SCHMERZ
Sir Charles Bell. The Anatomy and Philosophy of Expression:
as Connected with the Fine Arts. 5th ed. London : Henry G. Bohn, 1865
„Schmerz ist ein unangenehmes Sinnes- oder
Gefühlserlebnis, das mit tatsächlicher
oder potentieller Gewebeschädigung einhergeht
oder von betroffenen Personen so beschrieben wird,
als wäre eine solche Gewebeschädigung die Ursache.“
A FÁJDALOM TÍPUSAI
akut v. fiziológiás fájdalom neuropathiás fájdalom (fantom-fájdalom, causalgia) gyulladásos fájdalom (hyperalgesia, allodynia)
Definition Schmerz
Schmerz ist ein unangenehmes Sinnes- oder
Gefühlserlebnis, das mit aktueller oder potentieller
Gewebeschädigung verknüpft ist oder mit Begriffen
einer solchen Schädigung beschrieben wird.
(International Association for the Study of Pain 1986)
„Schmerz ist ein unangenehmes Sinnes- oder Gefühlserlebnis,
das mit tatsächlicher oder drohender Gewebeschädigung
einhergeht oder von betroffenen Personen so beschrieben wird,
als wäre eine solche Gewebeschädigung die Ursache.“
Charles Scott Sherrington
(Nobel-Preis: 1932)
„Sedare dolorem opus divinum est”
(Hippocrates)
Osler: „morphine is God’s own medicine”
Der Schmerz ist von vitaler Bedeutung
in der Aufrechterhaltung der Integrität des Körpers
DIE BIOLOGISCHE BEDEUTUNG DES SCHMERZES
„although few people die of pain,
many people die in pain
and even more live in pain "
Gaius Mucius Scaevola was a noble and probably mythical Roman
youth, famous for his bravery.
When the Etruscan king Lars Porsenna held Rome under siege, Gaius
Mucius famously sneaked into the Etruscan camp and attempted to
murder Porsenna. His plot failed because he misindentified Porsenna
and killed the wrong man. Mucius was captured. He famously declared
to Porsenna: "I am Gaius Mucius, a citizen of Rome. I came here as an
enemy to kill my enemy, and I am as ready to die as I am to kill. We
Romans act bravely and, when adversity strikes, we suffer bravely."
(Ab Urbe Condita, II.12)
Porsenna, fearful and angry, ordered Mucius to be cast into the flames.
Mucius stoically accepted this punishment, preempting Porsenna by
thrusting his hand into that same fire and giving no sign of pain. For his
courage, Porsenna freed Mucius.
Because of his maimed right hand, Mucius was forever after known as
Scaevola ("lefty" or "left-handed"). (Ab Urbe Condita, II.13)
See Livy, Ab Urbe Condita (II.12-13) for the full story of Scaevola..
Gordon Scott portrayed Mucius in the 1964 peplum Hero of Rome, a
film loosely based on this story.
Retrieved from "http://en.wikipedia.org/wiki/Mucius"
<>
Peter Paul RUBENS
Mucius Scaevola before Porsenna.
1620.
Szépművészeti Múzeum, Budapest
Mucius Scævola
by Louis Pierre Deseine,
1791, Louvre Museum
Museum der Bildenden Künste
„Sedare dolorem
opus divinum est"
(Hippocrates)
(460-377 v. Chr.)
(460-377 v. Chr.)
(Es ist ein göttliches Werk,
Schmerz zu lindern)
Whites More Often Given Opioid Drugs,
Study Finds By ERIC NAGOURNEY, (January 8, 2008)
Opioid medications, the powerful painkillers that experts say have
been underused by doctors because of their stigma, are increasingly
being given in emergency rooms — but white patients are more
likely to get them than minorities, a new study finds.
But the researchers, whose report appears in the Jan. 2 Journal of the
American Medical Association, wanted to see if the increase extended
to emergency rooms. They also wanted to know if there was still a
tendency among doctors to withhold opioid drugs from blacks and
nonwhite Hispanics.
The answer to both questions is yes, the study found.
FROM New York Times
KONGENITALE ANALGESIE (congenital analgesia, congenital indifference to pain)
CONGENITAL UNIVERSAL INSENSITIVITY TO PAIN
BAXTER and OLSZEWSKI Brain.1960; 83: 381-393
(Fall der Tochter eines kanadischen Arztes)
(V.P.)
Dg.: Kongenitale Analgesie)
Kein Axon-reflex flare
Keine Schmerzempfindung auf
scharfschmeckende Paprika
Cold pressor test negativ
Wenig marklose Faser in
peripheren Nerven
N . suralis Biopsie
DIE BIOLOGISCHE BEDEUTUNG DES SCHMERZENS
The index case for the present study was a ten-year-old child, well
known to the medical service after regularly performing ‘street
theatre’. He placed knives through his arms and walked on
burning coals, but experienced no pain. He died before being
seen on his fourteenth birthday, after jumping off a house roof.
All six affected individuals had never felt any pain, at any
time, in any part of their body. Even as babies they had shown no
evidence of pain appreciation. None knew what pain felt like,
although the older individuals realized what actions should elicit pain
(including acting as if in pain after football tackles). All had injuries
to their lips (some requiring later plastic surgery) and/or tongue
(with loss of the distal third in two cases), caused by biting themselves
in the first 4 yr of life. All had frequent bruises and cuts, and most had
suffered fractures or osteomyelitis, which were only diagnosed in
retrospect because of painless limping or lack of use of a limb. The
children were considered of normal intelligence by their parents and
teachers, and by the caring physicians.
Detailed neurological examinations revealed that each could
correctly perceive the sensations of touch, warm and cold
temperature, proprioception, tickle and pressure, but not painful
stimuli.
we mapped the condition as an autosomal-recessive trait to
chromosome 2q24.3. This region contains the gene SCN9A,
encoding the a-subunit of the voltage-gated sodium
channel, Nav1.7, which is strongly expressed in nociceptive
neurons.
Our data suggest that SCN9A is an essential and non-redundant
requirement for nociception in humans. These findings should
stimulate the search for novel analgesics that selectively target this
sodium channel subunit.
BRAIN 2018: 141; 365–376
A novel human pain insensitivity disorder
caused by a point mutation in ZFHX2
Abdella M. Habib,1,2,* Ayako Matsuyama,1,* Andrei L. Okorokov,1,* Sonia Santana-Varela,1,* Jose T. Bras,3,*
Anna Maria Aloisi,4,* Edward C. Emery,1,* Yury D. Bogdanov,1,Maryne Follenfant,1 Sam J. Gossage,1 Mathilde
Gras,1 Jack Humphrey,1 Anna Kolesnikov,1 Kim Le Cann,1 Shengnan Li,1 Michael S. Minett,1 Vanessa Pereira,1
Clara Ponsolles,1 Shafaq Sikandar,1 Jesus M. Torres,1,5 Kenji Yamaoka,1 Jing Zhao,1 Yuriko Komine,6,Tetsuo
Yamamori,6 Nikolas Maniatis,7 Konstantin I. Panov,8 Henry Houlden,3, Juan D. Ramirez,9 David L. H. Bennett,9
Letizia Marsili,10 Valeria Bachiocco,4 John N. Wood1 and James J. Cox1
Here we have analysed an otherwise normal family where six affected
individuals display a pain insensitive phenotype that is characterized by
hyposensitivity to noxious heat and painless bone fractures. This
autosomal dominant disorder is found in three generations and is not
associated with a peripheral neuropathy. A novel point mutation in ZFHX2,
encoding a putative transcription factor expressed in small diameter sensory
neurons, was identified by whole exome sequencing that segregates with the
pain insensitivity. The mutation is predicted to change an evolutionarily
highly conserved arginine residue 1913 to a lysine within a homeodomain.
(UK) Subjektive Bewertung des Schmerzens
* Kategorisation
* Visuelle Analogskala (VAS)
* Effektivität der Schmerzlinderung
Verbale (deskriptive) Rating-Skalen (VRS)
Deskriptoren Visuelle Analogskala (VAS)
Betroffene nach Altersgruppen mit: (UK)
Johannes Müller (1801-1858)
[Helmholtz, DuBois-Reymond,
Schwann, Virchow, Kölliker and Remak]
Gesetz der spezifischen Sinnesenergien
1826
SCHMERZTHEORIEN:
Spezifizitätstheorie
Intensitätstheorie
Pattern
”GATE CONTROL” THEORIE
„Labelled line”
Eigenschaften von Nozizeptoren
* Nozizeptoren sind freie Nervenendigungen
* Nozizeptoren reagieren auf gewebsschädigende oder
potentiell gewebsschädigende Reize
* Nozizeptoren sind sensibilisierbar durch Modulatoren,
Entzündungsmediatoren
* morphologisch sind 2 Typen unterscheidbar:
Aδ-Fasern – heller, stechender Schmerz
(z.B. Verletzung)
C-Fasern – dumfer oder brennender,
anhaltender Schmerz
Tourniquet
Ischemie
Kälte
Druck
Local
Anestheticum
FELÜLETES (BŐR) FÁJDALOM TÍPUSAI Zusammenhang zwischen Aδ- und C-Faser Aktivität
und der subjektiven
Schmerzempfindung
POLYMODALER NOZIZEPTOR
Stechen
Nessel
Druck Druck
Druck elektrische Reizung
glühendes
Streichholz
Stechen
Th. LEWIS – Die Dreifache Reaktion der Haut - TRIPLE RESPONSE
lokale Rötung
reflektorischer roter Hof (flare)
lokales Oedem
(Quaddelbildung)
Orthodrome Leitung der
Nervenimpulse
Antidrome Leitung der Nervenimpulse
Axon-Reflex
Nervenendigungen der Haut
Arteriole
Paravaskulare Nervenendigungen
1. Microelectrode coated with SP antiserum
2. Sites which bind SP released from tissue do
not bind 3H-SP = no darkening on film
„black” areas
3. Sites which do not bind tissue-derived SP
bind 3H-SP = darkening on film
„white” areas
88)
ÜBERTRAEGERSTOFFE DER
SENSORISCHEN GANGLIENZELLEN
EXZITATORISCHE
AMINOSAURE
GLUTAMAT
ASPARTAT
NEUROPEPTIDE
SUBSTANZ P
CGRP
SOMATOSTATIN
GALANIN
PACAP
VIP
GALANIN
PURIN
ATP
GAS
NO
CAPSAICIN REZEPTOR – VR1 – TRPV1 [TRP Kanäle]
(transient receptor potential vanilloid type 1)
Nichtselektiver Kationkanal (Na+, Ca++)
(43 oC), Capsaicin(oide) [Vanilloide], pH < 5,3 (Protonen)
HHYPERALGESIA
PRIMARY SECONDARY
AT THE SITE OF INJURY OUTSIDE OF THE INJURY SITE
THERMAL AND MECHANICAL STIMULI MECHANICAL STIMULY ONLY
NOCICEPTOR SENSITIZATION CENTRAL SENSITIZATION
C. McBurney:
Experience with early operative interference in cases of
disease of the vermiform appendix.
New York Medical Journal, 1889, 50: 676-684.
Reprinted in Medical Classics, 1938; 2: 506-531.
Page 678: “The seat of greatest pain, determined by the
pressure of one finger, has been very exactly between
an inch and a half and two inches from the anterior
spinous process of the ilium on a straight line drawn
from that process to the umbilicus”.
Defense musculaire -Abwehrspannung der Muskeln
Appendicitis: Blinddarmentzündung A modern pain, costing about
$200 more than the old- fashioned stomach-ache. Source:
Paleospinothalamic:
projects exclusively to intralaminar thalamic nuclei
large receptive fields (whole body or face)
mediates diffuse burning pain
subserves general pain responses:
arousal, affect, autonomic responses
Neospinothalamic:
Projects to specific thalamic nuclei
Ventrobasal complex
posterior thalamic nuclei
small receptive fields
subserves pain localization and discrimination
Cerebral localization of pain: (PET studies)
SI: localization of pain
cingulate cortex: mediates affective components
anterior insular cortex: asymbolia to pain
Endogene Schmerzkontrolle
PAG-Stimulation induzierte Analgesie
Stress-Analgesie
Opiat/Morphin Analgesie
ITCH
Samuel Hafenreffer (1587-1660): „Juckreiz ist eine unangenehme Sensation, die Kratzen provoziert.“ Wens juckt, der kratze sich. (Spruch)
Samuel Hafenreffer bezeichnete den Puls als süßeste Lebensmelodie
und setzte bestimmte Pulsarten mit den vier Stimmlagen, den vier
Hauptintervallen und den vier Elementen in Verbindung.
ITCH AND PAIN
SPEZIFISCHE JUCKPUNKTE IDENTIFIZIRT IN DER HAUT
Shelley WE, Arthur RP. The neurohistology and neurophysiology of the itch
sensation in man. Arch Dermatol 1957; 76:296–323.
Török L. Über das Wesen der Juckempfindung. Ztschr Psychol 1907; 46:23–35.
MIKRONEURONOGRAPHY: N. PERONEUS
(KUTANER AST)
HISTAMINE-SENSITIVE MECHANO-
INSENSITIVE C-FASER
LEITUNGSGESCHWINDIGKEIT: SEHR
LANGSAM: < 0,5 m/s
UNGEWÖNLICH GROSSE REZEPTIVE
FELDER: DIAMETER: 24-85 mm
SENSITIV AUF WARM UND CAPSAICIN
[Schmelz et al, J Neurosci 17:8003, 1997]
SPEZIFISCHE HISTAMINE-SENSITIVE
C-FASER AFFERENZEN IN DER
MENSCHLICHEN HAUT
JUCKREZEPTOREN?
sensation (VAS)
SINGLE FIBER ACTIVITY