Peripheral cannabinoid receptors exert a powerful inhibitory control over pain initiation, but the endocannabinoid signal that normally engages this intrinsic analgesic mechanism is unknown. To address this question, we developed a peripherally restricted inhibitor (URB937) of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of the endocannabinoid anandamide. URB937 suppressed FAAH activity and increased anandamide levels outside the rodent CNS. Despite its inability to access brain and spinal cord, URB937 attenuated behavioral responses indicative of persistent pain in rodent models of peripheral nerve injury and inflammation and prevented noxious stimulus-evoked neuronal activation in spinal cord regions implicated in nociceptive processing. CB₁ cannabinoid receptor blockade prevented these effects. These results suggest that anandamide-mediated signaling at peripheral CB₁ receptors controls the access of pain-related inputs to the CNS. Brain-impenetrant FAAH inhibitors, which strengthen this gating mechanism, might offer a new approach to pain therapy.

 

Nota:

Davide Piomelli  e'  il direttore  del dipartimento dell'Istituto Italiano di Tecnologia di Genova  dedicato alla  ricerca e  sviluppo  di nuovi farmaci  ed  e' anche responsabile  di un laboratorio di ricerca farmacologica all'Universita'  di Irvine in California

Questo antidolorifico in via di sperimentazioen e' molto interessante, in quanto non agisce a livello del cervello ma in periferia : in pratica  agisce impedendo la demolizione  fisiologica  di un analgesico endogeno ,  l'anandamide , il quale spegne  il dolore legandosi al recettore endocannabinoide di tipo  1  (CB1), lo stesso cui si lega la marijuana