Il problema del dolore nell`amputato

Il problema del dolore
nell’amputato
Cesare Bonezzi
Centro di Ricerca cin Fisiopatologia e Terapia del dolore
Fondazione Salvatore Maugeri
In one study, probably the largest field survey
performed in Europe, a questionnaire
containing 62 questions was filled in by 537
out of 1,088 amputees. Of the amputees who
responded, 14.8% were pain free, 74.5% had
phantom limb pain, 45.2% had stump pain
and 35.5% had a combination of both.
Kern U, Busch V, Rockland M, Kohl M, Birklein F.
[Prevalence and risk factors of phantom limb pain and phantom
limb sensations in Germany. A nationwide field survey].
Schmerz. 2009;23:479–488.
Seventeen years after the war between Iraq
and Iran, 64% of 200 soldiers who had lost
limbs during this war suffered from phantom
pain, 32% from phantom movement pain,
while 24% suffered from stump pain.
Ebrahimzadeh MH, Fattahi AS, Nejad AB. Long-term
follow-up of Iranian veteran upper extremity amputees
from the Iran-Iraq war (1980-1988). J Trauma. 2006;61:
886–888.
Meccanismi patogenetici del dolore
Buonocore
Central post stroke pain
Dolore in
un’area di
perdita delle
sensibilità allo
stimolo caldo e
doloroso
After injury to nociceptor neurons, increases in
transcription or altered trafficking of sodium channels as
wellas a reduction in potassium channels increases
membrane excitability sufficiently so that action potentials
are generated spontaneously (ectopicactivity)
Dolore irradiato
nel territorio di
innervazione
dove sono
presenti deficit
del sistema
somatosensoriale
NON SOLO NEUROPATICO
• (17 pts with stump problem from a total of
139 amputees)
• Bursitis and soft tissue inflammation in 10
patients
• Bone abnormalities: osteophytes or fracture
(4), bone marrow edema (3)
• Two asumptomatic neuromas
Foisneau-Lottin A. et al.: Bursitis, adventitious bursa, and bone marrow
edema in tibial stumps: the contribution of magnetic resonance imaging to
the diagnosis and management of mechanical stress complication. Arch Phys
Med Rehabil 2003: 84; 770-777
Perdita di discriminazione tra
Tocco, pressione, pizzico, stretta
SENSIBILIZZAZIONE
WDRN spinali
Allodinia ed iperalgesia
secondarie
Allargamento del campo recettoriale
Dolore riferito
di origine
somatica
LA DIAGNOSI CLINICA
• IRRADIATO
• RIFERITO
IL TEMPO ED I CAMBIAMENTI DEI
MECCANISMI
Small fiber neuropathy
Length dependent
C fiber
Possible
Central
sensitization
Small fiber neuropathy
Non-Length dependent
C fiber
Possible
Central
sensitization
Small fiber neuropathy
Non-Length dependent
deafferentation
Central
Origin of pain
C fiber
Clifford J. Woolf and Michael W. Salter: Neuronal Plasticity: Increasing the Gain in
Pain SCIENCE VOL 288 9 JUNE 2000
Causato da fattori pre-esistenti
Deafferentazione
Sofferenze tissutali dell’arto
ischemiche
infettive
traumatiche
Causato dall’amputazione
Lesione nervosa-neuroma
Lesioni tissutali del moncone
ischemiche
algodistrofiche
infettive
chirurgiche
Causato da nuovi fattori
Patologie neurologiche
“a monte”
Lesioni tissutali “a monte”
infiammatorie
degenerative
traumatiche
Dolore episodico alla mano in forma di senso di
contrazione delle prime due dita
Brush allodynia
Tinel signs with pain in the handfingers
RNM con processo infiammatorio
osseo
Foisneau-Lottin A. et al.: Bursitis, adventitious bursa, and bone marrow
edema in tibial stumps: the contribution of magnetic resonance imaging to
the diagnosis and management of mechanical stress complication. Arch Phys
Med Rehabil 2003: 84; 770-777
• (17 pts with stump problem from a total of
139 amputees)
• Bursitis and soft tissue inflammation in 10
patients
• Bone abnormalities: osteophytes or fracture
(4), bone marrow edema (3)
• Two asumptomatic neuromas
Phantom Limbs: Neuroplastic Phenomena
Ramachandran’s hypothesis: phantom limb caused by
reorganization of the somato-sensory cortex
following amputation
Amputee feels a touch on his face and also on his
phantom limb (due to their proximity on
somatosensory cortex)
Amputee with chronic phantom limb
pain gets relief through visual feedback:
view in mirror of his intact hand
unclenching as seen in mirror box
34
FIGURE 10.23 The places on
Tom’s body where touches
elicited sensations in his
phantom hand. (Based on
Ramachandran & Blakeslee,
1998.)
35
Il dolore fantasmatico
LA TERAPIA
Analgesici – meccanismi patogenetici
A. MODULA
gli impulsi afferenti
nocicettivi
A B
B. AMPLIFICA
gli impulsi A-delta e C
(sensibilizzazione spinale,
c.d. componente
neuropatica)
3
ANALGESICI AD AZIONE
RECETTORIALE
Steroidi, Fans, Cox2
GENERA gli impulsi
del dolore nocicettivo
1
2
FARMACI AD AZIONE SINAPTICA
A. azione modulatoria
indipendentemente dalla presenza di
sensibilizzazione spinale:
paracetamolo e oppiacei
B. azione modulatoria mediata dal
sistema inibitorio spinale o
discendente:
amitriptilina, duloxetina, clonazepam
C. azione modulatoria diretta
presinaptica:
Alfa2 delta ligandi (gabapentin e
pregabalin)
D. azione A+ B: tapentadolo
ANALGESICI AD AZIONE SULLA
FIBRA (ECTOPIA)
Amitriptilina, Carbamazepina,
Oxcarbazepina
GENERA gli impulsi del dolore
neuropatico periferico
TERAPIA DEI MECCANISMI
PATOGENETICI DEL DOLORE
Meccanismi
recettorali
Meccanismi
ectopici
✴Farmaci ad azione sulla
ipersensibilità recettoriale
(antinfiammatori)
✴Blocchi anestetici/cortisonici
Meccanismi
spinali
✴Cifo/Vertebroplastica
✴ Interventi sul disco
✴Termolesioni a
radiofrequenza
✴Farmaci modulanti la
trasmissione sinaptica (oppiodi)
✴Farmaci che riducono
l’ipersensibilità spinale
✴Neurostimolazione
✴Farmaci ad azione sulla
ipersensibilità ectopica
(bloccanti i canali del sodio)
✴Blocchi anestetici/cortisonici
✴Termolesioni a
radiofrequenza
✴Neurostimolazione
Medication trials
• TCA’s and sodium channel blockers are currently considered
the drug treatments of choice for neuropathic pain, but a
2004 study of 39 patients demonstrated no benefit of TCA’s
over placebo in PLP after 6 weeks. (Robinson et al 2004)
• One study showed that mexiletine produced pain relief in 18
of 31 patients with PLP. (Davis 1993)
• Opioids (MST) produced pain relief in 42% of patients and
showed evidence of reduced cortical reorganization in 12
patients with PLP. (Huse E 2001)
• There have been mixed results in studies using memantine to
treat chronic pain, but it may be successful in treating PLP if
initiated in early post-amputation period. (Hackworth, et al
2008)
Adjuvant therapies
• TENS has reduced PLP in multiple placebo controlled
trials.
• Mirror box therapy: persons with amputated limb
use either a mirror or mirror box to reflect an image
of the intact limb. It is hypothesized that this works
by preventing cortical restructuring.
• One RCT of 22 patients showed 100% of patients
with MBT showed decreased pain after 4 weeks.
(Chan BL 2007)
Mirror box therapy
Neuromodulazione chimica spinale
POMPA
PERSISTALTICA
TOTALMENTE
IMPIANTABILE
CATETERE
SUBARACNOIDEO
Neuromodulazione elettrica spinale
Pacemaker
Elettrodo peridurale
Peripheral nerve
stimulation : median nerve
Dynamic Mechanical Allodynia in
and out of the scar
49
LEAD INTRODUCTION
It has been shown that BoNT-A treatment
can reduce peripheral sensitization by inhibiting
the release of several neuronal signaling markers
including substance P, glutamate, calcitonin
gene-related peptide (CGRP) in autonomic
vascular nerve terminals, and reducing cfos
gene expression. Direct action of BoNT-A on
sensory neurons in vivo inhibiting the release not
only of glutamate but also of substance P and
CGRP from peripheral terminals of nociceptive
fibers was demonstrated in a previous study.