1. פיסיולוגיה מורחב 08-9 Somatosensory System and Pain
פיסיולוגיה מורחב
Somatosensory System
and Pain
lecture 8: Phantom limb and other chronic pain
Prof. Marshall Devor, Ph.D.
Dept. of Cell & Animal Biology and
Center for Research on Pain
Institute of Life Sciences
Hebrew University of Jerusalem

2. descending control phantom prototypical “neuropathic pain”
Mind-body problem: “phantom sensation the best possible proof of the existence of the eternal soul. If an arm can survive physical destruction, why not the whole person?”
Admiral Lord Nelson (died Battle of Trafalgar, 1805)

3. stump pain
phantom pain

4. telescoping key distinctions phantom - phantom pain
stump pain, allodynia
variable onset/ persistence
individual variability
movement, telescoping

5. Plasticity of body schema: reference of sensation from face and chest
into the phantom
Chronholm 1953

6. median n. section
D3 amputation >

7. Map distortion enhanced in patients with PLP Flor, Birbaumer
… does remapping enhance pain,
or does pain enhance remapping ?

8. Nerve injury  somatotopic remapping (DH, DCN, thalamus & SS cortex)
Devor & Wall 1981
delete follicle  neighboring
barrels expand van der Loos

9. df: “neuropathic pain” is pain associated with injury or dysfunction of the nervous system
“The paradox of neuropathic pain”: …nerve injury should dull sensation, not enhance it !
spontaneous pain
pain on movement &
deep palpation
allodynia/hyperalgesia
hyperpathia

10. * central sensitization Chung model hypothesis:
(CNS amplification of evoked & spontaneous afferent impulse activity)

11. 2003 European survey on chronic pain
n >46,000 )telephone survey(
16 European countries (including Israel)
Adults (18 years old or older)
sponsored by Mundipharma
Criterion for "Chronic pain"
Pain for > 6 months duration
Pain within the past month
Pain at least several times a week
Pain intensity >5/10
Breivik et. EJP ‘05

12. Overall European Prevalence(n=46,394) 19% report "chronic pain"
Pain – there's a lot of it !
Overall European Prevalence(n=46,394) 19% report "chronic pain"
(%)
(%)
(n=46,394)
Breivik et. EJP ‘05

13. How often does it hurt?
67% of sufferers report experiencing chronic pain all the time
Frequency – Israel– (n=322)
כמה פעמים בשבוע כל יום כל הזמן
Breivik et. EJP ‘05

14. Main types of chronic pain
headache incl. migraine
backache & sciatica
arthritis (esp. OA)
chronic abdominal pain
diffuse musculoskeletal (fibromyalgia)
neuropathies (shingles (PHN), diabetes, trauma…
~5% of total, but most refractory, costly)
Breivik et. EJP ‘05

15. What is the origin of the nerve impulses
that are felt as a phantom limb ?

16. “neuromatrix”
R. Melzack
dorsal
root
ganglion
nerve end
neuroma

17. Following axotomy ectopic burst firing develops at the
nerve
end
neuroma
Following axotomy ectopic burst firing develops at the
nerve injury site….
Wall & Gutnick ‘74
Devor & Govrin-
Lippmann ‘78

18. Nystrom & Hagbarth ‘81

19. DRG
peripheral
nerve
Matsuda et al. 1981

20. Following axotomy, ectopic burst firing develops at the nerve injury site….
and in the DRG
(Wall & Devor ‘83)

21. Ectopic hyperexcitability in 10 afferent neurons is important for neuropathic pain, but what causes the ectopia ??
Liu et al. 2000

22. “Phenotype” of sensory neurons is closely regulated to ensure appropriate excitability and stimulus selectivity
NGF, BDNF, NT3,
GDNF
spike activity ?

23. Na+-ch immuno-labeling at chronic injured axon end
Devor et. 1989
Neuropathy (axonopathy, demyelination) alters the phenotype (behavior) of sensory neurons:
protein trafficking
NGF, BDNF, NT3,
GDNF
spike activity ?
neuroma

24. X Axonopathy (and demyelination ?) alters the
phenotype of sensory neurons:
gene expression
Waxman et ‘94
Nav1.3
control
NGF, BDNF, NT3,
GDNF
DRG soma
spike activity ?
Chung et ‘02
axotomy Na-ch
upregulation X

25. NGF, BDNF, NT3,
GDNF
Boucher et al
spike activity ?

26. nerve/plexus block spinal block phantom “neuromatrix” DRG central
sensitization
phantom
“neuromatrix”
DRG
spinal block
emergent pain rare (<1/23)
(PLP “always” gone
Tessler & Kleiman ’94;
Boas, Satav personal comm.)
PLP eliminated in ca. 50%
of patients (Birbaumer et.J.Neurosci’97)
nerve/plexus block

27. פיסיולוגיה מורחב Somatosensory System and Pain
lecture 8: Phantom limb and chronic pains
Prof. Marshall Devor, Ph.D.
Dept. of Cell & Animal Biology and
Center for Research on Pain
Institute of Life Sciences
Hebrew University of Jerusalem

28. how much neuroma ?
how much DRG ?
25%
75%
Liu et al. 2000