durerea neuropatica ex. neurologic
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EXAMENUL NEUROLOGIC IN DUREREA NEUROPATICA
Prof. Dr. Ovidiu Bajenaru
U.M.F. " Carol Davila " Bucuresti
Catedra de Neurologie
Spitalul Universitar de Urgenta Bucuresti
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1. DUREREA NOCICEPTIVA activarea de catre stimuli nociceptivi a cailor nervoase ale durerii care NU sunt lezate
2. DUREREA NEUROPATICA activarea de catre LEZIUNI PROPRII ale cailor
nervoase ale durerii ( periferice si centrale )
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Durerea nociceptiva Durerea nociceptiva este raspunsul fiziologic normal fata de stimuli nociceptivi
Tortora G, Grabowski SR. Principles of Anatomy and Physiology. 10th ed.2003.
Trauma
Informatie ascendenta Modulare descendenta
Ganglionul radacinii dorsale ( DRG )Tract spinotalamic
Nociceptori periferici
Nerv periferic
Corn dorsal
Durere
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1. RECEPTORII: TERMINATII NERVOASE LIBERE * STIMULI: mecanici, termici, chimici
2. CAI AFERENTE PERIFERICE ( in structura nn. priferici ): - fibre nemielinizate tip C - fibre putin mielinizate tip A-delta ( Aδ ) - fibre mielinizate tip A-beta ( A-β )
* leziuni tisulare mediatori chimici ( K+, H+, Hys-NH2, kinine, acizi lipoidici, citokine, tahikinine: SP, NKA, NKK )
► activeaza direct fibrele de tip C ► activeaza si cresc excitabilitatea nociceptorilor polimodali si mecanoreceptorilor cu prag inalt
3. GGL. RADACINII DORSALE
4. RADACINA DORSALA NN. SPINALI ( RAD. SENZITIVA NN.CRANIENI )
5. CAILE SENSIBILITATII ALGEZICE ( SPINO-TALAMO-CORTICALE )
6. CAILE DESCENDENTE MODULATOARE ALE DURERII
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Tipuri de fibre implicate in durerea neuropatica
Fibre Aβ • Diametru mare, mielinizate, viteza de conducere mare
• Mecanoreceptori normal activati de stimuli mecanici (atingere)
non-nociceptivi
Fibre Aδ
• Diametru mare, mielinizate, viteza de conducere intermediara
• Normal activate de stimuli nociceptivi ( transmit “ durerea ascutita ”)
Fibre C • Diametru mic, nemielinizate, viteza de conducere lenta
• Normal activate de stimuli nociceptivi (responsabili de durerea secundara, avand caracter de arsura, de suferinta dureroasa prelungita << ache >> )
Dworkin Clin J Pain. 2002;18:343-349Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. 1999.;11-57
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Durerea neuropatica: mecanisme
• Mecanisme periferice
- Hiperexcitabilitate membranara
• descarcari ectopice
- Sensibilizare periferica
• Mecanisme centrale
- Hiperexcitabilitate
membranara• descarcari ectopice
- “ Wind up ”
- Sensibilizare centrala
- Hipersensibilitate de denervare
- Pierderea controlului inhibitor
Attal N et al. Acta Neurol Scand. 1999;173:12-24. Woolf CJ et al. Lancet. 1999;353:1959-1964. Roberts et al. In Casey KL (Ed). Pain and central nervous system disease. 1991
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DUREREA NEUROPATICA – Mecanisme periferice- impulsuri cu punct de plecare:
* nociceptori sensibilizati
* ectopice ( leziuni pe caile aferente ) ► leziuni axonale ► leziuni demielinizante ► leziuni ischemice ► fibre regenerate nemielinizate/ putin mielinizate, * nevrom
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SENSIBILIZAREA PERIFERICA A NOCICEPTORILOR
- STIMUL NOCICEPTIV cond. ortodromica
conducere antidromica ( reflex de axon )eliberare din terminatii periferice:* mediatori ai inflamatiei INFLAMATIE NEUROGENA
sensibilizeaza nociceptorii vecini
* neuropeptide excitatorii ( subst. P, CGRP )
* NGF chemotropism pt. neurite SINAPTOGENEZA ( fenomen de aparare a neuronilor lezati )
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Peripheral Sensitization
Innocuous stimulus
Primary afferent nerve fibers Dorsal horn neurons
Neuropeptide release
NGF
NGF
NGF
NGF
Pain sensation
Woolf and Mannion. Lancet 1999;353:1959-1964
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AXONI REGENERATI: * mai subtiri, mielina putina* distante internodale mai scurte
* depolarizare: stimuli chimici, mecanici ► remodelarea axolemei
insertia de canale ionice & transductori senzitivi ( NU sunt prezente in conditii normale )
► nevroame (fibre regenerate care nu se pot alungi ) - foarte sensibile la presiune - spontan active
AXONI COLATERALI REGENERATI ( axoni adiacenti nelezati )
AXONI REGENERATI & AXONI COLATERALI REGENERATI* comunicare electrica incrucisata ( “ cross-talk” ) intre fb.
stimulare aberanta a unei fibre de catre alta fibra
( TRANSMITERE EFAPTICA )
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Ectopic DischargesInjured nerve fibers develop increased expression of Na+ channels
Na+ channel expression increased
Primary excitatory afferent nerve fiber
Conduction frequency amplified
Na+ = sodium ion. England et al. Neurology 1996;47:272-76. Ochoa et al. Brain. 1980;103:835-853Taylor. Curr Pain Headache Rep. 2001;5:151-161. Sukhotinsky et al. Eur J Pain. 2004;8(2):135-43
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ACTIVITATEA ECTOPICA SIMPTOME - f-ctie de tipul de fibre nervoase:
* fibrele Aβ PARESTEZII, DISESTEZII
* fibrele Aδ DURERE ( “ intepaturi “ )
* fibrele C DURERE ( difuza, “arsura” )
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TRANSMITEREA EFAPTICA
Fibrele nemielinizate sunt separate doar prin cativa μmde axoplasma a cel. Schwann ( d nu permite interactiunea electrica intre 2 fibre alaturate )
Aceasta arhitectura nu se mai mentine cand apar fibre regenerate !
interactiuni electrice intre 2 fibre cu f-ctii independente
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STIMULAREA SIMPATICA
NOCICEPTORII NORMALI NU AU RECEPTORIα-ADRENERGICI
- AFERENTELE NOCICEPTICE PRIMARE LEZATE- NEVROAMELE- GGL. RADACINII DORSALE CU TERMINATII DISTALE LEZATE ( terminatii ale cell. NA din vasele care iriga ggl. migreaza si inerveaza cell. ganglionare insesi, dupa leziuni ale nervului incriminat ; cell. ganglionare exprima receptori α-adrenergici )
DEVIN SENSIBILE LA AGONISTI ADRENERGICI !
DURERE MENTINUTA PRIN MECANISM SIMPATIC
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INFLAMATIA
NU PRODUCE ACTIVITATE ECTOPICA !
ACTIVEAZA CAILE NOCICEPTIVE NORMALE DE LANIVELUL NERVI NERVORUM IN UNELE AFECTIUNI( hernia discala acuta, neuropatia brahiala acuta )
TNFα induce descarcari in aferentele nociceptive primare ( limita intre durerea nociceptiva si durerea neuropatica )
TNFα legare de receptor FOSFORILARE 3 MAPK ( p38 MAPK, JNK, ERK ) in neuronii DRG si in celulele gliale spinale: modificarea act. de semnalizare intracelulara act. genica modificata modificari structurale locale mec. DURERII NEUROPATICE
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MECANISME CENTRALE ALE DURERII NEUROPATICE
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" WIND-UP "
Stimul
Stimul
Fibre nervoase aferente primare Neuronii cornului dorsal
medular
Descarcari repetate de trenuri de stimuli in fibrele de tip C induc descarcari in neuronii cornului dorsal medular la frecvente progresiv crescute
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SENSIBILIZAREA CENTRALA STIMUL-DEPENDENTA
Aβ mecanoreceptor
stimul normal
stimul normal
Leziune nervoasa: transmiterea crescuta nociceptiva conduce la sensibilizarecentrala
fara durere
durere
Normal: activarea fibrelorAβ nu determina activarea neuronior mediatori ai durerii din cornul dorsal
Woolf and Mannion. Lancet 1999;353:1959-1964
Aβ mecanoreceptor
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PIERDEREA CONTROLULUI INHIBITOR IN CORNUL DORSAL
Normal
Leziune
Stimul nedureros sau nociceptiv
Raspuns exagerat la
durere
spre creier
Cai descendente
Local
Cai descendente
Local
spre creier
Woolf and Mannion. Lancet 1999;353:1959-1964
Descarcari spontane
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Activitate sustinuta fibre C
( nociceptiva / neuropatica )
+
“Wind-up” la nivel supraspinal
STATUS NEUROPATIC CRONIC
( rol major: SP, NK, Glu )
* HIPERALGEZIE
* ALODINIE
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Leziunile nn. periferici +
mediatorii sistemici ai inflamatiei
alterari ale excitabilitatii terminatiilor nociceptive ale nervilor lezati si de vecinatate
+ alterari la nivelul cornului posterior medular
* modificari de excitabilitate neuronala (semnalizare intracelulara si activitatea a > 1200 gene )
* pierdere de neuroni GABA-ergici* activare si proliferare microgliala si astrocitara
modificari structurale de tip BOALA NEURODEGENERATIVA
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LEZIUNILE NN. PERIFERICI( TNFα & alte citokine)
NEUROPLASTICITATE
( sprouting fb. mici, act. crescuta in ggl. radacinii dorsale, )cresterea densitatii canalelor de Na+
altereaza semnalul de intrare in S.N.C.
( Glu )
modificari neuroplastice ale structurilor mb. receptoare( cornul posterior m.s. & structuri supraspinale )
* fenomen LTP, alterarea sistemului GABA* expresia canalelor de Na+ ( nr., distributie, structura )
* expresia canalelor de Ca++ N, T, P/Q ( contin prot. α2 – δ )
( Glu, subst. P )
ALTEREAZA PERCEPTIA DURERII
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LEZIUNILE NN. PERIFERICI / RADACINILOR
activitate cu frecventa spontana crescuta in cell. cornului posterior
DURERE DE DEZAFERENTARE
DECONECTAREA CEL. GGL. RADACINII DORSALE de PRELUNGIREA LOR CENTRALA
degenerescenta walleriana a terminatiei centrale ( ex. avulsii radiculare sau de plexuri )
+ fibre non-nociceptive cu Φ mare din cornul posterior sprouting colateral
ALODINIE ( in teritoriul in care s-a pierdut nociceptia )
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DURERILE NEUROPATICE
- LEZIUNILE NN. PERIFERICI:- pierdere de fibre nervoase: hipo / anestezie- focare ectopice pe fb. restante si pe radacinile dorsale:
tulb. subiective: durere- modificari la nivelul neuronilor spinali
* activitate spontana* prag scazut de stimulare: allodinie* cresterea campului de receptie
- MODIFICARI DE TRANSMISIE NERVOASA & SINAPTICA:- remodelarea canalelor axonale de Na (distributie, densitate, tip) → activitate ectopica periferica si radiculara- modificarea activitatii canalelor de Ca tip N si T ( din cornul dorsal medular)- cresterea act. r. Glu ( in cornul dorsal medular ) in neuropatiile cronice prin stimulare aferenta sustinuta + pierderea
controlului inhibitor al GABA activitate sinaptica anormala inducerea si mentinerea hiperexcitabilitatii spinale => durere cronica
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COMPLEXUL MEZENCEFAL (VTA) SISTEM LIMBIC ROL MAJOR in: modularea perceptiei durerii
realizarea comportamentului la durere
subst.P & opioizi endogeni
activarea neuroni DA-ergici ( VTA )
receptori D2 ( D3 & D2 ) in ncc. accumbens ( ε SIST. LIMBIC ) ( interferente cu mediatia 5-HT si Glu/ NMDA )
" ON- PAIN " / " OFF-PAIN "
* activarea sistemelor analgezice ( fazic, tonic )( AGONISTI DOPAMINERGICI D2 EFECTE ANALGEZICE ! )
* reactia comportamentala adecvata la durere si alte solicitari
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SISTEME DESCENDENTE IN S.N.C. DE MODULARE ( sistem descendent noradrenergic, serotoninergic, opioid )
SISTEM MEZOLIMBIC ( DA ) & STRIATUL VENTRAL ( Nc. acc )
faciliteaza reactia la durere / inhiba perceptia durerii- CORTEX FRONTAL & HIPOTALAMUS
- SUBST. CENUSIE PERIAPEDUCTALA
- REG. DORSOLATERALA PONTO-BULBARA ( NA ) & - REG. VENTRO-MEDIALA BULBARA
( nc.magnus raphe, 5-HT )
- FASCICULELE DORSOLATERALE SPINALE
lame I, II, V (corn posterior )
* endorfine receptori enkefalinici, receptori A1* substanta P* NA, receptori α-adrenergici* 5-HT
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LEZIUNI SNC SUPRASPINALE- LEZIUNI BULBARE SI PONTINE LATERALE
* posibil intreruperea cailor de control descendent
- LEZIUNI MEZENCEFALICE* substanta cenusie periapeductala ( ex. migrena )* aria tegmentala ventrala ( B.Parkinson ?, durere cronica - fibromialgia ? )
- LEZIUNI TALAMICE * posibil intreruperea cailor de control descendent* sensibilitate alterata a neuronilor talamici* hiperactivitate a neuronilor talamici
- LEZIUNI CORTICALE
IRMf si PET: DEZAFERENTAREA SENZITIVA
REORGANIZAREA PATTERN DE ACTIVITATEIN TALAMUS & CORTEXUL SOMATO-SENZITIV
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ExemplePeriferic• Nevralgia postherpetica• Nevralgia de trigemen• Neuropatia diabetica• Durerea tabetica• Neuropatia posttraumaticaCentral• Durerea post AVC• Migrena ?• Cluster headache ?Periferic & centralSd. dureros regional complex( CRPS I & II )
Exemple • Durerea din inflamatie • Fracturi• Osteoartrita• Durerea viscerala
postchirurgicala
Exemple • Durerea radiculara• Durerea din cancer• Sindromul de tunel
carpian• B. Parkinson ?• Scleroza multipla ?• Fibromialgia ?
Durerea cu componenta
mixta neuropatica si nociceptiva
Durerea neuropatica
Durere determinata de o leziune sau disfunctie la nivelul
sistemului nervos
Durerea nociceptiva
Durerea determinta de o leziune a anumitor regiuni a corpului tesutul muscular, scheletic,
viscere.
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EVALUARE CORECTA:EVALUARE CORECTA:
DIAGNOSTICULDIAGNOSTICUL DURERII NEUROPATICEDURERII NEUROPATICE
1. ANAMNEZA: 1. ANAMNEZA: " Limbajul durerii "" Limbajul durerii "
2. EXAMENUL CLINIC GENERAL / NEUROLOGIC 2. EXAMENUL CLINIC GENERAL / NEUROLOGIC
3. EXPLORARI SUPLIMENTARE3. EXPLORARI SUPLIMENTARE
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Semne si simptomeDescriere (exemple)
Simptome spontane
– Durere1 Durere lancinanta, sub forma de arsura, sau soc electric.
– Disestezie2 Senzatie dezagreabila anormala (arsura, durere)
– Parestezie2 Senzatie anormala dar fara caracter neplacut (de exemplu furnicaturi)
Simptome evocate
– Allodinie2Perceperea ca durere a unui stimul nedureros
(presiune, caldura)
– Hiperalgezie2 Un raspuns exagerat la un stimul dureros moderat
– Hiperpatie2 Un raspuns intirziat, exagerat la orice stimul dureros
1.Baron. Clin J Pain. 2000;16:S12-S20.2. Merskey H et al. (Eds) In: Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 1994:209-212.
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ISTORICUL DURERIIISTORICUL DURERII
TIPUL, DISTRIBUTIA SI TIPUL, DISTRIBUTIA SI LOCALIZAREA DURERIILOCALIZAREA DURERII
CARACTERUL ACUZELORCARACTERUL ACUZELOR
• e.g. arsura, lovitura, intepaturi… e.g. arsura, lovitura, intepaturi…
• Topografia dureriiTopografia durerii
• Iradiere in alte teritoriiIradiere in alte teritorii
DURATA ACUZELORDURATA ACUZELOR
INTENSITATEA MEDIE A DURERII INTENSITATEA MEDIE A DURERII In ultimele zile/sapt. (0-10)In ultimele zile/sapt. (0-10)
GRADUL DE AFECTARE A GRADUL DE AFECTARE A ACTIVITATII ZILNICE (0-10)ACTIVITATII ZILNICE (0-10)
1. Jensen and Baron. Pain. 2003;102:1-8
IDENTIFICAREA IN ANAMNEZA:IDENTIFICAREA IN ANAMNEZA:11
EXPLORAREA SUPLIMENTARA:EXPLORAREA SUPLIMENTARA:
Expunerea la toxice sau alte terapii Expunerea la toxice sau alte terapii medicale, radiatiimedicale, radiatii
Antecedentele medicale Antecedentele medicale
Utilizarea medicatiei contra dureriiUtilizarea medicatiei contra durerii
Asocierea tulburarilor afective si Asocierea tulburarilor afective si psihologicepsihologice
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ELEMENTELE ESENTIALE IN ISTORICELEMENTELE ESENTIALE IN ISTORIC
modul de apariţie al durerii ( relaţia cu o afecţiune preexistentă sau relaţia cu o afecţiune preexistentă sau cu cu un factor declanşatun factor declanşator )or )
descrierea / caracterizarea durerii
localizarea durerii si iradierea / extinderea sa
evoluţia durerii în timp
starea generala a pacientului
terapiile anterioare
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Scale de evaluare a durerii
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CHESTIONARUL DE DIAGNOSTIC DN4
DUREREA NEUROPATICA IN 4 INTREBARIDUREREA NEUROPATICA IN 4 INTREBARI
– Completat de medic in cabinetCompletat de medic in cabinet
– Se raspunde prin DA ( 1 punct ) sau NU ( 0 puncte)Se raspunde prin DA ( 1 punct ) sau NU ( 0 puncte)
– 2 intrebari despre durere ( max. 7 puncte )2 intrebari despre durere ( max. 7 puncte )
– 2 testari ale sensibilitatii ( max. 3 puncte )2 testari ale sensibilitatii ( max. 3 puncte )
– Scorul pacientului: 0 / 10 Scorul pacientului: 0 / 10 ↔↔ 10 / 10 10 / 10
– Diferentiaza durerea neuropatica de cea nociceptivaDiferentiaza durerea neuropatica de cea nociceptivaSCOR SCOR 4 / 10 : DURERE NEUROPATICA 4 / 10 : DURERE NEUROPATICA
( sensibilitate 62,9% si specificitate 89,9% )( sensibilitate 62,9% si specificitate 89,9% )
DN4: Douleur Neuropathique en 4 questions, Bouhassira et al. 2004
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DISCUTIE CU PACIENTUL1). Durerea are una sau mai multe din urmatoarele caracteristici?
- arsura
- senzatie dureroasa de frig
- descarcari electrice
2). Durerea este asociata in aceeasi zona cu unul sau mai multe dintre urmatoarele simptome
- furnicaturi
- intepaturi
- amorteli
- mancarimi
EXAMENUL CLINIC 3). Durerea este localizata intr-o zona in care examenul clinic releva unul sau
mai multe dintre urmatoarele semne
- hipoestezie la atingere
- hipoestezie la intepatura
4). In zona dureroasa, durerea poate fi provocata sau sporita de:
- atingere
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PENTRU EVALUAREA EFICACITĂŢII PENTRU EVALUAREA EFICACITĂŢII TRATAMENTULUITRATAMENTULUI
PAIN RELIEF SCALE PAIN RELIEF SCALE GLOBAL IMPRESSION OF CHANGE GLOBAL IMPRESSION OF CHANGE
TESTE DE MASURARE A CALITATII VIETII TESTE DE MASURARE A CALITATII VIETII (( scala de 11 puncte, scale specifice: SF-36, NHP sau scala de 11 puncte, scale specifice: SF-36, NHP sau QoL Index ) QoL Index )
In studii clinice: In studii clinice: NNTNNT- - numărul de pacienţi trataţi pentru a numărul de pacienţi trataţi pentru a obtine obtine la unla un pacient o ameliorare a durerii de cel puţin 50% pacient o ameliorare a durerii de cel puţin 50%
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DISTRIBUTIA NERVILOR PERIFERICIDISTRIBUTIA NERVILOR PERIFERICI
Haymaker W et al. Peripheral Nerve Injuries. 1953:40-43.
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Tipuri de neuropatie
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EXAMENUL CLINIC NEUROLOGICEXAMENUL CLINIC NEUROLOGIC
EVALUAREA GLOBALA A INTEGRITATII SN EVALUAREA GLOBALA A INTEGRITATII SN CENTRAL SI PERIFERICCENTRAL SI PERIFERIC
EVALUAREA SISTEMULUI MOTOR EVALUAREA SISTEMULUI MOTOR
EVALUAREA SENSIBILITATIIEVALUAREA SENSIBILITATII
EXAMINAREA SISTEMULUI NERVOS VEGETATIVEXAMINAREA SISTEMULUI NERVOS VEGETATIV
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De ce examenul motilitatii in explorarea durerii neuropatice ?
* diagnostic etiologic: afectiune neurologica cu manifestari multiple
* uneori tulburarile motorii ( dificultati motorii, inabilitate, miscariinvoluntare ) in absenta leziunii cailor motorii pot fi expresia unor tlburari de sensibilitate:
- reactie comportamentala de aparare
- tulburari de sensibilitate proprioceptiva
- tulburari ale somatognoziei
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EXAMENUL MOTILITATIIEXAMENUL MOTILITATII
- Forta musculara- Forta musculara
- Tonus- Tonus
- Troficitate: atrofie, - Troficitate: atrofie, hipertrofie hipertrofie
- Miscari involuntare : - Miscari involuntare : fasciculatii, ticuri, miscari fasciculatii, ticuri, miscari coreice, atetozice, coreice, atetozice, distonie, spasme, tremordistonie, spasme, tremor
- Reflexe- Reflexe
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EXAMENUL SENSIBILITATIIEXAMENUL SENSIBILITATII
- Durere/ sensibilitate dureroasa- Durere/ sensibilitate dureroasa
- Atingere/ sensibilitate tactila- Atingere/ sensibilitate tactila
- Presiune/ sensibilitate barestezica- Presiune/ sensibilitate barestezica
- Sensibilitate proprioceptiva- Sensibilitate proprioceptiva
- Sensiblitatea vibratorie- Sensiblitatea vibratorie
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HIPERALGEZIA: examen la patul HIPERALGEZIA: examen la patul bolnavului bolnavului
TIPUL DE TIPUL DE HIPERALGEZIEHIPERALGEZIE TESTTEST RASPUNS RASPUNS
ASTEPTATASTEPTAT
MECANICA MECANICA INTEPAREINTEPARE
Intepare manuala cu un Intepare manuala cu un ac neascutitac neascutit
Durere ascutita, Durere ascutita, superficialasuperficiala
TERMICA-CALDTERMICA-CALD Atingerea pielii cu un Atingerea pielii cu un obiect la ~45-50°Cobiect la ~45-50°C
Senzatie dureroasa, Senzatie dureroasa, arsuraarsura
TERMICA-RECETERMICA-RECE Atingerea pielii cu agenti Atingerea pielii cu agenti frigorifici (acetona)frigorifici (acetona)
Senzatie dureroasa, Senzatie dureroasa, arsuraarsura
Baron R. Clin J Pain. 2000;16:S12-S20. Jensen and Baron. Pain. 2003;102:1-8
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ALODINIATIPUL DE TIPUL DE ALODINIEALODINIE TESTTEST RASPUNSUL RASPUNSUL
ASTEPTATASTEPTAT
Mecanica staticaMecanica staticaPresiune manuala Presiune manuala usoara asupra usoara asupra tegumentelortegumentelor
Durere surdaDurere surda
MecanicaMecanica
” ” punctata ”punctata ”Intepare usoara manuala Intepare usoara manuala cu un obiect ascutitcu un obiect ascutit
Durere ascutita , Durere ascutita , superficialasuperficiala
Mecanica Mecanica dinamicadinamica
Lovirea pielii cu o perie, Lovirea pielii cu o perie, vata sau material textilvata sau material textil
Durere ascutita, Durere ascutita, arzatoare, arzatoare, superficiala superficiala
Termica- caldTermica- cald Atingerea pielii cu un Atingerea pielii cu un obiect incalzit la ~ 40°Cobiect incalzit la ~ 40°C
Senzatie Senzatie dureroasa, arsuradureroasa, arsura
Termica-receTermica-rece Atingerea pielii cu un Atingerea pielii cu un obiect cu T de ~ 20 °Cobiect cu T de ~ 20 °C
Senzatie Senzatie dureroasa, arsuradureroasa, arsura
Baron R. Clin J Pain. 2000;16:S12-S20. Jensen and Baron. Pain. 2003;102:1-8
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" Elemente - cheie " in examenul sensibilitatii:
* suprafata " anormala " apare mai mare cand examinarea se face din afara spre interior:
- pasul I: testarea se face dinspre interior spre exterior, pentru a delimita zona de deficit senzitiv
- pasul II: testarea din afara spre interior, pentru a delimita zona de fenomene senzitive pozitive ( hiperalgezie, allodinie ), pentru a minimiza durata stimularii dureroase
* tipul de tulburare de sensibilitate si marginile zonei anormale sunt reproductibile pentru durerea neuropatica, la examinari repetate
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EXAMENUL FUNCTIILOR VEGETATIVEEXAMENUL FUNCTIILOR VEGETATIVE
Termoreglare (asimetrie de temperatura)Termoreglare (asimetrie de temperatura)
Reglare vasomotorie (modificari de culoare)Reglare vasomotorie (modificari de culoare)
Sudoratie (modificari ale transpiratiei)Sudoratie (modificari ale transpiratiei)
Reactii pilomotoriiReactii pilomotorii
Modificari trofice (par, unghii, tegumente)Modificari trofice (par, unghii, tegumente)
Alte modificari (ex: hipotensiunea posturala,edeme)Alte modificari (ex: hipotensiunea posturala,edeme)
Bruehl, 1999; DeGowin, 1981.
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De ce examenul tulb. vegetative in durerea neuropatica ?
* pot fi consecinta directa a leziunilor neurologice- o sectiune completa a unui nerv poate produce initial o vasodilatatie ( pierderea tonusului vasoconstrictor ), iar mai tarziu vasoconstrictie ( hipersensibilitatea de denervare a peretelui vascular )
- expresia receptorilor adrenergici la nivelul neuronilor din ggl. radacinii dorsale cu prelungiri lezate, inervate de terminatii simpatice din peretii vaselor locale
* pot fi expresia unor reflexe spinale/ supraspinale la durere- stimularea durereoasa & stimularea mecanoreceptorilor
cu prag scazut pot declansa raspuns vasoconstrictor si sudomotor ( consecinta si nu cauza durerii ! )
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EXAMINARI SPECIFICE DE DIAGNOSTIC:EXAMINARI SPECIFICE DE DIAGNOSTIC: EXAMINARI MOTORIIEXAMINARI MOTORII
Masurarea vitezei de conducere nervoasa ( VCM ) si a Masurarea vitezei de conducere nervoasa ( VCM ) si a amplitudinii potentialului motor amplitudinii potentialului motor testeaza fibrele motorii groase, testeaza fibrele motorii groase, mielinizatemielinizate
Electromiografia (EMG) Electromiografia (EMG) detecteaza si caracterizeaza afectiunile detecteaza si caracterizeaza afectiunile unitatii motorii indiferent daca acestea se datoresc lezarii SN sau unitatii motorii indiferent daca acestea se datoresc lezarii SN sau musculaturiimusculaturii
Stimularea magnetica transcraniana (TCS) Stimularea magnetica transcraniana (TCS) detecteaza detecteaza transmiterea impulsului motor in SNC si identifica eventualele intarzieri transmiterea impulsului motor in SNC si identifica eventualele intarzieri sau blocuri de conduceresau blocuri de conducere
Harrison’s Principles of Internal Medicine, 15th ed, 2002; Olney, 1998.
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EXAMINARI SPECIFICE DE DIAGNOSTICEXAMINARI SPECIFICE DE DIAGNOSTIC EXAMINARI SENZITIVEEXAMINARI SENZITIVE
- Teste de conducere nervoasa senzitiva (VCS)- Teste de conducere nervoasa senzitiva (VCS)• VCS masoara viteza de conducere nervoasa si VCS masoara viteza de conducere nervoasa si
amplitudinea posibila de actiune a fibrelor groase amplitudinea posibila de actiune a fibrelor groase mielinizate senzitive. mielinizate senzitive.
- Testarea senzorială cantitativ (Quantitative sensory testing-QST)
- Microneurografia (MCN)- Microneurografia (MCN)
• MCN determina prezenta impulsurilor ectopice venite MCN determina prezenta impulsurilor ectopice venite de la o singura fibra senzitiva. de la o singura fibra senzitiva.
Dotson, 1997; Harrison’s Principles of Internal Medicine, 14th ed, 1998; Olney, 1998.
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EXAMINARI SPECIFICE DE DIAGNOSTICEXAMINARI SPECIFICE DE DIAGNOSTIC EXAMINARI ALE FUNCTIILOR VEGETATIVEEXAMINARI ALE FUNCTIILOR VEGETATIVE
Variabilitatea frecventei cardiaceVariabilitatea frecventei cardiace
Testarea cantitativa a reflexului Testarea cantitativa a reflexului sudomotor (QSART - Quantitative sudomotor (QSART - Quantitative sudomotor axon reflex test )sudomotor axon reflex test )
Masuratori ale fluxului sanguin: Masuratori ale fluxului sanguin: laser Dopplerlaser Doppler
Cline, 1989; Olney, 1998; Dotson, 1997; Low, 1992, 1993.
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EXAMINARI SPECIFICE DE DIAGNOSTICEXAMINARI SPECIFICE DE DIAGNOSTIC EXAMINARI ALE FUNCTIILOR VEGETATIVEEXAMINARI ALE FUNCTIILOR VEGETATIVE
Photo courtesy of Baron
Temperatura tegumentelor: Temperatura tegumentelor: termografiatermografia
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EXAMINARI SPECIFICE DE DIAGNOSTIC:EXAMINARI SPECIFICE DE DIAGNOSTIC: ALTE TESTEALTE TESTE
" Skin-punch biopsy "" Skin-punch biopsy " biopsia unor zone mici tegumentarebiopsia unor zone mici tegumentare
• Examinarea fibrelor nervoase Examinarea fibrelor nervoase periferice mai mici, mielinizate periferice mai mici, mielinizate sau nemielinizate cu coloratii sau nemielinizate cu coloratii specialespeciale
Reducerea densitatii in neuropatie cu edem al fibrelor
nervoase
Densitate normala
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EXAMINARI SPECIFICE DE DIAGNOSTICEXAMINARI SPECIFICE DE DIAGNOSTIC ALTE TESTEALTE TESTE
Imagistica prin CT, MRI, IRMf;Imagistica prin CT, MRI, IRMf;
• Investigarea prin tehnici Investigarea prin tehnici imagistice a cauzelor posibile, imagistice a cauzelor posibile, centrale sau periferice, ce au centrale sau periferice, ce au declansat neuropatia.declansat neuropatia.
Leziune talamica
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Meyer-Rosberg et al. Eur J Pain. 2001;5:379-389
Simptome asociate cu durerea neuropatica
0 10 20 30 40 50 60 70
inapetenta
anxietate
depresie
tulb. concentrare
ameteli
fatigabilitate
insomnie
% pacienti du durere moderata/severa (n=126)
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EVALUAREA PSIHOLOGICAFactori ce sugereaza necesitate unei evaluari Factori ce sugereaza necesitate unei evaluari psihologice mai atente:psihologice mai atente:
- - prezenta tulburarilor afective sau anxioaseprezenta tulburarilor afective sau anxioase
- - evidentierea abuzului unei substanteevidentierea abuzului unei substante
- - prezenta unei psihozeprezenta unei psihoze
- - evidentierea unei tulburari cognitiveevidentierea unei tulburari cognitive
- - prezenta ideilor suicidaprezenta ideilor suicidarre e
- - urmarirea unor beneficii secundare boliiurmarirea unor beneficii secundare bolii
- probleme ca ostilitate, furie sau tulburari de personalitate- probleme ca ostilitate, furie sau tulburari de personalitate
- - esecuri terapeutice multiple sau prelungiteesecuri terapeutice multiple sau prelungite
- - aprecierea oportunitatii unor terapii agresive invazive aprecierea oportunitatii unor terapii agresive invazive
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CENTRAL SESITIZATION & " WIND-UP "
A. CNS amplifies the peripheral stimulus :
1. the response to nociceptor stimulation become exaggerated and prolonged = HYPERALGESIA
2. stimulation of low threshold primary dynamic afferents = ALLODYNIA
3. pain also beyond the limits of the coresponding lesional area = SECONDARY HYPERALGESIA
B. Long term structural modifications: PAIN MAINTENANCE WITHOUT PERIPHERAL STIMULATION
( peripheral block does not abolish pain any longer )
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PERIPHERAL NEUROPATHIC PAIN
- NERVE and SYNAPTIC TRANSMISSION MODIFICATIONS:- axonal Na channels remodelation (distribution, density, type) → peripheral and radicular ectopic activity- type N and T Ca channels activity modification ( in the spinal dorsal horn )- GluR increased activity ( in the spinal dorsal horn ) in chronic neuropathies by sustained afferent stimulation + loss of GABA inhibitory control abnormal synaptic activity induction and maintainance of spinal hyperexcitability => chronic pain
- LESIONS in PERIPHERAL NN./ CLINICAL EXAMINATION:- loss of nerve fibers: hypo / anesthesia- ectopic foci on the remaining fibers and on the dorsal roots:
* subjective perception: pain- changes in the spinal neurons
* spontaneous activity: hyperalgesia* decreased threshold of stimulation: allodynia* increase of receptive field: secondary hyperalgesia
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PERIPHERAL NEUROPATHIC PAIN
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CENTRAL NEUROPATHIC PAIN
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Surface projections of the 11C-diprenorphine binding potential data of the control mean and the patient viewing the left (Lt.) medial, left lateral, right (Rt.) lateral and right medial surfaces. A marked asymmetry is seen between the left and right lateral surfaces in the patient with less binding on the right cortical surface. An apparent bilateral reduction in binding is identifiable on the medial surfaces of the patient's images in comparison with the control mean. In contrast to the FDG data, reduced 11C-diprenorphine binding is emphasized in the orbitofrontal cortex and in anterior parts of the cingulate cortex (regions with high opioid receptor density).>>
Willoch F. et al., Am J Neuroradiology 20:686-690 (4 1999)
CORTICAL AREAS INVOLVED IN PAIN PERCEPTION AND MODULATION of BEHAVIOUR TO PAIN
( expression of opioid receptors )
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1 Mild
2 Moderate
3 Severe
AspirinAspirin
ParacetamolParacetamol
NSAIDSNSAIDS
± Adjuvant± Adjuvant
CodeinCodeinee
DihDihyydrocodeindrocodeinee
OxOxiicodoncodonee
TramadolTramadol
± Adjuvant± Adjuvant
MorphineMorphine
HydromorphoneHydromorphone
MethadoneMethadone
FentanylFentanyl
OxicodonOxicodon
± Adjuvant± Adjuvant
NOCICEPTIVE PAIN TREATMENT WHO scale
VAS SCORE: 1-3
VAS SCORE: 4- 6
VAS SCORE: 7- 10
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NEUROPATHIC PAIN
HYPEREXCITABILITY STATE of SOMATOSENSORY NERVOUS SYSTEM OF
NOCICEPTION !
RESPONSE TO CONVENTIONAL ANALGETICS - UNCONCLUSIVE
THERAPEUTIC RESPONSE WITH DRUGS WHICH DECREASE THE STATE OF HYPEREXCITABILITY
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Pharmacologic agents used for the treatment of neuropathic pain
Antidepressive Amitriptiline, bupropion, clomipramine, desipramine, imipramine, nortriptyline, etc
Anticonvulsi
vants
Carbamazepine, clonazepam, gabapentin, pregabalin, lamotrigine, phenitoin, etc.
Opioids Fentanyl, morphine, oxicodone, tramadol, etc
NSAIDS Ibuprofen, sulindac, etc
Other drugs Clonidine, lidocaine, mexiletine, etc
Topic agents Local anaesthetics, capsaicin
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Pregabalin modulates neurons in hyperexcitability state
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OTHER DRUGS IN NEUROPATHIC PAIN
• ANTIARYTHMICS - MEXILETINE– Without significant improvement in 4 trials
• CAPSAICINE ( TOPIC )– Dyscrepancy of results, does not seem to be advantageous in
neuropathic pain
• NMDA ANTAGONISTS– MEMANTINE – not-convincing efficacy– DEXTROMETORPHAN – pain improvement in 2 small trials
• LEVODOPA- efficacy- 1 RCT class II
• NSAIDS – limited or absent efficacy
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FINAL RECOMMENDATIONS• Drugs with EBM efficacy ( level A ): TCAs, duloxetine, venlafaxine,
gabapentin, pregabalin, opioids, tramadol
• TCAs seem to have the best NNT – but the trials are not systematic • FIRST LINE: TCAs / gabapentin/ pregabalin
• SECOND LINE: duloxetine, venlafaxine – preffered in patients with cardiovascular risk
• LINE 2/3- opioids and lamotrigine ( level B )
• NON-CERTAIN / ABSENCE of EFFICACY: * capsaicine, mexiletine, OXC, SSRI, topiramate ( level A )* memantine, minaserin, clonidine topic ( level B )
• LIMITED EFFICACY: CBZ ( important adverse reactions ! )
• LIMITED DATA: dextrometorphan, levodopa