Dipartimento di Neuroscienze, Università degli Studi di Torinoe

Istituto Nazionale di Neuroscienze (INN), Torino

www.personalweb.unito.it / fabrizio.benedettiwww.ist-nazionale-neuroscienze.unito.it

Placebo

Improvement

Spontaneousremission

Regression tothe mean

Biases

Detectionambiguity

Unidentifiedco-interventions

Psychosocial-psychobiologicalfactors

Pavlovianconditioning

Expectation

Rewardmechanisms

Anxietymechanisms

PLACEBO RESPONSE

IMPROVEMENT IN THE PLACEBO GROUP

Placebo effect = Context effect

Medical treatmentDummy treatment

COGNITION• Expectation• Belief• Trust• Hope

Conditioned stimulus

Unconditioned stimulus (e.g. drug)

Conditioned response

EffectEffect

UnconsciousConscious

Therapeutic effects

Negative effects

Benedetti (2008) Ann Rev Pharmacol Toxicol 48: 33-60

IFN-, IL-2 5-HT1B-1D 5-HT re-uptake D2-D3 CCK-A/B -opioid -adrenergic

immuno sumatriptan anti anti CCK narcotic -blockersuppressive depressant parkinsonian antagonist

Psychosocial context

D r u g s

e x p e c t a t i o na n d / o r c o n d i t i o n i n g

Analgesia andcardiovascularsystem

Hyperalgesia

Parkinson

DepressionHormonalresponsesImmune

responses

Analgesia andrespiratorycenters

Benedetti (2008) Annu Rev Pharmacol Toxicol 48: 33-60

??

Benedetti et al. (1995) Lancet 346: 1231

hidd

en d

rug

Benedetti et al. (1995) Lancet 346: 1231

0

Pain

reduct

ion

BUPRENORPHINE TRAMADOL KETOROLAC METAMIZOL

open openopen openhidden hiddenhidden hidden

-1

-2

-3

Open injection Hidden injection

computer

Pharmacodynamic effect

Psychological effect

Benedetti et al (1995) Lancet 346: 1231Amanzio et al. (2001) Pain 90:205-15Colloca et al (2004) Lancet Neurol. 3: 679-684

TRIAL Met#2 (Colloca and Benedetti, Nature Rev Neurosci 6: 545-552, 2005)

Is metamizol (300 mg) effective in post-thymectomy pain?

Open metamizol injection group (N=10)

Hidden metamizol injection group (N=10)Informed consent “You will receive metamizol but you don’t know when”Double blind

Pai

n in

ten

sity

(N

RS

)

0 1 2 3 4 5 60

2

4

6

8

10

Pai

n in

ten

sity

(N

RS

)

0

2

4

6

8

10

Open injection of metamizol

Hidden injection of metamizol

hours

www.personalweb.unito.it / fabrizio.benedettiwww.ist-nazionale-neuroscienze.unito.it

NEUROFISIOLOGIA

Antonella PolloLuana CollocaSergio Vighetti

PSICOLOGIA

Martina AmanzioClaudia ArduinoElisa Carlino

NEUROLOGIA

Leonardo LopianoInnocenzo RaineroGiovanni Asteggiano

CHIRURGIA

Giuliano MaggiCaterina CasadioAnna Arslanian

NEUROCHIRURGIA

Michele LanotteAntonio Melcarne

Dipartimento di Neuroscienze, Università degli Studi di Torinoe

Istituto Nazionale di Neuroscienze (INN), Torino