clinical diagnosis and treatment of neuropathic pain mudr.rudolf Černý, csc dept of neurology 2nd...
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Clinical diagnosis and Clinical diagnosis and treatment of NEUROPATHIC treatment of NEUROPATHIC
painpain
MUDr.Rudolf Černý, CScMUDr.Rudolf Černý, CScDept of NeurologyDept of Neurology
2nd School of Medicine2nd School of MedicineCharles University in PragueCharles University in Prague
Definitions Definitions Pain definition IASP Pain definition IASP :: “unpleasant sensorial and “unpleasant sensorial and
affective affective experienceexperience, caused by actual or , caused by actual or potential tissue damage, ore described in terms potential tissue damage, ore described in terms of such a damage”of such a damage”
Pain is always subjective experience, Pain is always subjective experience, psychological psychological elaboration ofelaboration of : : nociceptive afferencenociceptive afference dysfunction of the nervous systemdysfunction of the nervous system stored experience (memory trace, learned pain stored experience (memory trace, learned pain
behavior)behavior) psychosocial dysfunctionpsychosocial dysfunction
Neuropathic pain = Neuropathic pain = generated by the nervous generated by the nervous system system
Components of chronic painComponents of chronic pain
1)1) nociceptivenociceptive - tissue damage, local - tissue damage, local inflammation, activation of nociceptor endingsinflammation, activation of nociceptor endings
2)2) neuropatneuropathhicic - pain is generated by - pain is generated by peripheral or central nervous system peripheral or central nervous system Projected pain into the respective innervation area. Projected pain into the respective innervation area.
Primary NS damage is not a indispensable Primary NS damage is not a indispensable conditioncondition
3)3) psychogenicpsychogenic - transformation of non painful - transformation of non painful perception, affection and cognitive processes into perception, affection and cognitive processes into pain experiencepain experience
4)4) socialsocial subconscious behavior pattern in failing coping with subconscious behavior pattern in failing coping with
work load or family problemswork load or family problems conscious purposeful behavior with the aim to conscious purposeful behavior with the aim to
receive compensation claims, rent or social benefitsreceive compensation claims, rent or social benefits
Criteria of NPCriteria of NP
evidence of NS lesionevidence of NS lesion neuroanatomical correlation of the pain neuroanatomical correlation of the pain
perception (sensory disturbance in perception (sensory disturbance in distribution of radicular dermatome, area distribution of radicular dermatome, area nervina etc…)nervina etc…)
evidence of sensorial disturbance abnormityevidence of sensorial disturbance abnormity chronic conditions – 3- 6 monthschronic conditions – 3- 6 months low efficacy of analgesicslow efficacy of analgesics
Epidemiology of NPEpidemiology of NP
25% patients in 25% patients in centers for Pain treatment centers for Pain treatment Populational prevalence estimated about 1 % !Populational prevalence estimated about 1 % !
like Epilepsylike Epilepsy pprevalence increases with age, above 70 nearly revalence increases with age, above 70 nearly 50% reffer 50% reffer
some symptoms of some symptoms of NP !NP ! Permanent complication in peripheral nerve injuries Permanent complication in peripheral nerve injuries
cca 5%cca 5% MMetabolic polyneuropathyetabolic polyneuropathy - cca - cca 50% diabetics elder 50% diabetics elder
then 60 yearsthen 60 years NS INS Infectionsnfections - - cca 30%cca 30% cases of HIV, cases of HIV, neuroboreliosis,neuroboreliosis,
herpes zoster herpes zoster Central NP Central NP ::
syringomyelia syringomyelia - - 75% cases 75% cases 30% in MS30% in MS 88% ischemic strokes% ischemic strokes
Pathophysiology of NPPathophysiology of NP
complex event – NS adaptation to chronic pain complex event – NS adaptation to chronic pain stimulationstimulation
functional adaptation – morphological functional adaptation – morphological restructuralizationrestructuralization
all level of neuraxis involvedall level of neuraxis involved result – result – sensitizationsensitization (periph. and central) (periph. and central)
increased sensitivity to painful stimuliincreased sensitivity to painful stimuli painful perception of innocuous stimulationpainful perception of innocuous stimulation spontaneous pain perception WITHOUT peripheral spontaneous pain perception WITHOUT peripheral
stimulationstimulation
cause-adaptaption-cause-adaptaption-mechanismus-symptomesmechanismus-symptomes
primary causative eventprimary causative event chronic nociceptor stimulachronic nociceptor stimulationtion– neurogenn– neurogennic inflammationic inflammation NS dysfunctionNS dysfunction idiopathic cases (erythromelalgia, SFN)idiopathic cases (erythromelalgia, SFN)
adaptationadaptation changes in PN fibers, sympatical and thermic fibers switched to changes in PN fibers, sympatical and thermic fibers switched to
nociception nociception central sensitization – posterior horn, thalamus, SMA, cingulumcentral sensitization – posterior horn, thalamus, SMA, cingulum
molecular mechanismsmolecular mechanisms Na channels, NMDA receptors, GABA receptors, microglia Na channels, NMDA receptors, GABA receptors, microglia
activationactivation neuronal mechanisms – expansion of receptive fieldsneuronal mechanisms – expansion of receptive fields changed activity of PH interneurons, thalamus – Thunberg grillchanged activity of PH interneurons, thalamus – Thunberg grill
Mechanismy NBMechanismy NB
hyperaktivace nociceptorů a vláken C, A deltahyperaktivace nociceptorů a vláken C, A delta funkční změny DRG, zadní roh, STTfunkční změny DRG, zadní roh, STT
molekulární, receptorové, synaptickémolekulární, receptorové, synaptické strukturální změnystrukturální změny
synapsesynapse populace interneuronů ZRpopulace interneuronů ZR
talamustalamus druhá vrátka, přesun k hyperaktivitě talamic relay druhá vrátka, přesun k hyperaktivitě talamic relay
neuron STTneuron STT porucha integrace tepelných x bolestivých vjemů v porucha integrace tepelných x bolestivých vjemů v
mediálním jádře - CBmediálním jádře - CB cortex – nábor nových areícortex – nábor nových areí
Peripheral Peripheral sensitizationsensitization NociceptorsNociceptors
recruitment of silent, mechano-insenzitive recruitment of silent, mechano-insenzitive nociceptorsnociceptors
acid sensing ion channelsacid sensing ion channels heat activated ion channelsheat activated ion channels CGRP, sbst PCGRP, sbst P against - anti-inflammatory mediators (ACh, against - anti-inflammatory mediators (ACh,
anandamid)anandamid) Peripheral nerve fibersPeripheral nerve fibers
expression of Na channelsexpression of Na channels high frequency firing C-fibershigh frequency firing C-fibers eecctopic source of action potentials in axon topic source of action potentials in axon
membranemembrane
Central Central sensitizationsensitization
DRG cells :DRG cells : 3 funkční stavy řízené K kanálem (tonic, plateau = 3 funkční stavy řízené K kanálem (tonic, plateau =
amplifikace, rhytmic firing = filtrace)amplifikace, rhytmic firing = filtrace) remodelaceremodelace sprouting Abeta zakončenísprouting Abeta zakončení
„„hyperalgesic“ neuronhyperalgesic“ neuron spinotalamická dráhaspinotalamická dráha
parabrachiální – „normální“ akutní bolestparabrachiální – „normální“ akutní bolest spino-retikulo-talamická – PAG – chronická bolestspino-retikulo-talamická – PAG – chronická bolest
TalamusTalamus KortexKortex
Molecular mechanismsMolecular mechanisms new channels new channels
Na, Ca alfa2 deltaNa, Ca alfa2 delta expression of new membrane receptorsexpression of new membrane receptors
sbst P, TRPV1, NK1, alfa2 adrenoreceptorsbst P, TRPV1, NK1, alfa2 adrenoreceptor mimiccroglia activationroglia activation paradoxical effects of glycin releaseparadoxical effects of glycin release macrophage activation – TNF alfa – Schwann macrophage activation – TNF alfa – Schwann
cell – NGF expressioncell – NGF expression changes of membrane properties of HEALTHY changes of membrane properties of HEALTHY
nerve fibers !nerve fibers ! efferent sympatical activationefferent sympatical activation
Paradoxical excitation by inhibitory Paradoxical excitation by inhibitory
mediators - GABA, Glycinmediators - GABA, Glycin !! !!
peripheral nerve fiber lesion - chronic peripheral nerve fiber lesion - chronic stimulation of lamina I PH Neuronsstimulation of lamina I PH Neurons
decrease of potassium transporter decrease of potassium transporter concentration KCC2 concentration KCC2 intracellular accumulation of Cl intracellular accumulation of Cl
with increase intracellular KCL with increase intracellular KCL concentration GABA a glycin produce concentration GABA a glycin produce EXCITATORY PSPs !!EXCITATORY PSPs !!
PH adaptation to chronic PH adaptation to chronic nociceptive stimulationnociceptive stimulation STT neurons can have 3 functional states:STT neurons can have 3 functional states:
1.1. tonic discharge – respond by series AP to perif. stimulustonic discharge – respond by series AP to perif. stimulus2.2. rhythmic bursting – AP firing outlast the stimulusrhythmic bursting – AP firing outlast the stimulus3.3. plateau potential – spontaneous AP firing WITHOUTplateau potential – spontaneous AP firing WITHOUT
stimulation – hyperalgesic neuronstimulation – hyperalgesic neuron less then 10% neurons is normally in state 3, after less then 10% neurons is normally in state 3, after
sensitization process most of them !!sensitization process most of them !! transition of functional statestransition of functional states
is regulated by ratio of metabotrope receptors:is regulated by ratio of metabotrope receptors: NMDA + GABAb = antagonistic regulation of a common NMDA + GABAb = antagonistic regulation of a common
potassium channel of type Kir3potassium channel of type Kir3
Secondary hyperalgesia Secondary hyperalgesia is CENTRAL phenomenonis CENTRAL phenomenon
Summary Summary
Symptoms of NPSymptoms of NP
SpontaneousSpontaneous painpain pparesthesia, dysesthesiaaresthesia, dysesthesia
EvokedEvoked hyperalgesiahyperalgesia allodyniaallodynia painpain
SpontaneousSpontaneous pain pain
Lancinating painLancinating pain – – neuralgicneuralgic
Paroxysms of Paroxysms of sharp, stabbing sharp, stabbing pain pain
Peripheral Peripheral nerve:nerve:Ectopic activation , Ectopic activation , abnormal Na abnormal Na channelschannels
continuous dull continuous dull painpain
Sensitization of Sensitization of peripheral peripheral nociceptorsnociceptors
KauzalgiaKauzalgia burning painburning pain Sympatically Sympatically maintained painmaintained pain
ALODYNIA – innocuous ALODYNIA – innocuous stimulus produces painstimulus produces pain
Dynamical mechanic Dynamical mechanic A.A.
Touch stimulation by Touch stimulation by cotton swab drawn on the cotton swab drawn on the skinskin
Aß fibers Aß fibers switch to switch to nociception nociception
Static mechanic A.Static mechanic A. Blunt touch by fingerBlunt touch by finger Senzibilizace Senzibilizace C C nociceptorůnociceptorů
Cold A.Cold A. Cold stimulus perceived as Cold stimulus perceived as painfulpainful
Cold fibers C evoke Cold fibers C evoke STT activitySTT activity
Temporal Temporal summation summation
wind up – by repeated wind up – by repeated stimulusstimulus
PH = PH = NMDA NMDA activity activity increasedincreased
HYPERALGESIAHYPERALGESIA
MechanicalMechanical Increased pin prick Increased pin prick sensitivitysensitivity
increased increased sensitivity ofsensitivity of Aδ Aδ fibersfibers
ThermicThermic Pain with 46 C Pain with 46 C stimulusstimulus
vaniloid vaniloid receptor receptor sensitizedsensitized
ColdCold 25 C stimulus 25 C stimulus painfulpainful
C fibers C fibers sensitizedsensitized
Lower threshold for pain stimulation
Classification Classification of of NPNP
Peripheral x CentralPeripheral x Central Symmetrical x Asymmetrical NPSymmetrical x Asymmetrical NP EtiologicalEtiological Symptomatological – mechanism basedSymptomatological – mechanism based
Peripheral cause of NP – most frequentPeripheral cause of NP – most frequent
Focal neuropathiesFocal neuropathies Compresive neuropathy (carpal tunel)Compresive neuropathy (carpal tunel) Discogennic radix compressionDiscogennic radix compression Peripheral nerve injuryPeripheral nerve injury Postherpetic neuralgiaPostherpetic neuralgia Mononeuropathia multiplexMononeuropathia multiplex
Difusse polyneuropathies :Difusse polyneuropathies : Metabolic (diabetes, etylismusMetabolic (diabetes, etylismus, amyloid polyneuropathy, hypotyreosis, , amyloid polyneuropathy, hypotyreosis,
hypovitaminosis B)hypovitaminosis B) Infection (HIV, borrelióza, herpes zoster, CMV)Infection (HIV, borrelióza, herpes zoster, CMV) Toxic (arsen, thalium, isoniazid, nitrofurantoin, metronidazol, chloramfenikol, Toxic (arsen, thalium, isoniazid, nitrofurantoin, metronidazol, chloramfenikol,
cytostatics)cytostatics) Hereditary senso-motor neuropathiesHereditary senso-motor neuropathies
Complex regional pain syndrome (RSD)Complex regional pain syndrome (RSD) Cranial neuralgias (trigeminal, glossofaryngeal…)Cranial neuralgias (trigeminal, glossofaryngeal…) Chronic vertebrogennic algic syndromeChronic vertebrogennic algic syndrome, postlaminectomic syndromes, postlaminectomic syndromes
Spinal cord disorders with NP Spinal cord disorders with NP
Multiple sclerosisMultiple sclerosis Spinal cord injurySpinal cord injury Myelopathy : Myelopathy :
Metabolical (hypovitaminoza B12, diabetes)Metabolical (hypovitaminoza B12, diabetes) VascularVascular SyringomyeliaSyringomyelia
CompressionCompression
Central NPCentral NP
Thalamic (central) pain:Thalamic (central) pain: Ischemic stroke Ischemic stroke Thalamic hemorrhageThalamic hemorrhage
Multiple sclerosisMultiple sclerosis Arnold Chiari malformationArnold Chiari malformation Neurodegeneration Neurodegeneration
Parkinson diseaseParkinson disease Alzheimer diseaseAlzheimer disease MSA, SCAMSA, SCA
Phantom painPhantom pain
Typical character of NPTypical character of NP
Continuous spontan, chronic pain - dullContinuous spontan, chronic pain - dull Evoked pain by external and internal stimuli - Evoked pain by external and internal stimuli -
lancinatinglancinating Always hypoesthesia, pain co localized Always hypoesthesia, pain co localized Pain is always projective with typical distributionPain is always projective with typical distribution Temporal summation of pain by repeated Temporal summation of pain by repeated
stimulationstimulation After-sensations, MitempfindungAfter-sensations, Mitempfindung Trophic changes – sympatic nerves over activityTrophic changes – sympatic nerves over activity
Work up of NPWork up of NP Clinical examClinical exam
symptom classificationsymptom classification sensory examinationsensory examination
distribution !distribution ! evoked symptoms of pain?evoked symptoms of pain? semiquantitasemiquantitattive examination (von Frey filaments, warm, ive examination (von Frey filaments, warm,
cold)cold) Laboratory and imagingLaboratory and imaging
etiological possibilitiesetiological possibilities Electrophysiological examinationElectrophysiological examination
assessment of NS functionassessment of NS function EMG – only thick, non-pain fibers evaluated !!EMG – only thick, non-pain fibers evaluated !! evoked potentials - SSEP and MEP – long tracts of spinal evoked potentials - SSEP and MEP – long tracts of spinal
cordcord QST, QSMAT, LEP, microneurography, R-R interval QST, QSMAT, LEP, microneurography, R-R interval
variabilityvariability
Small fiber Small fiber neuropathyneuropathy
SFNSFN
PN –80% of fibers C and A deltaPN –80% of fibers C and A delta routine examination cannot detect functionroutine examination cannot detect function EMG assess only thick fibers of light touch EMG assess only thick fibers of light touch
and vibrationand vibration clinical picture:clinical picture:
thermic hypoesthesiathermic hypoesthesia low threshold of thermic painlow threshold of thermic pain causalgia – „burning feet“causalgia – „burning feet“
SFNSFN
usually part of peripheral neuropathy usually part of peripheral neuropathy symptoms:symptoms: DM, etylic, HIVDM, etylic, HIV hereditary – Charcot Marie Toothhereditary – Charcot Marie Tooth
isolated SF affection possibleisolated SF affection possible SKIN BIOPSYSKIN BIOPSY EMG excludes general neuropathyEMG excludes general neuropathy LEPs abnormalLEPs abnormal
SKIN BIOPSYSKIN BIOPSY in SFN in SFN
117 patients 117 patients with NP in with NP in legslegs
44 with 44 with normal EMGnormal EMG
but: reduction but: reduction of nerve of nerve endings endings denzity in denzity in skin !!skin !!
imunofluorescence – Ab against PGP 9,5
Small x Large fiber neuropathySmall x Large fiber neuropathy
Erythromelalgia - example of SFNErythromelalgia - example of SFN
primary x secondary (DM, myeloproliferative dis.)primary x secondary (DM, myeloproliferative dis.) atacks:atacks:
red, hot, burning feetred, hot, burning feet VAS 4-10/10VAS 4-10/10 pain increase by warmpain increase by warm
mikrovascular a-v shunts in skinmikrovascular a-v shunts in skin termoregulatory hyperperfusiontermoregulatory hyperperfusion nutritive hypoperfusion, hyperkinetic hypoxynutritive hypoperfusion, hyperkinetic hypoxy
small fiber neuropathysmall fiber neuropathy increased sweating, EMG normal orincreased sweating, EMG normal or in 1/3 axonal neuropathyin 1/3 axonal neuropathy
Primary ErythromelalgiaPrimary Erythromelalgia
AD inheritanceAD inheritance painfull peripheral neuropathypainfull peripheral neuropathy zvýšenou citlivost na námahu a tepelné zvýšenou citlivost na námahu a tepelné
podnětypodněty peripheral cyanosisperipheral cyanosis manifesting form childhoodmanifesting form childhood point mutation of Na1,7 channel point mutation of Na1,7 channel chromozom 2q31-32 (gen SCN9A v r. 2004)chromozom 2q31-32 (gen SCN9A v r. 2004) memmbrane hyperexcitability of peripheral memmbrane hyperexcitability of peripheral
nerve fibersnerve fibers
Sympatically maintained painSympatically maintained pain
not a disease but pathophysiologal not a disease but pathophysiologal mechanismmechanism
part of NP symptomspart of NP symptoms no specific parameter from clinic or laboratory!no specific parameter from clinic or laboratory! typical symptomstypical symptoms
cold pressure testucold pressure testu burning, badly localized painburning, badly localized pain trophical changestrophical changes vasoparalysisvasoparalysis
Sympatically maintained painSympatically maintained pain
S. hyperactivity in peripheral nerve lesions:S. hyperactivity in peripheral nerve lesions: expression of adrenoreceptor in nerve expression of adrenoreceptor in nerve
membranemembrane synapses of S. efferent with peripheral fiberssynapses of S. efferent with peripheral fibers DiagnosisDiagnosis
ANS exam - HRV, Ewing testANS exam - HRV, Ewing test gold standard – effect of S. blockadegold standard – effect of S. blockade
TTherapy – alfa blocherapy – alfa blockerskers (prazosin, (prazosin, klonidin, tizanidin), S. ganglia blockingklonidin, tizanidin), S. ganglia blocking
Postherpetic neuralgiaPostherpetic neuralgia DR ganglionitis – VZVDR ganglionitis – VZV acute pain at least 20%, 9-15% after 1 month, 2-5% after 1 yearacute pain at least 20%, 9-15% after 1 month, 2-5% after 1 year age age >> 60-70 year prevalence 50-75% ! 60-70 year prevalence 50-75% ! risks for PHN:risks for PHN:
female genderfemale gender age over 50age over 50 trigeminus- sacral rootstrigeminus- sacral roots intensity of rash, hemorrhagic pustulasintensity of rash, hemorrhagic pustulas
all types of NP – contin. bunirng, attacks of lancinating painall types of NP – contin. bunirng, attacks of lancinating pain typical dynamic mechanical allodyniatypical dynamic mechanical allodynia secondary hyperalgesia exceeding the original exanthema !secondary hyperalgesia exceeding the original exanthema ! Therapy – resistant!Therapy – resistant!
acute phase = acute phase = acycloviracyclovir + carbamazepin + opioids + carbamazepin + opioids chronic phase – anticonvulsiveschronic phase – anticonvulsives + local – capsaicin + opioids + local – capsaicin + opioids
Central PainCentral Pain
1906 Déjerine-Roussy – thalamic 1906 Déjerine-Roussy – thalamic syndromesyndrome
incomplete lesions, 1,5 - 8% incomplete lesions, 1,5 - 8% strokesstrokes
Etiology :Etiology : lacunar infarctionlacunar infarction, aart. , aart.
thalamogeniculatae thalamogeniculatae other = hemorrhage, MS plaque, other = hemorrhage, MS plaque,
gliosisgliosis rare = tumor, trauma, abscessrare = tumor, trauma, abscess
Topic of CPTopic of CP
everywhere in STTeverywhere in STT parietal pseudothalamic syndromeparietal pseudothalamic syndrome POSTEROLATERAL THALAMUSPOSTEROLATERAL THALAMUS posterior arm of capsula internaposterior arm of capsula interna dorsolateral medulladorsolateral medulla spinal cord, particularly cervical spinal cord, particularly cervical
and CC regionand CC region
Pathogenesis of CPPathogenesis of CP
disinhibition of thalamic relay neurons of disinhibition of thalamic relay neurons of STTsSTTs
posterolateral (VPL) Th nucleus and insulposterolateral (VPL) Th nucleus and insulaa denervation hypersensitivity, increased denervation hypersensitivity, increased
NMDA activity and NA channels expressionNMDA activity and NA channels expression deaferentation cortical paindeaferentation cortical pain somatosensoric cortex reorganisationsomatosensoric cortex reorganisation expansion of receptive fields (PET, SPECT)expansion of receptive fields (PET, SPECT) disturbance of central inhibitiondisturbance of central inhibition abnorm LEP x normal SSEPabnorm LEP x normal SSEP Thunberg grilThunberg gril
Character of CPCharacter of CP
dull dull ((sharpsharp))
deep deep ((superficialsuperficial)) burning (icy) burning (icy) paroxysmparoxysmss of lancinating pain of lancinating pain
spontaneousspontaneous provokedprovoked
typical is combination of several pain typestypical is combination of several pain types intensity > 50%VASintensity > 50%VAS provocation of painprovocation of pain : :
peripheral stimulationperipheral stimulation physical and psychogenic stressorsphysical and psychogenic stressors
Character of CPCharacter of CP
pain intensitypain intensity DOES NOT CORRELATE with DOES NOT CORRELATE with topical deficit !topical deficit !
pain evolves within weeks or months foll. pain evolves within weeks or months foll. stroke stroke
hemiparesis usually regressed at this timehemiparesis usually regressed at this time CP can be „healed“ by subsequent strokeCP can be „healed“ by subsequent stroke very unpleasant – suffering, strong affective very unpleasant – suffering, strong affective
componentcomponent depressions, suicidium not rare!!depressions, suicidium not rare!!
Sensory disturbance in CPSensory disturbance in CP
• always present hemi – quadrant distributionalways present hemi – quadrant distribution• can be small part -can be small part - ulnar ridge of the arm ulnar ridge of the arm, ,
cheiro-oral syndrome cheiro-oral syndrome • protopatic character (termoalgic, protopatic character (termoalgic,
propriocepce)propriocepce)• epicritical sensations spared (2 points,light epicritical sensations spared (2 points,light
toMuch, grafestesia, stereognosia)toMuch, grafestesia, stereognosia)• paresthesia, dysestesiaparesthesia, dysestesia• hyperalgesia, alodyniahyperalgesia, alodynia• atypical sensations: after sensations, atypical sensations: after sensations,
MitempfindungMitempfindung• syringomyelie disociated thermoalgic syringomyelie disociated thermoalgic
anestesia with normal touchanestesia with normal touch
Wallenberg syndromeWallenberg syndrome
PICA ischemiaPICA ischemia dorsolateral infarctiondorsolateral infarction ipsilateral face hypoesthesia, crossed ipsilateral face hypoesthesia, crossed
body hypoesthesiabody hypoesthesia ipsilateral bulbar palsyipsilateral bulbar palsy ipsilateral cerebellar ataxiaipsilateral cerebellar ataxia peripheral vestibular failureperipheral vestibular failure NO hemiparesis !NO hemiparesis !
Bilateral thalamic stroke in Bilateral thalamic stroke in T2 T2
weighted MRIweighted MRI
Syringomyelia, Arnold ChiariSyringomyelia, Arnold Chiari
SyringomyeliaSyringomyelia
Therapy of NPTherapy of NP
Complex + CombinedComplex + Combined
Treatment :Treatment :1.1. underlying diseaseunderlying disease2.2. NP symptoms by combination ofNP symptoms by combination of
analgesicsanalgesics anticonvulsiveanticonvulsivess antidepreantidepresssivessives
3.3. locallocal4.4. invasive proceduresinvasive procedures5.5. physical treatmentphysical treatment6.6. psychoterapypsychoterapy
Treatment planTreatment plan
Realistic – better life quality, complete Realistic – better life quality, complete pain relieve in minority of cases !pain relieve in minority of cases !
(„clinically relevant“ pain intensity decrease 45-60%, pain elimination („clinically relevant“ pain intensity decrease 45-60%, pain elimination max. 10%)max. 10%)
Measurable goals !Measurable goals ! Pain diary, pain drawing, consumption of Pain diary, pain drawing, consumption of
pain pillspain pills Informed consent – better treatment Informed consent – better treatment
adherenceadherence
AnalgesicsAnalgesics• Variable, but lower effect in comparison to nociceptive Variable, but lower effect in comparison to nociceptive
pain !!pain !!• WHO „Pain ladder“ is validWHO „Pain ladder“ is valid• but – opioid use in non-malignant painbut – opioid use in non-malignant pain
• walk on mine field !walk on mine field !• Possible substances: Possible substances: • dose acc effect, combinations possibledose acc effect, combinations possible
• paracetamol up 4 g/day, hepatotoxicityparacetamol up 4 g/day, hepatotoxicity• NSAID - better COX2 preferential (meloxicam, NSAID - better COX2 preferential (meloxicam,
nimesulid)nimesulid)• tramadol up 400 mg/daytramadol up 400 mg/day• dihydrocodein sustained release max 2x120mgdihydrocodein sustained release max 2x120mg• morphin SR 2x30-120 mgmorphin SR 2x30-120 mg• transdermal opiodstransdermal opiods
• Synergic action of fixed combination:Synergic action of fixed combination:• paracetamol 325mg-tramadol 50mg (Zaldiar) paracetamol 325mg-tramadol 50mg (Zaldiar)
NNT=3! NNT=3!
AntidepresantsAntidepresants
EBM proved – MEBM proved – Meta analysis eta analysis > > 5000 patients 5000 patients Efficacy inEfficacy in 40-70% 40-70% NNT 2-3, SSRI 6 and more!NNT 2-3, SSRI 6 and more! Analgesis Analgesis is not dependentis not dependent on antidepre on antidepresssive sive
effect effect :: good analgesia in pat. who don't score for Dep.!!good analgesia in pat. who don't score for Dep.!! effect starts early - effect starts early - 1-10 days1-10 days total dose is lowtotal dose is low increased activity of descending pain inhibiting increased activity of descending pain inhibiting
pathways (noradrenalin, serotonin) pathways (noradrenalin, serotonin)
AnticonvulsantsAnticonvulsants
Similar pathogenetic traits in pain sensitization Similar pathogenetic traits in pain sensitization and epileptogenesis and epileptogenesis
Analgetic effect proved in animal and RCT Analgetic effect proved in animal and RCT studies as wellstudies as well
But not in all antiepileptics !But not in all antiepileptics ! I. vs. III. generation anti-EP :I. vs. III. generation anti-EP :
similar efficacysimilar efficacy new drugs:new drugs:
better tolerance, less interaction, no hepatic inductionbetter tolerance, less interaction, no hepatic induction phpharmakoeconomicsarmakoeconomics
AnticonvulsantsAnticonvulsants• carbamazepincarbamazepin – sharp lancinating pain (PHN, TN) – sharp lancinating pain (PHN, TN)
• slow up titration ! , max 1200 mg/dslow up titration ! , max 1200 mg/d• cave toxoalerg.exanthema, central toxicitycave toxoalerg.exanthema, central toxicity• hepatic enzyme inductor – many interactions hepatic enzyme inductor – many interactions
• gabapentingabapentin – well tolerated, RCT proved efficacy in DPN, PHN, TN – well tolerated, RCT proved efficacy in DPN, PHN, TN• 1200-2400 mg, no metabolism, no interactions !1200-2400 mg, no metabolism, no interactions !
• clonazepam, valproate clonazepam, valproate • Back-up possibilities: Back-up possibilities: more SE and interactions slow titration is and interactions slow titration is
a rule!a rule!• lamotrigine lamotrigine 50-100-400mg (rash, central toxicity, blocks 50-100-400mg (rash, central toxicity, blocks
metabolism of valproate )metabolism of valproate )• topiramate topiramate 50-100-400mg (central toxicity, leukopenia, nefrolithiaza)50-100-400mg (central toxicity, leukopenia, nefrolithiaza)• phenytoinphenytoin 2x100mg (nausea, vertigo, bradykardia, heart conduction 2x100mg (nausea, vertigo, bradykardia, heart conduction
blocker, gingival hyperplasia, potentn hepatic enzyme inductor)blocker, gingival hyperplasia, potentn hepatic enzyme inductor)
Pharmacotherapy of Pharmacotherapy of
painpain
Na channels blocking
Ca channels blocking
Descendant inhibition enhancement
Local treatmentLocal treatment
local anesthetics – „lidocain patch“local anesthetics – „lidocain patch“ adhesive plasters, creams, local adhesive plasters, creams, local
injectionsinjections capsaicincapsaicin – Zostrix – Zostrix
sbst P agonist, analg. through destruction of C fiber sbst P agonist, analg. through destruction of C fiber endings endings
PHNPHN local forms of NSAIDlocal forms of NSAID
Adjuvant treatmentAdjuvant treatment
CortiCorticosterocosteroidsids MyorelaxanciaMyorelaxancia Vitamins BVitamins B Thioctic acidThioctic acid
ImportantImportant ! !
treat not only NP, but also BYSTANDER pain:treat not only NP, but also BYSTANDER pain: vertebral pain due to failed movement regimevertebral pain due to failed movement regime movement apparatus – pain form shortened movement apparatus – pain form shortened
tendons, musclestendons, muscles complication of immobility, sphincter functionscomplication of immobility, sphincter functions disorders of sleep and depression !!disorders of sleep and depression !!
Invasive treatmentInvasive treatmentAlgesiology, Center of painAlgesiology, Center of pain local nerve blockadeslocal nerve blockades epidural anesthesiaepidural anesthesia
single blockadesingle blockade long terms catheters (mo+steroids)long terms catheters (mo+steroids)
Spinal cord stimulationSpinal cord stimulation electrical stimulation of Post.Tractselectrical stimulation of Post.Tracts very potent modality in resistent NPvery potent modality in resistent NP
Last resort – pain surgeryLast resort – pain surgery destruction avoideddestruction avoided stimlation methods – motor cortex stimul in intractable stimlation methods – motor cortex stimul in intractable
deafferentation paindeafferentation pain
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