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SCHMERZ Sir Charles Bell. The Anatomy and Philosophy of Expression: as Connected with the Fine Arts. 5th ed. London : Henry G. Bohn, 1865

SCHMERZ - phys.szote.u-szeged.hu · „Schmerz ist ein unangenehmes Sinnes- oder Gefühlserlebnis, das mit tatsächlicher neuropathiás fájdalom oder potentieller Gewebeschädigung

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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)

Inzidenz chronischer Schmerzen in Europa

Wirkung des Schmerzes auf die tägliche Aktivitäten

René Descartes. L'homme de Rene

Descartes. Paris: Angot, 1664

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”

Melzack R, Wall PD.

Pain mechanisms: a

new theory.

Science. 150:971-9

(1965)

Pat D. WALL

1925-2002

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

Sensibilisation Polymodaler Nozizeptoren

Aspirin:

Hemmung der

Prostaglandinsynthese

ÜBERTRÄGERSTOFFE DER

SCHMERZFASERN

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

Neurogenic

inflammation

H

H

H

Axon reflex flare (Vasodilatation)

(reflektorischer roter Hof)

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)

NOZICEPTOR

NGF

HHYPERALGESIA

PRIMARY SECONDARY

AT THE SITE OF INJURY OUTSIDE OF THE INJURY SITE

THERMAL AND MECHANICAL STIMULI MECHANICAL STIMULY ONLY

NOCICEPTOR SENSITIZATION CENTRAL SENSITIZATION

Periphere Sensibilisierung

Spezielle Schmerzformen

Übertragener Schmerz

Prostate

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:

Blinddarmentzündung

Projizierter Schmerz

BAHNEN DER

SCHMERZEMPFINDUNG

Brown-Séquard Syndrome

Spinothalamische Projektionsneurone im Rückenmark

Thalamic stimulation

Retrograde labelling

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

Die spinothalamische Bahn

Endogene Schmerzkontrolle

PAG-Stimulation induzierte Analgesie

Stress-Analgesie

Opiat/Morphin Analgesie

Aktivation des gyrus cinguli durch schmerzhafte Stimulation der Haut - fMRI

Schmerz-empathie

JUCKEN

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

Jacques-Louis David: Death of Marat

(1793, Musées Royaux des Beaux-Arts, Brussels)