Zusammenfassung
Neurogene Entzündungen werden hervorgerufen durch Aktivierung unmyelinisierter sensorischer
Nervenfasern und nachfolgender Freisetzung von Neuropeptiden, z. B. Substanz P und
Calcitonin Gene-related Peptide (CGRP) aus den peripheren Nervenendigungen. Die lokale
Entzündungsreaktion am Ort der Reizung besteht aus einer Hyperämie und einem Ödem,
die unter Umständen mit Schmerzen einhergehen. Die Entzündungszeichen und die Hyperalgesie
bei chronischen Schmerzsyndromen, z. B. der Migräne, Arthritiden und dem Komplexen
Regionalen Schmerzsyndrom entsprechen den Charakteristika der neurogenen Entzündung.
Aufgrund überzeugender Hinweise aus Tierversuchen, die überwiegend an Nagern durchgeführt
wurden, wird auch beim Menschen angenommen, dass die neurogene Entzündung an vielen
Erkrankungen der Atemwege, des Magendarmtraktes, des Urogenitaltraktes und der Haut
beteiligt sind. In Anbetracht der eher enttäuschenden Ergebnisse neuer klinischer
Studien zur Behandlung neurogener Entzündungen mit selektiven Substanz P- (NK1)-Antagonisten werden in dieser Übersicht die Hypothesen einer Beteiligung neurogener
Entzündungen an Erkrankungen beim Menschen kritisch hinterfragt. Außer dem inflammatorischen
Charakter hat die neurogene Entzündung in ganz anderer Weise physiologisch eine besondere
Bedeutung. Sie hat eine protektive und nozifensive, aber auch trophische Funktion
und trägt mit zur Gewebeintegrität und -homöostase bei.
Abstract
Neurogenic inflammation is elicited by activation of unmyelinated sensory neurons
through noxious stimuli and subsequent release of neuropeptides such as substance
P and calcitonin gene-related peptide (CGRP) from peripheral nerve endings. The
nerve-mediated inflammatory responses in the tissue consist of hyperaemia and oedema
which under some circumstances may be accompanied by pain. Neurogenic inflammation
has been implicated in the pathophysiology of various human diseases with uncertain
etiology. Signs of inflammation and hyperalgesia associated with chronic pain syndromes
such as migraine, arthritis and complex regional pain syndrome resemble the characteristics
of neurogenic inflammation. By extrapolation of convincing evidence obtained in rodent
models, neurogenic inflammation is assumed to contribute to diseases of the respiratory
system, gastrointestinal tract, urogenital tract, and skin in humans. Since, however,
highly selective substance P receptor antagonists, found to be effective against inflammation
in rodents, failed to inhibit inflammatory processes in clinical trials, the hypothesis
of an involvement of neurogenic inflammation in human diseases is discussed critically
in this review. Beyond its primarily inflammatory character neurogenic inflammation
can be regarded as a mechanism that activates protective responses, thus bringing
about a first line of defence to maintain the integrity of the tissue and to contribute
to tissue repair.
Schlüsselwörter
Neurogene Entzündung - Pathophysiologie - Migräne - Arthritis
Keywords
Neurogenic inflammation - Pathophysiology - Migraine - Human diseases
Literatur
- 1
Holzer P.
Local effector functions of capsaicin-sensitive sensory nerve endings: involvement
of tachykinins, calcitonin gene-related peptide and other neuropeptides.
Neuroscience.
1988;
24
739-768
- 2
Holzer P.
Peptidergic sensory neurons in the control of vascular functions: mechanisms and significance
in the cutaneous and splanchnic vascular beds.
Rev Physiol Biochem Pharmacol.
1992;
121
49-146
- 3
Holzer P.
Neurogenic vasodilatation and plasma leakage in the skin.
Gen Pharmac.
1998;
30
5-11
- 4 Herbert M K, Holzer P. Die neurogene Entzündung. I. Grundlegende Mechanismen, Physiologie
und Pharmakologie. Anaesth Intensivmed Notfallmed Schmerzther (eingereicht)
- 5
Donnerer J, Amann R.
The inhibition of neurogenic inflammation.
Gen Pharmacol.
1993;
24
519-529
- 6
Holzer P.
Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory
neurons.
Pharmacol Rev.
1991;
43
143-201
- 7
Szallasi A, Blumberg P M.
Vanilloid receptors: new insights enhance potential as a therapeutic target.
Pain.
1996;
68
195-208
- 8
Resnick D, Niwayama G.
Entheses and enthesopathy.
Radiology.
1983;
146
1-9
- 9
Ball J.
Enthesopathy of rheumatoid and ankylosing spondylitis.
Ann Rheum Dis.
1971;
30
213-223
- 10
Niepel G A, Sitaj S.
Enthesopathy.
Clin Rheum Dis.
1979;
5
857-872
- 11
Ljung B O, Forsgren S, Friden J.
Substance P and calcitonin gene-related peptide expression at the extensor carpi radialis
brevis muscle origin: Implications for the etiology of tennis elbow.
J Orthop Res.
1999;
17
554-559
- 12
Haker E, Theodorsson E, Lundeberg T.
An experimental model of tennis elbow in rats: A study of the contribution of the
nervous system.
Inflammation.
1998;
22
435-444
- 13
Herbert M K, Tafler R, Schmidt R F, Weis K H.
Cyclooxygenase inhibitors acetylsalicylic acid and indomethacin do not affect capsaicin-induced
neurogenic inflammation in human skin.
Agents Actions.
1993;
38
C25-C27
- 14
Tafler R, Herbert M K, Schmidt R F, Weis K H.
Small reduction of capsaicin-induced neurogenic inflammation in human forearm skin
by the glucocorticoid prednicarbate.
Agents Actions.
1993;
38
31-34
- 15 Herbert M K. Neurogene Entzündung an Haut und Gelenk. Klinische und tierexperimentelle
Studien. Habilitationsschrift, Julius-Maximilians-Universität Würzburg 1994
- 16
Ferrell W R, Russell N J.
Extravasation in the knee induced by antidromic stimulation of articular C fibre afferents
of the anaesthetized cat.
J Physiol Lond.
1986;
379
407-416
- 17
Malone D G, Irani A M, Schwartz L B, Barrett K E, Metcalfe D D.
Mast cell numbers and histamine levels in synovial fluids from patients with diverse
arthritides.
Arthritis Rheum.
1986;
29
956-963
- 18
Marshall K W, Chiu B, Inman R D.
Substance P and arthritis: analysis of plasma and synovial fluid levels.
Arthritis Rheum.
1990;
33
87-90
- 19
Appelgren A, Appelgren B, Eriksson S, Kopp S, Lundeberg T, Nylander M, Theodorsson E.
Neuropeptides in temporomandibular joints with rheumatoid arthritis: a clinical study.
Scand J Dent Res.
1991;
99
519-521
- 20
Marabini S, Matucci C erinic, Geppetti P, Del Bianco E, Marchesoni A, Tosi S, Cagnoni M,
Partsch G.
Substance P and somatostatin levels in rheumatoid arthritis, osteoarthritis, and psoriatic
arthritis synovial fluid.
Ann N Y Acad Sci.
1991;
632
435-436
- 21
Joyce T J, Yood R A, Carraway R E.
Quantitation of substance-P and its metabolites in plasma and synovial fluid from
patients with arthritis.
J Clin Endocrinol Metab.
1993;
77
632-637
- 22
Anichini M, Cesaretti S, Lepori M, Maddali-Bongi S, Maresca M, Zoppi M.
Substance P in the serum of patients with rheumatoid arthritis.
Rev Rhum Engl Ed.
1997;
64
18-21
- 23
Arnalich F, de Miguel E, Perez Ayala C, Martinez M, Vazquez J J, Gijon B anos, Hernanz A.
Neuropeptides and interleukin-6 in human joint inflammation relationship between intraarticular
substance P and interleukin-6 concentrations.
Neurosci Lett.
1994;
170
251-254
- 24
Courtright L J, Kuzell K C.
Sparing effect of neurological deficit and trauma on the course of adjuvant arthritis
in the rat.
Ann Rheum Dis.
1965;
24
360-368
- 25
Colpaert F C, Donnerer J, Lembeck F.
Effects of capsaicin on inflammation and on the substance P content of nervous tissues
in rats with adjuvant arthritis.
Life Sci.
1983;
32
1827-1834
- 26
Levine J D, Dardick S J, Roizen M F, Helms C, Basbaum A I.
Contribution of sensory afferents and sympathetic efferents to joint injury in experimental
arthritis.
J Neurosci.
1986;
6
3423-3429
- 27
Levine J D, Clark R, Devor M, Helms C, Moskowitz M A, Basbaum A I.
Intraneuronal substance P contributes to the severity of experimental arthritis.
Science.
1984;
226
547-549
- 28
Levine J D, Moskowitz M A, Basbaum A I.
The contribution of neurogenic inflammation in experimental arthritis.
J Immunol.
1985;
135
843s-847s
- 29
Basbaum A I, Levine J D.
The contribution of the nervous system to inflammation and inflammatory disease.
Can J Physiol Pharmacol.
1991;
69
647-651
- 30
Donnerer J, Amann R, Lembeck F.
Neurogenic and non-neurogenic inflammation in the rat paw following chemical sympathectomy.
Neuroscience.
1991;
45
761-765
- 31
Koltzenburg M, Kress M, Reeh P W.
The nociceptor sensitization by bradykinin does not depend on sympathetic neurons.
Neuroscience.
1992;
46
465-473
- 32
Cambridge H, Brain S D.
The role of sympathetic nerves in bradykinin (BK) induced plasma extravasation in
the rat knee joint.
Can J Physiol Pharmacol.
1994;
72
(Suppl 2)
38-40
- 33
Donnerer J, Schuligoi R, Stein C.
Increased content and transport of substance P and calcitonin gene-related peptide
in sensory nerves innervating inflamed tissue: evidence for a regulatory function
of nerve growth factor in vivo.
Neuroscience.
1992;
49
693-698
- 34
Kuraishi Y, Nanayama T, Ohno H, Fujii N, Otaka A, Yajima H, Satoh M.
Calcitonin gene-related peptide increases in the dorsal root ganglia of adjuvant arthritic
rat.
Peptides.
1989;
10
447-452
- 35
Marlier L, Poulat P, Rajaofetra N, Privat A.
Modifications of serotonin-, substance P- and calcitonin gene-related peptide-like
immunoreactivities in the dorsal horn of the spinal cord of arthritic rats: a quantitative
immunocytochemical study.
Exp Brain Res.
1991;
85
482-490
- 36
Maleki J, LeBel A A, Bennett G J, Schwartzman R J.
Patterns of spread of complex regional pain syndrome, type I (reflex sympathetic dystrophy).
Pain.
2000;
88
259-266
- 37
Pedersen-Bjergaard U, Nielsen L B, Jensen K, Edvinsson L, Jansen I, Olesen J.
Calcitonin gene-related peptide, neurokinin A and substance P: effects on nociception
and neurogenic inflammation in human skin and temporal muscle.
Peptides.
1991;
12
333-337
- 38
Wallengren J, Hakanson R.
Effects of substance P, neurokinin A and calcitonin gene-related peptide in human
skin and their involvement in sensory nerve-mediated responses.
Eur J Pharmacol.
1987;
143
267-273
- 39
Stewart J M, Getto C J, Neldner K, Reeve E B, Kirvoy W A, Zimmermann E.
Substance P and analgesia.
Naunyn Schmiedeberg's Arch. Pharmacol..
1976;
262
784-785
- 40
Kessler W, Kirchhoff C, Reeh P W, Handwerker H O.
Excitation of cutaneous afferent nerve endings in vitro by a combination of inflammatory
mediators and conditioning effect of substance P.
Exp Brain Res.
1992;
91
467-476
- 41
Herbert M K, Schmidt R F.
Sensitization of articular afferents to mechanical stimuli by substance P.
Inflamm Res.
2001;
50
275-282
- 42
Culp W J, Ochoa J, Cline M, Dotson R.
Heat and mechanical hyperalgesia induced by capsaicin. Cross modality threshold modulation
in human C nociceptors.
Brain.
1989;
112
1317-1331
- 43
Cervero F, Gilbert R, Hammond R G, Tanner J.
Development of secondary hyperalgesia following non-painful thermal stimulation of
the skin: a psychophysical study in man.
Pain.
1993;
54
181-189
- 44
Kilo S, Schmelz M, Koltzenburg M, Handwerker H O.
Different patterns of hyperalgesia induced by experimental inflammation in human skin.
Brain.
1994;
117
385-396
- 45
Coderre T J, Melzack R.
Cutaneous hyperalgesia: contributions of the peripheral and central nervous systems
to the increase in pain sensitivity after injury.
Brain Res.
1987;
404
95-106
- 46
Baumann T K, Simone D A, Shain C N, LaMotte R H.
Neurogenic hyperalgesia: the search for the primary cutaneous afferent fibers that
contribute to capsaicin-induced pain and hyperalgesia.
J Neurophysiol.
1991;
66
212-227
- 47
LaMotte R H, Shain C N, Simone D A, Tsai E F.
Neurogenic hyperalgesia: psychophysical studies of underlying mechanisms.
J Neurophysiol.
1991;
66
190-211
- 48
LaMotte R H, Lundberg L E, Torebjörk H E.
Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal
injection of capsaicin.
J Physiol Lond.
1992;
448
749-764
- 49
Simone D A, Sorkin L S, Oh U, Chung J M, Owens C, LaMotte R H, Willis W D.
Neurogenic hyperalgesia: central neural correlates in responses of spinothalamic tract
neurons.
J Neurophysiol.
1991;
66
228-246
- 50
Torebjörk H E, Lundberg L E, LaMotte R H.
Central changes in processing of mechanoreceptive input in capsaicin-induced secondary
hyperalgesia in humans.
J Physiol Lond.
1992;
448
765-780
- 51
Reeh P W, Kocher L, Jung S.
Does neurogenic inflammation alter the sensitivity of unmyelinated nociceptors in
the rat?.
Brain Res.
1986;
384
42-50
- 52
Meyer R A, Campbell J N, Raja S N.
Antidromic nerve stimulation in monkey does not sensitize unmyelinated nociceptors
to heat.
Brain Res.
1988;
441
168-172
- 53
Ray B S, Wolff H G.
Experimentel studies on headache. Pain-sensitive structures of the head and their
significance in headache.
Arch Surg.
1940;
41
813-856
- 54 Moskowitz M A, Lee W S, Cutrer F M.
Sensory neuropeptides in migraine. Geppetti P, Holzer P (eds) Neurogenic inflammation. CRC Press, Boca Raton New York
London Tokyo 1996: 187-199
- 55
Buzzi M G, Bonamini M, Moskowitz M A.
Neurogenic model of migraine.
Cephalalgia.
1995;
15
277-280
- 56
May A, Shepheard S L, Knorr M, Effert R, Wessing A, Hargreaves R J, Goadsby P J, Hiener H C.
Retinal plasma extravasation in animals but not in humans: implications for the pathophysiology
of migraine.
Brain.
1998;
121
1231-1237
- 57
May A, Goadsby P J.
Substance P receptor antagonists in the therapy of migraine.
Expert Opin Investig Drugs.
2001;
10
673-678
- 58
Escott K J, Beattie D T, Connor H E, Brain S D.
Trigeminal ganglion stimulation increases facial skin blood flow in the rat: a major
role for the calcitonin gene-related peptide.
Brain Res.
1995;
669
93-99
- 59
Messlinger K, Hanesch U, Kurosawa M, Pawlak M, Schmidt R F.
Calcitonin gene related peptide released from dural nerve fibers mediates increase
of meningeal blood flow in the rat.
Can J Physiol Pharmacol.
1995;
73
1020-1024
- 60
Feuerstein G, Wilette R, Aiyar N.
Clinical perspectives of calcitonin gene related peptide pharmacology.
Can J Physiol Pharmacol.
1995;
73
1070-1074
- 61
O'Connor T P, van der Kooy D.
Pattern of intracranial and extracranial projections of trigeminal ganglion cells.
J Neurosci.
1986;
6
2200-2207
- 62
Phebus L A, Johnson K W, Stengel P W, Lobb K L, Nixon J A, Hipskind P A.
The non-peptide receptor antagonist LY 303870 inhibits neurogenic dural infalmmation
in guinea pigs.
Life Sci.
1997;
60
1553-1561
- 63
Shepheard S L, Williamson D J, Hill R G, Hargreaves R J.
The non-peptide neurokinin-1 receptor antagonist, RP 67580, blocks neurogenic plasma
extravasation in the dura mater of rats.
Br J Pharmacol.
1993;
108
11-12
- 64
Lee W S, Moussaoui S M, Moskowitz M A.
Oral or parenteral non-peptide NK1 receptor antagonist RpR 100,893 blocks neurogenic plasma extravasation within guinea-pig
dura mater and conjunctiva.
Br J Pharmacol.
1994;
112
920-924
- 65
Buzzi M G, Carter W B, Shimizu T, Heath H, Moskowitz M A.
Dihydroergotamine and sumatriptan attenuate levels of CGRP in plasma in rat superior
sagittal sinus during electrical stimulation of the trigeminal anglion.
Neuropharmacology.
1991;
30
1193-1200
- 66
Goadsby P J, Edvinsson L, Ekam R.
Release of vasoactive peptides in the extracerebral circulation in humans and the
cat during activation of the trigeminovascular system.
Ann Neurol.
1993;
23
193-196
- 67
Buzzi M G, Moskowitz M A.
The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma
extravasation from blood vessels in dura mater.
Br J Pharmacol.
1990;
99
202-206
- 68
Lee W S, Moskowitz M A.
Conformationally restricted sumatriptan analogues, CP-122,288 and CP-122,638 exhibit
enhanced potency against neurogenic inflammation in dura mater.
Brain Res.
1993;
626
303-305
- 69
Gupta P, Brown D, Butler P, Ellis P, Grayson K L, Land G C, Macor J E, Robson S F,
Wythes M J, Shepperson N B.
The in vivo pharmacological profile of a 5-HT1 receptor agonist, CP-122,288, a selective
inhibitor of neurogenic inflammation.
Br J Pharmacol.
1995;
116
2385-2390
- 70
Cutrer F M, Moskowitz M A.
Wolff Award 1996. The actions of valproate and neurosteroids in a model of trigeminal
pain.
Headache.
1996;
36
579-585
- 71
Brändli P, Löffler B M, Breu V, Osterwalder R, Maire J P, Clozel M.
Role of endothelin in mediating neurogenic plasma extravasation in rat dura mater.
Pain.
1995;
64
315-322
- 72
Ebersberger A, Schaible H G, Averbeck B, Richter F.
Is there a correlation between spreading depression, neurogenic inflammation, and
nociception that might cause migraine headache?.
Ann Neurol.
2001;
49
7-13
- 73
Lauritzen M.
Pathophysiology of the migraine aura: the spreading depression theory.
Brain.
1994;
117
199-210
- 74
Olesen J, Larsen B, Lauritzen M.
Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in
classic migraine.
Ann Neurol.
1981;
9
344-352
- 75
Leao A AP.
Spreading depression of activity in the cerebral cortex.
J Neurophysiol.
1944;
7
359-390
- 76
Gardner-Medwin A R.
Possible roles of vertebrate neuroglia in potassium dynamics, spreading depression
and migraine.
J Exp Biol.
1981;
95
111-127
- 77
Moskowitz M A, Macfarlane R.
Neurovascular and molecular mechanisms in migraine headaches.
Cerebrovasc Brain Metab Rev.
1993;
5
159-177
- 78
Roon K I, Olesen J, Diener H C, Ellis P, Hettiarachchi J, Poole P H, Christianssen I,
Kleinermans D, Kok J G, Ferrari M D.
No acute antimigraine effect of CP-122,288, a highly potent inhibitor of neurogenic
inflammation: Results of two randomized, double-blind, placebo controlled clinical
trials.
Ann Neurol.
2000;
47
238-241
- 79
Herbert M K, Holzer P.
Warum versagen Substanz P (NK1)-Rezeptoren in der Schmerztherapie?.
Anaesthesist.
2002;
51
308-319
- 80
Szolcsanyi J, Bartho L.
Capsaicin-sensitive non-cholinergic excitatory innervation of the guinea-pig tracheobronchial
smooth muscle.
Neurosci Lett.
1982;
34
247-251
- 81
Szolcsanyi J.
Tetrodotoxin-resistant noncholinergic neurogenic contraction evoked by capsaicinoids
and piperine on the guinea-pig trachea.
Neurosci Lett.
1983;
42
83-88
- 82
Lundberg J M, Saria A.
Bronchial smooth muscle contraction induced by stimulation of capsaicin-sensitive
sensory neurons.
Acta Physiol Scand.
1982;
116
473-476
- 83
Lundberg J M, Saria A.
Capsaicin-induced desensitization of airway mucosa to cigarette smoke, mechanical
and chemical irritants.
Nature.
1983;
302
251-253
- 84
Yamawaki I, Tamaoki J, Takeda Y, Nagai A.
Inhaled cromoglycate reduces airway neurogenic inflammation via tachykinin antagonism.
Res Commun Mol Pathol Pharmacol.
1997;
98
265-272
- 85
Aizawa H, Koto H, Nakano H, Inoue H, Matsumoto K, Takata S, Shigyo M, Hara N.
The effect of a specific tachykinin receptor antagonist FK-224 on ozone-induced airway
hyperresponsiveness and inflammation.
Respirology.
1997;
2
261-265
- 86
Delay-Goyet P, Satoh H, Lundberg J M.
Relative involvement of substance P and CGRP mechanisms in antidromic vasodilation
in the rat skin.
Acta Physiol Scand.
1992;
146
537-538
- 87
Quartara L, Maggi C A.
The tachykinin NK1 receptor. Part II: distribution and pathophysiological roles.
Neuropeptides.
1998;
32
1-49
- 88
Scheerens H, Buckley T L, Muis T, van Loveren H, Nijkamp F P.
The involvement of sensory neuropeptides in toluene diisocyanate-induced tracheal
hypereactivity in the mouse airways.
Br J Pharmacol.
1996;
119
1655-1671
- 89
Lundberg J M.
Tachykinins, sensory nerves, and asthma - an overview.
Can J Physiol Pharmacol.
1995;
73
980-994
- 90
Barnes P J.
Overview of neural mechanisms in asthma.
Pulm Pharmacol.
1995;
8
151-159
- 91
Barnes P J.
Neuroeffector mechanisms: The interface between inflammation and neuronal responses.
J Allergy Clin Immunol.
1996;
98
S73-S83
- 92
Barnes P J.
Neurogenic inflammation in the airways.
Respir Physiol.
2001;
125
145-154
- 93
Rumsey W L, Aharanoy D, Bialecki R A, Abbott B M, Barthlow H G, Caccese R, Ghanekar S,
Lengel D, McCarthy M, Wenrich B, Undem B, Ohnmacht C, Shenvi A, Albert J S, Brown F,
Bernstein P R, Russell K.
Pharmacological characterization of ZD6021: A novel, orally active antagonist of the
tachykinin receptors.
J Pharmacol Exp Ther.
2001;
298
307-315
- 94
Tampo T, Nabe T, Yasui K, Kamiki T, Kohno S.
Participation of neuropeptides in antigen-induced contraction of guinea pig bronchi
via NK2 but not NK1 receptor stimulation.
Pharmacology.
2000;
60
169-174
- 95
Lundblad L, Anggard A, Lundberg J M.
Effects of antidromic trigeminal nerve stimulation in relation to parasympathetic
vasodilatation in the cat nasal mucosa.
Acta Physiol Scand.
1983;
119
7-13
- 96
Asakura K, Shirasaki H, Narita S, Kojima T, Kautura A.
Study on the dye leakage response of nasal mucosa following topical capsaicin challenge
in guinea-pigs.
Acta Otolaryngol.
1992;
112
545-551
- 97
Petterson G, Malm L, Ekman R, Hakanson R.
Capsaicin evokes secretion of nasal fliud and depletes substance P and CGRP from the
nasal mucosa in the rat.
Br J Pharmacol.
1989;
98
930-936
- 98
Evangelista S, Paoli S, Giachetti A, Manzini S.
Involvement of tachykinin NK1 receptors in plasma protein extravasation induced by tachykinins in the guinea-pig
upper airways.
Neuropeptides.
1997;
31
65-70
- 99
Geppetti P, Fusco B M, Marabini S, Maggi C A, Fanciullacci M, Sicuteri F.
Secretion, pain and sneezing induced by application of capsaicin to the nasal mucosa
in man.
Br J Pharmacol.
1988;
93
503-514
- 100
Philip G, Baroody F M, Proud D, Naclerio R M, Togias A G.
The human nasal response to capsaicin.
J Allergy Clin Immunol.
1994;
94
1035-1045
- 101
Greiff L, Svensson C, Andersson M, Persson C G.
Effects of topical capsaicin in seasonal allergic rhinitis.
Thorax.
1995;
50
225-229
- 102
Sanico A M, Satsuki A, Proud D, Togias A.
Dose-dependent effects of capsaicin nasal challenge: In vivo evidence of human airway
neurogenic inflammation.
J Allergy Clin Immunol.
1997;
100
632-641
- 103
Baraniuk J N, Lundgren J D, Okayama M, Merida M, Kaliner M A.
Substance P and neurokinin A in human nasal mucosa.
Am J Resp Cell Mol Biol.
1991;
4
228-236
- 104
Joos G F, Kips J C, Peleman R A, Pauwels R A.
Tachykinin antagonists and the airways.
Arch Int Pharmacodyn.
1995;
329
205-219
- 105
Rogers D F.
Reflexly running noses: neurogenic inflammation in the nasal mucosa.
Clin Exp Allergy.
1996;
26
365-367
- 106
Baraniuk J N, Kaliner M.
Neuropeptides and nasal secretion.
Am J Physiol.
1991;
261
L223-L235
- 107
Mantyh C R, Gates T S, Zimmerman R P, Welton M L, Passaro E P, Vigna S R, Magio J E,
Kruger L, Mantyh P W.
Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed
in high concentrations by arterioles, venules, and lymph nodules in surgical specimens
obtained from patients with ulcerative colitis and Crohn disease.
Proc Natl Acad Sci USA.
1988;
85
3235-3239
- 108
Swain M G, Agro A, Blennerhassett P, Stanisz A, Collins S M.
Increased levels of substance P in the myenteric plexus of trichinella-infected rats.
Gastroenterology.
1992;
102
1913-1919
- 109
Pothoulakis C, Castagliuolo I, LaMont J T, O'Keane J C, Snider R M, Leeman S E.
CP-96,345, a substance P antagonist, inhibits rat intestinal responses to Clostridium
difficile A but not cholera toxin.
Proc Natl Acad Sci USA.
1995;
91
947-951
- 110
McVey D C, Vigna S R.
The capsaicin VR1 receptor mediates substance P release in toxin A-induced enteritis
in rats.
Peptides.
2001;
22
1439-1446
- 111
Croci T, Landi M, Edmonds X, Le Furg G, Maffrand J P, Manara L.
Role of tachykinins in castor oil induced diarrhea in rats.
Br J Pharmacol.
1997;
121
375-380
- 112
Stucchi A F, Shofer S, Leeman S, Materne O, Beer E, McClung A, Shebani K, Moore F,
O'Brien M, Becker J M.
NK-1 antagonist reduces colonic inflammation and oxidative stress in dextran sulfate-induced
colitis in rats.
Am J Physiol Gastrointest Liver Physiol.
2000;
279
G1298-G1306
- 113
Sann H, Dux M, Schemann M, Jancso G.
Neurogenic inflammation in the gastrointestinal tract of the rat.
Neurosci Lett.
1996;
219
147-130
- 114
Yiangou Y, Facer P, Dyer N HC, Chan C LH, Knowles C, Williams N S, Anand P.
Vanilloid receptor 1 immunoreactivity in inflamed human bowel.
Lancet.
2001;
357
1338-1339
- 115
Sturiale S, Barbara G, Qiu B, Figini M, Geppetti P, Gerard N, Gerard C, Grady E F,
Bunnett N W, Collins S M.
Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P.
Proc Natl Acad Sci USA.
1999;
96
11653-11658
- 116
Talmage E K, Pouliot W A, Cornbrooks E B, Mawe G M.
Transmitter diversity in ganglion cells of the guinea pig gallbladder: An immunohistochemical
study.
J Comp Neurol.
1992 ;
317
45-56
- 117
Mawe G, Gershon M D.
Structure, afferent innervation, and transmitter content of ganglia of the guinea
pig gallbladder: Relationship to the enteric nervous system.
J Comp Neurol.
1989 ;
283
374-390
- 118
de Giorgio R, Zittel T T, Parodi J E, Becker J M, Brunicardi F C, Go V LW, Brecha N C,
Sternini C.
Peptide immunoreactivities in the ganglionated olexuses and nerve fibres innervating
the human gallbladder.
J Auton Nerv Syst.
1995;
51
37-47
- 119
Jivegard L, Thornell E, Svanvik J.
Fluid secretion by gallblader mucosa in experimental cholecystitis is influenced by
intramural nerves.
Dig Dis Sci.
1987;
32
389-1394
- 120
Prystowsky J B, Rege R V.
Neurogenic inflammation in cholecystitis.
Dig Dis Sci.
1997;
42
1489-1494
- 121 Maggi C A.
The dual, sensory and „efferent” function of the capsaicin-sensitive primary sensory
neurons in the urinary bladder and urethra. Maggi CA (ed) Nervous control of the urogenital system. Hardwood Publisher 1993:
383-422
- 122
Lecci A, Maggi C A.
Tachykinins as modulators of the micturition reflex in the central and peripheral
nervous system.
Regul Peptides.
2001;
101
1-18
- 123
Maggi C A, Patacchini R, Rovero P, Giachetti A.
Tachykinin receptors and tachykinin receptor antagonists.
J Auton Pharmacol.
1993;
13
23-93
- 124
Ahluwalia A, Giuliani S, Scotland R, Maggi C A.
Ovalbumin-induced neurogenic inflammation in the bladder of sensitized rats.
Br J Pharmacol.
1998;
124
190-196
- 125
de Ridder D, Chandiramani V, Dasgupta P, van Poppel H, Baert L, Fowler C J.
Intravesical capsaicin as a treatment for refractory detrusor hyperreflexia: A dual
center study with long-term followup.
J Urol.
1997;
158
2087-2092
- 126
Cruz F, Guimaraes M, Silva C, Rio M E, Coimbra A, Reis M.
Desensitization of bladder sensory fibers by intravesical capsaicin has long lasting
clinical and urodynamic effects on patients with hyperactive or hypersensitive bladder
dysfunction.
J Urol.
1997;
157
585-589
- 127
Elbadawi A.
Interstitial cystitis: a critique of current concepts with a new proposal for pathologic
diagnosis and pathogenesis.
Urology.
1997;
49
(Suppl 5A)
14-40
- 128
Theoharides T C, Kempuraj D, Sant G R.
Mast cell involvement in interstitial cystitis: a review of human and experimental
evidence.
Urology.
2001;
57
(Suppl)
47-55
- 129
Wesselmann U.
Neurogenic inflammation and chronic pelvic pain.
World J Urol.
2001;
19
180-185
- 130
Scholzen T, Armstrong C A, Bunnett N W, Luger T A, Olerud J E, Ansel J C.
Neuropeptides in the skin: interactions between the neuroendocrine and skin immune
systems.
Exp Dermatol.
1998;
7
81-96
- 131
Johansson O, Virtanen M, Hilliges M.
Histaminergic nerves demonstrated in the skin. A new direct mode of neurogenic inflammation?.
Exp Dermatol.
1995;
4
93-96
- 132
Brzezinska-Blaszczyk E, Zalewska A.
In vitro reactivity of mast cells in urticaria pigmentosa skin.
Arch Dermatol Res.
1998;
290
14-17
- 133 Brain S M.
Sensory neuropeptides in the skin. Geppetti P, Holzer P (eds) Neurogenic inflammation. CRC Press, Boca Raton New York
London Tokyo 1996: 229-244
- 134
Liang Y, Jacobi H H, Reimert C M, Haak-Frendscho M, Marcusson J A, Johansson O.
CGRP-immunoreactive nerves in prurigo nodularis - an exploration of neurogenic inflammation.
J Cutan Pathol.
2000;
27
359-366
- 135
Rossi R, Johannson O.
Cutaneous innervation and the role of neuronal peptides in cutaneous inflammation:
a minireview.
Eur J Dermatol.
1998;
8
299-306
- 136
Maggi C A.
Tachykinins and CGRP as co-transmitters released from peripheral endings of sensory
nerves.
Prog Neurobiology.
1995;
45
1-98
- 137
Kjartansson J, Dalsgaard C J, Jonsson C E.
Decreased survival of experimental critical flaps in rats after sensory denervation
with capsaicin.
Plast Reconstr Surg.
1987;
79
218-221
- 138
Khalil Z, Helme R.
Sensory peptides as neuromodulators of wound healing in aged rats.
J Gerontology.
1996;
51A
B354-B361
- 139
Gherardini G, Gürlek A, Milner S M, Matarasso A, Evans G RD, Jernbeck J, Lundeberg .
Calcitonin gene-related peptide improves skin flap survival and tissue inflammation.
Neuropeptides.
1998;
32
269-273
- 140
Németh J, Szilvássy Z, Thán M, Oroszi G, Sári R, Szolcsányi J.
Decreased sensory neuropeptide release from trachea of rats with streptozotocin-induced
diabetes.
Eur J Pharmacol.
1999;
369
221-224
- 141
Walmsley D, Wiles P G.
Early loss of neurogenic inflammation in the human diabetic foot.
Clin Sci Colch.
1991;
80
605-610
- 142
Gyorfi A, Feazekas A, Feher E, Ender F, Rosivall L.
Effects of streptocotozin-induced diabetes on neurogenic inflammation of gingivomusocal
tissue in rat.
J Periodontal Res.
1996;
31
249-255
- 143
Forst T, Pfutzner A, Kunt T, Pohlmann T, Schenk U, Bauersachs R, Kustner E, Beyer J.
Clin Sci.
Clin Sci.
1998;
94
255-261
- 144
Gamse R, Jancso G.
Reduced neurogenic inflammation in streptozotocin-diabetic rats due to microvascular
changes but not to substance P depletion.
Eur J Pharmacol.
1985;
118
175-180
- 145
Diemel L T, Stevens E J, Willars G B, Tomlinson D R.
Depletion of substance P and calcitonin gene-related peptide in sciatic nerve of rats
with experimental diabetes; effects of insulin and aldose reductase inhibition.
Neurosci Lett.
1992;
137
253-256
- 146
Németh J, Thán M, Sári R, Peitl B, Oroszi G, Farkas B, Szolcsányi J, Szilvássy Z.
Impairment of neurogenic inflammation and anti-inflammatory responses in diabetic
rats.
Eur J Pharmacol.
1999;
386
83-88
- 147 Ziche M.
Sensory neuropeptides: mitogenic and trophic functions. Geppetti P, Holzer P (eds) Neurogenic inflammation. CRC Press, Boca Raton New York
London Tokyo 1996: 253-263
- 148
Fan T P, Hu D E, Guard S, Gresham G A, Watling K J.
Stimulation of angiogenesis by substance P and interleukin-1 in the rat and its inhibition
by interleukin-1 or interleukin-1 receptor antagonists.
Br J Pharmacol.
1993;
110
43-49
- 149
Ziche M, Morbidelli L, Masini E, Amerini S, Granger H J, Maggi C A, Geppetti P,
Ledda F.
Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration
in vitro promoted by subtance P.
J Clin Invest.
1994;
94
2036-2044
Priv.-Doz. Dr. med. Michael K. Herbert
Klinik für Anaesthesiologie der Universität Würzburg
Josef-Schneider-Straße 2
97080 Würzburg
Email: mherbert@anaesthesie.uni-wuerzburg.de
