Mechanismen neuropathischer Schmerzen am Beispiel der postherpetischen Neuralgie

J. Schattschneider; G. Wasner; A. Binder; R. Baron

doi:10.1055/s-0038-1626378

Nervenheilkunde, Table of Contents

Nervenheilkunde 2004; 23(05): 269-273
DOI: 10.1055/s-0038-1626378

Original- und Übersichtsarbeiten - Original and Review Articles

Schattauer GmbH

Mechanismen neuropathischer Schmerzen am Beispiel der postherpetischen Neuralgie

Übertragbarkeit tierexperimenteller Daten auf den MenschenMechanisms of neuropathic pain: Comparison of data from experimental models of neuropathic pain and patients with postherpetic neuralgia

Authors

J. Schattschneider

¹Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
G. Wasner

¹Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
A. Binder

¹Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
R. Baron

¹Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel

Abstract

Zusammenfassung

Die postherpetische Neuralgie ist eine häufige, mit schweren Schmerzen einhergehende Erkrankung. Anhand von Untersuchungen an Patienten und tierexperimentellen Daten zeigt sich, dass unterschiedliche pathophysiologische Mechanismen der Entstehung dieser Erkrankung zugrunde liegen. Bei einem Teil der Patienten besteht eine pathologische Spontanaktivität sensibilisierter C-Fasern (irritable nociceptors). Hierdurch entstehen sekundäre Veränderungen im Bereich des zentralen Nervensystems, die dazu führen, dass die Aktivierung mechanosensibler Aβ-Fasern als Schmerz wahrgenommen wird. Dies führt neben Spontanschmerzen und einer Hitzehyperalgesie zu einer ausgeprägten Allodynie. Bei einer anderen Gruppe von Patienten kann die Entzündung zu einer selektiven Degeneration schmerz- und temperaturleitender Nervenfasern führen. Diese ist gefolgt von einer anatomische Reorganisation auf Rückenmarksebene, die wiederum in einer Aktivierung primär schmerzleitender Neurone durch mechanosensible Aβ-Fasern resultiert. Klinisch besteht eine ausgeprägte Allodynie sowie eine durch die Degeneration der C-Fasern hervorgerufene thermische Hypästhesie. Schließlich kann durch die Affektion peripherer Nervenfasern eine Sensibilisierung nozizeptiver Fasern auf noradrenerge Substanzen erfolgen, die ebenfalls zur Unterhaltung der Schmerzen mit beitragen könnte.

Summary

Postherpetic neuralgia (PHN) is a common and often severely painful peripheral neuropathy. Our knowledge of the pain generating mechanisms in PHN has been increased by the comparison of PHN with experimental models of neuropathic pain. These studies suggest several pathophysiological mechanisms. In a subgroup of patients pathological active nociceptors can induce secondary changes in central processing leading to spinal cord hyperexcitability, that causes input from mechanoreceptive Aβ-fibres to be perceived as pain. These patients have serve allodynia and heat hyperalgesia. In another group of patients inflammation is followed by a degeneration of temperature and pain sensitive C-fibres, which leads to an impaired temperature perception. Anatomical reorganization in the dorsal horn resulting from degeneration may lead to Aβ-fibre mediated allodynia. Further on damaged peripheral nerve fibers are developing sensitivity to adrenergic substances, which is possible to contribute in generation of pain in PHN patients.

Schlüsselwörter

Postherpetische Neuralgie - Allodynie - Hyperalgesie - Pathophysiologie

Keywords

Postherpetic neuralgia - allodynia - hyperalgesia - pathophysiology

Full Text

References

Literatur
1 Helgason S, Petursson G, Gudmundsson S, Sigurdsson JA. Prevalence of postherpetic neuralgia after a first episode of herpes zoster: prospective study with long term follow up. Bmj 2000; 321: 794-6.
2 Baron R, Haendler G, Schulte H. Afferent large fiber polyneuropathy predicts the development of postherpetic neuralgia. Pain 1997; 73: 231-8.
3 Wall PD, Gutnick M. Ongoing activity in peripheral nerves: the physiology and pharmacology of impulses originating from a neuroma. Exp Neurol 1974; 43: 580-93.
4 Michaelis M, Boczek-Funcke A, Häbler HJ, Janig W. Responses of lumbar vasoconstrictor neurons supplying different vascular beds to graded baroreceptor stimuli in the cat. J Auton Nerv Syst 1993; 42: 241-9.
5 Michaelis M, Vogel C, Blenk KH, Jänig W. Algesics excite axotomised afferent nerve fibres within the first hours following nerve transection in rats. Pain 1997; 72: 347-54.
6 Burchiel KJ. Spontaneous impulse generation in normal and denervated dorsal root ganglia: sensitivity to alpha-adrenergic stimulation and hypoxia. Exp Neurol 1984; 85: 257-72.
7 Novakovic SD, Tzoumaka E, McGivern JG, Haraguchi M, Sangameswaran L, Gogas KR. et al. Distribution of the tetrodotoxin-resistant sodium channel PN3 in rat sensory neurons in normal and neuropathic conditions. J Neurosci 1998; 18: 2174-87.
8 Cummins TR, Waxman SG. Downregulation of tetrodotoxin-resistant sodium currents and upregulation of a rapidly repriming tetrodotoxin-sensitive sodium current in small spinal sensory neurons after nerve injury. J Neurosci 1997; 17: 3503-14.
9 Matzner O, Devor M. Hyperexcitability at sites of nerve injury depends on voltage-sensitive Na+ channels. J Neurophysiol 1994; 72: 349-59.
10 Nystrom B, Hagbarth KE. Microelectrode recordings from transected nerves in amputees with phantom limb pain. Neurosci Lett 1981; 27: 211-6.
11 Cline MA, Ochoa J, Torebjörk HE. Chronic hyperalgesia and skin warming caused by sensitized C nociceptors. Brain 1989; 112: 621-47.
12 Rowbotham MC, Fields HL. The relationship of pain, allodynia and thermal sensation in post- herpetic neuralgia. Brain 1996; 119: 347-54.
13 Rowbotham MC, Yosipovitch G, Connolly MK, Finlay D, Forde G, Fields HL. Cutaneous innervation density in the allodynic form of postherpetic neuralgia. Neurobiol Dis 1996; 03: 205-14.
14 Fields HL, Rowbotham M, Baron R. Postherpetic neuralgia: irritable nociceptors and deafferentation. Neurobiol Dis 1998; 05 (04) 209-27.
15 Baron R, Saguer M. Postherpetic neuralgia. Are C-nociceptors involved in signalling and maintenance of tactile allodynia? Brain 1993; 116: 1477-96.
16 Chabal C, Russell LC, Burchiel KJ. The effect of intravenous lidocaine, tocainide, and mexiletine on spontaneously active fibers originating in rat sciatic neuromas. Pain 1989; 38: 333-8.
17 Lynn B. Capsaicin: actions on nociceptive Cfibres and therapeutic potential. Pain 1990; 41: 61-9.
18 Rains C, Bryson HM. Topical capsaicin. A review of its pharmacological properties and therapeutic potential in post-herpetic neuralgia, diabetic neuropathy and osteoarthritis. Drugs Aging 1995; 07: 317-28.
19 McMahon SB, Wall PD. Receptive fields of rat lamina 1 projection cells move to incorporate a nearby region of injury. Pain 1984; 19: 235-47.
20 Cervero F, Laird JM, Pozo MA. Selective changes of receptive field properties of spinal nociceptive neurones induced by noxious visceral stimulation in the cat. Pain 1992; 51: 335-42.
21 Levine JD, Fields HL, Basbaum AI. Peptides and the primary afferent nociceptor. J Neurosci 1993; 13: 2273-86.
22 Davies SN, Lodge D. Evidence for involvement of N-methylaspartate receptors in ‘wind-up’ of class 2 neurones in the dorsal horn of the rat. Brain Res 1987; 424: 402-6.
23 Torebjörk HE, Vallbo AB, Ochoa JL. Intraneural microstimulation in man. Its relation to specificity of tactile sensations. Brain 1987; 110: 1509-29.
24 Simone DA, Ngeow JY, Putterman GJ, LaMotte RH. Hyperalgesia to heat after intradermal injection of capsaicin. Brain Res 1987; 418: 201-3.
25 Campbell JN, Raja SN, Meyer RA, Mackinnon SE. Myelinated afferents signal the hyperalgesia associated with nerve injury. Pain 1988; 32: 89-94.
26 Price DD, Bennett GJ, Rafii A. Psychophysical observations on patients with neuropathic pain relieved by a sympathetic block. Pain 1989; 36: 273-88.
27 Ochoa JL, Yarnitsky D. Mechanical hyperalgesias in neuropathic pain patients: dynamic and static subtypes. Ann Neurol 1993; 33: 465-72.
28 Eide PK, Jorum E, Stubhaug A, Bremnes J, Breivik H. Relief of post-herpetic neuralgia with the N-methyl-D-aspartic acid receptor antagonist ketamine: a double-blind, cross-over comparison with morphine and placebo. Pain 1994; 58: 347-54.
29 Baron R, Baron Y, Disbrow E, Roberts TP. Activation of the somatosensory cortex during Abeta-fiber mediated hyperalgesia. A MSI study. Brain Res 2000; 871: 75-82.
30 Lombard MC, Larabi Y. Electrophysiological study of cervical dorsal horn cells in partially deafferented rats. In: Bonica JJ. (ed). Advances in Pain Research and Therapy. New York: Raven Press; 1983: 147-54.
31 Devor M, Wall PD, Catalan N. Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction. Pain 1992; 48: 261-8.
32 Head H, Campbell AW. The pathology of herpes zoster and its bearing on sensory location. Brain 1900; 23: 353-523.
33 Zacks SI, Langfitt RW, Elliott FA. Herpetic neuritis: a light and electron microscopic study. Neurology 1964; 14: 744-50.
34 Ruppenthal M. Changes of the central nervous system in herpes zoater. Acta Neuropathol 1980; 52: 59-68.
35 Oaklander AL, Romans K, Horasek S, Stocks A, Hauer P, Meyer RA. Unilateral postherpetic neuralgia is associated with bilateral sensory neuron damage. Ann Neurol 1998; 44: 789-95.
36 Lewis T. Blood Vessels of the Human Skin and Their Responses. London: Shaw; 1927
37 Chapman LF. Mechanisms of the flare reaction in human skin. J Invest Dermatol 1977; 69: 88-97.
38 Baron R, Saguer M. Mechanical allodynia in postherpetic neuralgia: evidence for central mechanisms depending on nociceptive C-fiber degeneration. Neurology 1995; 45: S63-5.
39 Wall PD, Merrill EG, Yaksh TL. Responses of single units in laminae 2 and 3 of cat spinal cord. Brain Res 1979; 160: 245-60.
40 Woolf CJ, Shortland P, Coggeshall RE. Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature 1992; 355: 75-8.
41 Castro-Lopes JM, Coimbra A, Grant G, Arvidsson J. Ultrastructural changes of the central scalloped (C1) primary afferent endings of synaptic glomeruli in the substantia gelatinosa Rolandi of the rat after peripheral neurotomy. J Neurocytol 1990; 19: 329-37.
42 Laird JM, Bennett GJ. An electrophysiological study of dorsal horn neurons in the spinal cord of rats with an experimental peripheral neuropathy. J Neurophysiol 1993; 69: 2072-85.
43 Hu SJ, Zhu J. Sympathetic facilitation of sustained discharges of polymodal nociceptors. Pain 1989; 38: 85-90.
44 Sato J, Perl ER. Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury. Science 1991; 251: 1608-10.
45 Jänig W, Levine JD, Michaelis M. Interactions of sympathetic and primary afferent neurons following nerve injury and tissue trauma. Prog Brain Res 1996; 113: 161-84.
46 Devor M, Jänig W. Activation of myelinated afferents ending in a neuroma by stimulation of the sympathetic supply in the rat. Neurosci Lett 1981; 24: 43-7.
47 Kim SH, Chung JM. Sympathectomy alleviates mechanical allodynia in an experimental animal model for neuropathy in the rat. Neurosci Lett 1991; 134: 131-4.
48 Chung K, Yoon YW, Chung JM. Sprouting sympathetic fibers form synaptic varicosities in the dorsal root ganglion of the rat with neuropathic injury. Brain Res 1997; 751: 275-80.
49 Choi B, Rowbotham MC. Effect of adrenergic receptor activation on post-herpetic neuralgia pain and sensory disturbances. Pain 1997; 69: 55-63.
50 Shyu BC, Olausson B, Huang KH, Widerstrom E, Andersson SA. Effects of sympathetic stimulation on C-fibre responses in rabbit. Acta Physiol Scand 1989; 137: 73-84.