Clinical and Applied Physiology Program

1
Clinical and Applied Physiology Program at
the Department of Neuroscience University of
Turin Medical School Turin, Italy www.personalweb
.unito.it / fabrizio.benedetti
2
Symbols
molecules
RECEPTORS
Drugs
Therapeutic effects
Negative effects
3
evolution
4
Egbert et al. (1964) N Engl J Med 270
825 Post-operative pain
Pre-operative phase
1st post-operative day
1.187
Pain intensity
26 mg
Morphine intake
1.735
Pain intensity
38 mg
Morphine intake
5
Thomas (1987) Br Med J 294 1200 Cough Sore
throat Cold Abdominal pain Back
pain Giddiness Leg pain Headache Tiredness Chest
pain Nasal congestion Muscular pain Earache Painfu
l arm Breast pain Neck pain
Consultation
Two weeks later
This treatment will certainly make
you better
64
who got better
I am not sure that this treatment
will have an effect
39
who got better
6
1st model Placebo administration
2nd model Open-hidden paradigm
This treatment will certainly make
you better
7
Placebo effect Context effect
Words
Sight
Touch
Medical treatment
Dummy treatment
Smell
8
Unconscious
Conscious
PSYCHOSOCIAL CONTEXT
Conditioned response

• COGNITION
• Expectation
• Belief
• Trust
• Hope

Conditioned stimulus
Effect
Unconditioned stimulus (e.g. drug)
9
ICD-10 of the World Health Organization
Placebo-related effects
A00-B99 Certain infectious and parasitic diseases
C00-D48 Neoplasms
D50-D89 Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism Some immune mediators (IL-2, IFN-gamma, leukocytes.....) (Giang et al 1996 Goebel et al 2002)
E00-E90 Endocrine, nutritional and metabolic diseases Some hormones (growth hormone, cortisol.......) (Benedetti et al. 2003)
F00-F99 Mental and behavioural disorders Major depression (Leuchter et al. 2002 Mayberg et al. 2002) Anxiety (Benedetti et al 2003, Petrovic et al 2005) DBS-induced emotions (Benedetti et al 2004)
G00-G99 Diseases of the nervous system Pain (Levine et al 1978 Benedetti 1996 Amanzio Benedetti 1999 Petrovic et al 2002 Wager et al 2004 Lorenz et al 2005 Zubieta et al 2005) Parkinsons disease (de la Fuente-Fernandez et al 2001 Benedetti et al 2004)
H00-H59 Diseases of the eye and adnexa
H60-H95 Diseases of the ear and mastoid process
I00-I99 Diseases of the circulatory system Autonomic control of heart (Pollo et al 2003 Lanotte et al 2005)
J00-J99 Diseases of the respiratory system Drug-induced respiratory depression (Benedetti et al 1998, 1999)
K00-K93 Diseases of the digestive system Irritable bowel syndrome (Lieberman et al 2004 Vase et al 2005)
L00-L99 Diseases of the skin and subcutaneous tissue
M00-M99 Diseases of the musculoskeletal system and connective tissue
N00-N99 Diseases of the genitourinary system
O00-O99 Pregnancy, childbirth and the puerperium
P00-P96 Certain conditions originating in the perinatal period
Q00-Q99 Congenital malformations, deformations and chromosomal abnormalities
R00-R99 Symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified
S00-T98 Injury, poisoning and certain other consequences of external causes
V01-Y98 External causes of morbidity and mortality
Z00-Z99 Factors influencing health status and contact with health services
U00-U99 Codes for special purposes
10
Colloca and Benedetti (2005) Nature Rev.
Neurosci. 6 545-552
11
30
Pain tolerance (minutes)
25
20
15
DAY1 DAY2 DAY3 DAY4 DAY5
Zubieta et al. (2005) J. Neurosci. 25 7754 7762
MOR
MOR
PLA
NAL
Amanzio Benedetti (1999) J. Neurosci. 19 484-94
12
Remifentanil
Placebo
ACC
PAG
Pons
Medulla
Petrovic et al. (2002) Science 295 1737-40
13
Colloca and Benedetti (2005) Nature Rev.
Neurosci. 6 545-552
14
3
Pain intensity (NRS)
2
1
0
PROGLUMIDE CCK-A (CCK-1) CCK-B (CCK-2) receptor an
tagonist
Control
Nocebo- induced anxiety
Benedetti et al. (1997) Pain 71 135-140
15
Placebo suggestions
Nocebo suggestions
Colloca and Benedetti (2005) Nature Rev.
Neurosci. 6 545-552
16
(No Transcript)
17
Nocebo suggestions
Colloca and Benedetti (2005) Nature Rev.
Neurosci. 6 545-552
18
ICD-10 of the World Health Organization
Placebo-related effects
A00-B99 Certain infectious and parasitic diseases
C00-D48 Neoplasms
D50-D89 Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism Some immune mediators (IL-2, IFN-gamma, leukocytes.....) (Giang et al 1996 Goebel et al 2002)
E00-E90 Endocrine, nutritional and metabolic diseases Some hormones (growth hormone, cortisol.......) (Benedetti et al. 2003)
F00-F99 Mental and behavioural disorders Major depression (Leuchter et al. 2002 Mayberg et al. 2002) Anxiety (Benedetti et al 2003, Petrovic et al 2005) DBS-induced emotions (Benedetti et al 2004)
G00-G99 Diseases of the nervous system Pain (Levine et al 1978 Benedetti 1996 Amanzio Benedetti 1999 Petrovic et al 2002 Wager et al 2004 Lorenz et al 2005 Zubieta et al 2005) Parkinsons disease (de la Fuente-Fernandez et al 2001 Benedetti et al 2004)
H00-H59 Diseases of the eye and adnexa
H60-H95 Diseases of the ear and mastoid process
I00-I99 Diseases of the circulatory system Autonomic control of heart (Pollo et al 2003 Lanotte et al 2005)
J00-J99 Diseases of the respiratory system Drug-induced respiratory depression (Benedetti et al 1998, 1999)
K00-K93 Diseases of the digestive system Irritable bowel syndrome (Lieberman et al 2004 Vase et al 2005)
L00-L99 Diseases of the skin and subcutaneous tissue
M00-M99 Diseases of the musculoskeletal system and connective tissue
N00-N99 Diseases of the genitourinary system
O00-O99 Pregnancy, childbirth and the puerperium
P00-P96 Certain conditions originating in the perinatal period
Q00-Q99 Congenital malformations, deformations and chromosomal abnormalities
R00-R99 Symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified
S00-T98 Injury, poisoning and certain other consequences of external causes
V01-Y98 External causes of morbidity and mortality
Z00-Z99 Factors influencing health status and contact with health services
U00-U99 Codes for special purposes
19
Parkinsons disease
Decrease of raclopride binding
de la Fuente-Fernandez et al. ( 2001) Science
293 1164-6
20
(No Transcript)
21
P r e p l a c e b o
P o s t p l a c e b o
22
Firing rate (spikes/s)
30 s
Benedetti et al. (2004) Nature Neurosci, 7
587-588
23
1st model Placebo administration
2nd model Open-hidden paradigm
This treatment will certainly make
you better
24
Benedetti et al. (1995) Lancet 346 1231
25
hidden drug
Benedetti et al. (1995) Lancet 346 1231
26
computer
Open injection
Hidden injection
BUPRENORPHINE
TRAMADOL
KETOROLAC
METAMIZOL
open
open
open
open
hidden
hidden
hidden
hidden
0
Pharmacodynamic effect
-1
Pain reduction
Psychological effect
-2
-3
Benedetti et al (1995) Lancet 346 1231 Amanzio
et al. (2001) Pain 90205-15 Colloca et al
(2004) Lancet Neurol. 3 679-684
27
ICD-10 of the World Health Organization
Placebo-related effects
A00-B99 Certain infectious and parasitic diseases
C00-D48 Neoplasms
D50-D89 Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism Some immune mediators (IL-2, IFN-gamma, leukocytes.....) (Giang et al 1996 Goebel et al 2002)
E00-E90 Endocrine, nutritional and metabolic diseases Some hormones (growth hormone, cortisol.......) (Benedetti et al. 2003)
F00-F99 Mental and behavioural disorders Major depression (Leuchter et al. 2002 Mayberg et al. 2002) Anxiety (Benedetti et al 2003, Petrovic et al 2005) DBS-induced emotions (Benedetti et al 2004)
G00-G99 Diseases of the nervous system Pain (Levine et al 1978 Benedetti 1996 Amanzio Benedetti 1999 Petrovic et al 2002 Wager et al 2004 Lorenz et al 2005 Zubieta et al 2005) Parkinsons disease (de la Fuente-Fernandez et al 2001 Benedetti et al 2004)
H00-H59 Diseases of the eye and adnexa
H60-H95 Diseases of the ear and mastoid process
I00-I99 Diseases of the circulatory system Autonomic control of heart (Pollo et al 2003 Lanotte et al 2005)
J00-J99 Diseases of the respiratory system Drug-induced respiratory depression (Benedetti et al 1998, 1999)
K00-K93 Diseases of the digestive system Irritable bowel syndrome (Lieberman et al 2004 Vase et al 2005)
L00-L99 Diseases of the skin and subcutaneous tissue
M00-M99 Diseases of the musculoskeletal system and connective tissue
N00-N99 Diseases of the genitourinary system
O00-O99 Pregnancy, childbirth and the puerperium
P00-P96 Certain conditions originating in the perinatal period
Q00-Q99 Congenital malformations, deformations and chromosomal abnormalities
R00-R99 Symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified
S00-T98 Injury, poisoning and certain other consequences of external causes
V01-Y98 External causes of morbidity and mortality
Z00-Z99 Factors influencing health status and contact with health services
U00-U99 Codes for special purposes
28
Cognitive impairment
Benedetti et al (2006) Pain 121 133-144
29
P l a c e b o
buprenorphine
1.2
1.15 mg/patient
1.0
0.8
-33.8
0.76 mg/patient
buprenorphine request
0.6
Buprenorphine intake/patient (mg)
0.4
0.2
0
0
10
70
20
30
40
50
60
Pollo et al. (2001) Pain 93 77-84
Hours from surgery
30
Is mind as real as matter?
Symbols
molecules
RECEPTORS
Drugs
Therapeutic effects
Negative effects
31
Clinical and Applied Physiology Program at
the Department of Neuroscience University of
Turin Medical School Turin, Italy www.personalweb
.unito.it / fabrizio.benedetti
NEUROLOGY Bruno Bergamasco Leonardo
Lopiano Innocenzo Rainero Giovanni
Asteggiano Luisella Tarenzi Elena Torre
NEUROPHYSIOLOGY Luana Colloca Antonella
Pollo Sergio Vighetti
SURGERY Giuliano Maggi Caterina Casadio Anna
Arslanian
PSYCHOLOGY Martina Amanzio Claudia Arduino Sara
Costa
RESPIRATORY PATHOPHYSIOLOGY Sergio Baldi
NEUROSURGERY Michele Lanotte Antonio Melcarne