Il sistema cannabinergico e il controllo del dolore

Costa Barbara “Il sistema cannabinergico e il controllo del dolore”
“Il sistema cannabinergico e il controllo del dolore”
THC
CB1
CP55,940
WIN55,212
CB1
CB1
“Il sistema cannabinergico e il controllo del dolore”
SR141716
CB1 knockout mice
“Il sistema cannabinergico e il controllo del dolore”
“Il sistema cannabinergico e il controllo del dolore”
“Il sistema cannabinergico e il controllo del dolore”
Pain relief
without
“high”?????
“Il sistema cannabinergico e il controllo del dolore”
CB1 agonists
selective for
peripheral
receptors
Selective CB2
agonists
“Il sistema cannabinergico e il controllo del dolore”
CB2
CB2
“Il sistema cannabinergico e il controllo del dolore”
From Zhang et al., 2003
From Maresz et al., 2005
“Il sistema cannabinergico e il controllo del dolore”
From Monory and Lutz, 2005
“Il sistema cannabinergico e il controllo del dolore”
CB1 agonists
selective for
peripheral
receptors
FAAH
inhibitors or
AMT blockers
Selective CB2
agonists
“Il sistema cannabinergico e il controllo del dolore”
ANANDAMIDE
“Il sistema cannabinergico e il controllo del dolore”
From Litchman et al., 2004
Withdrawal latency (sec)
 the blockade of FAAH
doesn’t substantially
influence chronic pain
12.5
450
400
350
300
250
200
150
100
50
0
CCI
pmol/min/mg protein
“Il sistema cannabinergico e il controllo del dolore”
URB597
10.0
7.5
***
5.0
***
***
2.5
0.0
URB597
***p<0.001 vs sham (ANOVA, Tukey’s test)
“Il sistema cannabinergico e il controllo del dolore”
Withdrawal latency (sec)
 multi-targets strategy
(FAAH/AMT) seems to be
more efficacy
+++
0.0
Capsazepine
2.5
SR144528
5.0
CCI
***
SR141716
7.5
sham
VANILLOID SYSTEM?
AM404 10mg/kg
10.0
AM404
***p<0.001 vs sham (ANOVA, Tukey’s test)
“Il sistema cannabinergico e il controllo del dolore”
ANANDAMIDE AS
ENDOVANILLOID
“Il sistema cannabinergico e il controllo del dolore”
 the pivotal role of vanilloid system in inflammatory and
persistent pain suggests that the development of “hybrid”
(cannabinoid/vanilloid) compounds has promising effect
in this pathology
“Il sistema cannabinergico e il controllo del dolore”
CB1 agonists
selective for
peripheral
receptors
FAAH
inhibitors or
AMT blockers
Nonpsychoactive
cannabinoids
Selective CB2
agonists
“Il sistema cannabinergico e il controllo del dolore”
AJULEMIC ACID
“Il sistema cannabinergico e il controllo del dolore”
VR1
desensitization
CB1 and/or CB2
ENDOCANNABINOID TONE
Fatty acid amide hydrolase
Anandamide membrane
transporter
“Il sistema cannabinergico e il controllo del dolore”
“Il sistema cannabinergico e il controllo del dolore”
9
***
6
***
3
CPZ/CBD
SR1/CBD
SR2/CBD
CBD
0
SHAM
Paw withdrawal latency (sec)
12
CCI
***p<0.001 vs sham (ANOVA, Tukey’s test)
“Il sistema cannabinergico e il controllo del dolore”
“Il sistema cannabinergico e il controllo del dolore”
Non
psycho-
active cannabinoids
FAAH or AMT
inhibitors
multi
target
preparations
CB1
agonists
CB receptors
inactive
cannabinoids
CB2
agonists
Gabriella Giagnoni
Mariapia Colleoni
Anna Elisa Trovato
Francesca Comelli