). AC, adrenal cortex; AM, adrenal medulla. From Jänig & Green (2014).

Using experimental animal models of inflammation and mechanical hyperalgesia it has been shown that inflammation and sensitization of nociceptors are under the control of the brain via the sympathetic and the HPA system. Feedback from the peripheral inflamed tissue occurs via the nociceptive primary afferent neurons and signals from the immune system (cytokines). These findings argue that the brain is principally able to modulate inflammation and nociceptor sensitivity and to further healing and recuperation. These ideas, based on animal experimentation at the University of California San Francisco, have been developed by Wilfrid Jänig with Prof. Jon Levine.

References (*review)

  1. Jänig, W., Khasar, S.G., Levine, J.D., Miao, F.J.-P. The role of vagal visceral afferents in the control of nociception. In Mayer, E.A., Saper, C.B. (eds.) The biological basis for mind body interaction". Prog. Brain Res. 122, 271-285 (2000)*
  2. Miao, F.J.-P., Jänig, W., Levine, J.D. Nociceptive-neuroendocrine negative feedback control of neurogenic inflammation activated by capsaicin in the skin: role of the adrenal medulla. J. Physiol. 527, 601-610 (2000)
  3. Miao, F.J.-P., Jänig, W., Jasmin, L., Levine, J.D. Spino-bulbo-spinal pathway mediating vagal modulation of nociceptive-neuroendocrine control of inflammation in the rat. J. Physiol. 532, 811-922 (2001)
  4. Miao, F.J.-P., Jänig, W., Jasmin, L., Levine, J.D. Blockade of nociceptive inhibition of plasma extravasation by opioid stimulation of the periaqueductal gray and its interaction with vagus-induced inhibition in the rat. Neuroscience 119, 875-885 (2003)
  5. Straub, R.H., Baerwald, C., Jänig, W., Wahle, M. Autonomic dysfunction in rheumatic diseases. Rheum. Dis. Clin. North Am. 31, 61 – 75 (2005)*
  6. Green PG, Jänig W. Sympathetic postganglionic neurons in neurogenic inflammation of the synovia. In Gebhart, G.F., Schmidt, R.F. (eds.) Encyclopedia of Pain. 2nd edition, Springer, Berlin, pp. 3784-3789 (2013)*
  7. Jänig, W. (ed.) Autonomic nervous system and inflammation. Autonomic Neuroscience: Basic and Clinical 1-117 (2014)
  8. Jänig, W. Editorial: Autonomic nervous system and inflammation. Autonomic Neuroscience: Basic and Clinical 182, 1-3 (2014)
  9. Jänig, W. Autonomic nervous system and inflammation: a conceptual view. Autonomic Neuroscience. Basic and Clinical 182, 4-14 (2014)*
  10. Jänig, W., Green, P.G. Acute inflammation in the joint: role of the sympathetic nervous system and control by the brain. Autonomic Neuroscience. Basic and Clinical 182, 42-54 (2014)*

 

VI. Mechanisms underlying Complex Regional Pain Syndromes (CRPS) and similar pain diseases

Based on clinical observations and animal experimentation Ralf Baron (Prof. of Neurology, Kiel) and Wilfrid Jänig developed the idea and formulated the concept that the complex regional pain syndrome (CRPS) is a disease of the central nervous system involving the somatosensory systems, the sympathetic nervous system and the somatomotor system. This conceptual view, that is based on the translation of experimentation on animal models and on patients with CRPS as experimental human model into clinical reality, will much better explain the clinical phenomenology of CRPS and will lead to a better formulation of hypotheses that can be tested experimentally. Our scientific view to explain CRPS mechanistically may serve as a model to explore other generalized chronic pain diseases such as irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, non-ulcer dyspepsia, tension-type headache, chronic pelvic pain, chronic low back pain and the like.
 

9-JaeBa-CRPS-Concept-2.jpg


Schematic diagram summarizing the sensory, autonomic and somatomotor changes in complex regional pain syndrome I (CRPS I) patients. The figure symbolizes the CNS (forebrain, brain stem and spinal cord). Changes occur in the central representations of the somatosensory, the motor and the sympathetic nervous system (which include the spinal circuits) and are reflected in the changes of the sensory painful and non-painful perceptions, of cutaneous blood flow and sweating, of peripheral tissues (edema, inflammation, trophic) and of motor performances. They are triggered and possibly maintained by the nociceptive afferent input from the somatic and visceral body domains. It is unclear whether these central changes are reversible in chronic CRPS I patients. The central changes may include changes of the endogenous control system of nociceptive impulse transmission. Coupling between the sympathetic neurons and the afferent neurons in the periphery (see red arrow) is one component of the pain in CRPS I patients with sympathetically-maintained pain (SMP). However, it seems to be unimportant in CRPS I patients without SMP. From Jänig and Baron (2002, 2003)

References (*review)

  1. Jänig, W., Stanton-Hicks, M. (eds.) Reflex sympathetic dystrophy - a reappraisal. Progress in Pain Research and Management, Vol. 6. IASP Press, Seattle (1996)
  2. Rommel, O., Gehling, M., Dertwinkel, R., Witscher, K., Zenz, M., Malim, J.P., Jänig, W. Hemisensory impairment in patients with complex regional pain syndrome. Pain 80, 95-111 (1999)
  3. Harden, R.N., Baron, R. Jänig, W. (eds.) Complex regional pain syndrome. Progress in Pain Research and Management, Vol. 22. IASP Press, Seattle (2001)
  4. Friberg, L., Sandrini, G., Jänig, W., Jensen, R., Russell, D., Sand, T., Schoenen, J., van Buchem, M., van Dijk, J.G. Clinical and para-clinical tests in routine examination of headache patients. Funct. Neurol. 15, 82-85 (2000)
  5. Rommel, O., Malin, J.-P., Zenz, M., Jänig, W. Quantitative sensory testing, neurophysiological and psychological examination in patients with complex regional pain syndrome and hemisensory deficits. Pain 93, 279-293 (2001)
  6. Jänig, W., Baron, R. Complex regional pain syndrome is a disease of the central nervous system. Clin. Auton. Res. 12, 150-164 (2002)*
  7. Baron, R., Fields, H., Jänig, W., Kitt, C., Levine, J.D. Reflex Sympathetic Dystrophy/ Complex Regional Pain Syndromes (CRPS): State-of-the-Science. Anaesthesia and Analgesia 95, 1812-1816 (2002)
  8. Friberg, L., Sandrini, G., Jänig, W., Jensen, R., Russell, D., Sanchez del Rio, M., Sand, T., Schoenen, J., van Buchem, M., van Dijk, J.G. Instrumental investigations in primary headache. An updated review and new perspectives. Funct. Neurol.18, 127-144 (2003)*
  9. Jänig, W., Baron, R. Complex regional pain syndrome: mystery explained? Lancet Neurology 2, 687-697 (2003)*
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  19. Jänig, W., Schaumann, R., Vogt, W. (eds) CRPS. Complex regional pain syndrome. SUVA, Luzern (2013)
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Wilfrid Jänig