Phantom Pain: Mechanisms

Pain Refresher Course, ASEAPS, Singapore 2013

Troels Staehelin Jensen, MD, Ph.D
Dept. of Neurology &
Danish Pain Research Center
Aarhus University Hospital, Denmark
Phantom Pain Mechanisms:
Peripheral
Peripheral sensitisation
Spontaneous neuronal activity
DRG abnormal activity
Spinal
Central sensitization
Spontanous neuronal activity
Wind up like pain
S1
Insula
ACC
Amygdala
Wind up like pain
Spread of central sensitisation
Supraspinal
Cortical reorganisation
Anxiety
Catastrophising
Sensitization following inflammation
Neuronal hyperexcitability
Lowering of threshold
Recruitment of silent nociceptors
Abnormal temporal summation (wind-up)
Aftersensations
Normalization when inflammation subsides
Inflammation
Spinal cord
Spinal cord
Spinal cord
Spinal cord
Central sensitization following nerve injury
Nuronal hyperexcitability
Lowering of threshold
Recruitment of silent nociceptors
Abnormal temporal summation (wind-up)
Aftersensations
Maladaptive changes
Nerve injury
Spinal cord
Spinal cord
Spinal cord
Postamputation pain
Phantom Pain: Peripheral mechanisms
Spontaneous activity in neuromas
DRG abnormal activity
Spinal
Central sensitization
Spontanous neuronal activity
Abnormal temporal summation (wind-up)
Amputation Phantom Pain Phantom Limb
Phantom Pain:
Supraspinal mechanisms
Davis et al. Nature, 1995
Fig in Lancet Neurol.
Reorganisering efter amputation:
Hjerneomrder vandrer
Catastrophizing and phantompain:
A set of negative emotional and
cognitive processes resulting in:
Magnification of pain related symptoms
Rumination about pain
Helplessnes and pessimistic thoughts
Vase et al. 2011
Helplessness
Rumination
Magnification
Phantom Pain supraspinal mechanisms
Cortical reorganisation (Flor et al. 1995)
Anxiety (Shukla et al. 1982)
Catastrophizing (Jensen et al. 2010; Vase et al. 2011)
Amputation Phantom Pain Phantom Limb
Flor et al. 2006
Thalamus
Postamputation pain mechanisms
Sensory abnormality
L 1
T4
L 1
T4
Spinal cord
Spinal cord
Spinal cord
STT
Sensory abnormality
Phantomlimb pain proposal:
Integrative action in the
Nervous system (Sherrington 1906)
Tapping stump triggers wind-up like pain
Dorsal horn sensitization spreads to brain
Cortical plasticity
Activation of cingulate cortex and insula
Attentional changes
Increased descending facilitation
Cerebral excitation Cerebral excitation
Wind-up like pain
Mechanism of Postamputation Pains
Peripheral
Brain
Phantom limb
Pain
Spinal
Implication for mangement ?
Postamputation pains: Risk factors
Reactivation of previous pains
(Riddoch 1941, Nathan 1965, Katz and Melzack
1990)
Severe preamputation pain
followed by severe postamputation
pain (Jensen et al. 1984,1985, Nikolajsen et al.
1997)
Pain sensitivity before amputation Pain sensitivity before amputation
correlates to early pain (Nikolajsen et al
2000).
Stump sensitivity correlates to
phantom pain (Nikolajsen et al 2000).
Amputation associated with
Hypersensitivity in stump area
Common risk factors for chronicity
Biological
Genetic
Preinjury pain
Longlasting and intense pains
Specific tissue damage ?
Psychological
Bio
Psycho
Psychological
Psychological stress (avoidance)
Anxiety
Catastrophizing
Social
Low education
Unemployment
Social
Phantom pain: Can it be prevented ?
Endpoints:
Stump Pain
Phantom pain
Opioid consumption
Preamputation pain
during epidural Block
Nikolajsen et al. Lancet 1997
After bolus in OPT
After bolus During cont
infusionn
P
a
i
n

i
n
t
e
n
s
i
t
y

(
0
-
1
0
0
)
0
20
40
60
80
100
Control group
Blockade group
Prevention of phantom pain:
Epidural morphine/bupivacaine
18 hrs. before amputation
Pain amputation 1 week after
amputation
Block Control
Phantom
pain
(0-100)
75%
VAS:20
69%
VAS:9
Stump
pain
(0-100)
VAS:0 VAS:4
Opioid
use (mg)
0 0
Pain 12 months
after amputation
Nikolajsen et al. Lancet 1997
PhantomPain Treatment
Evidence Pharmacology:
Effect of opioids, NMDA antagonist,
anticonvulsants, antidepressants and
calcitonin is uncertain
Morphine, gabapentine, ketamine
Provides short-term pain relief
Good quality trials with long follow-up,
sufficent sample size is needed. sufficent sample size is needed.
Neuropathic pain
Cause
Comorbidity
Phantom Pain: Pharmacological Management
TCAs
SNRI
-2- agents
Topical lidocaine,
topical capsaicin, opioids
Tramadol, opioids
Oxcarbazepine,
lacosamide, lamotrigine
Peripheral Central
Cannabinoids
Contraindication
Cost
Thanks to all collaborators at DPRC:
Birgitte Brandsborg, Erisela Querama, Lene Vase, Lone Nikolajsen, Anders D
Kristensen, Hanne Gottrup, Nanna Finnerup, Cathrine Baastrup, Henriette Kristensen, Hanne Gottrup, Nanna Finnerup, Cathrine Baastrup, Henriette
Klit, Lise Gormsen, Astrid Terkelsen, Annette T. Mller, Helle O. Andersen,
Camilla Maersk-Mller, Anne Hansen, Lene Christensen, Casper Skau-
Madsen, Kaare Brinck, Paal Karlsson
Phantom Pain Mechanisms
Interaction between
Peripheral and brain mechanisms ?
Catastrophizing associated with
greater thermal temporal
summation in volunteers.
Edwards et al. 2006
Mechanical wind up reduced by
ketamine in phantomlimb pain
Nikoljsen et al. 1996
Amputation PhantomPain PhantomLimb
Nikoljsen et al. 1996