Publications

Dernière publication 01/05/2015

A multi-target approach for pain treatment- dual inhibition of fatty acid amide

The pharmacological inhibition of anandamide (AEA) hydrolysis by fatty acid amide hydrolase (FAAH) attenuates pain in animal models of...

Array
(
    [id_prestablog_news] => 725
    [id_shop] => 1
    [date] => 2015-05-01 00:00:00
    [date_modification] => 2024-02-09 14:15:12
    [langues] => ["1","2"]
    [actif] => 1
    [slide] => 0
    [url_redirect] => 
    [average_rating] => 
    [number_rating] => 
    [author_id] => 1
    [featured] => 0
    [prim_key] => 1418
    [id_lang] => 2
    [title] => A multi-target approach for pain treatment- dual inhibition of fatty acid amide 
    [paragraph] => A multi-target approach for pain treatment: dual inhibition of fatty acid amide hydrolase and TRPV1 in a rat model of osteoarthritis
    [content] => 
Authors
Malek N, Mrugala M, Makuch W, Kolosowska N, Przewlocka B, Binkowski M, Czaja M, Morera E, Di Marzo V, Starowicz K.

 Lab
Laboratory of Pain Pathophysiology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
Journal
Pain
Abstract
The pharmacological inhibition of anandamide (AEA) hydrolysis by fatty acid amide hydrolase (FAAH) attenuates pain in animal models of osteoarthritis (OA) but has failed in clinical trials. This may have occurred because AEA also activates transient receptor potential vanilloid type 1 (TRPV1), which contributes to pain development. Therefore, we investigated the effectiveness of the dual FAAH-TRPV1 blocker OMDM-198 in an MIA-model of osteoarthritic pain. We first investigated the MIA-induced model of OA by (1) characterizing the pain phenotype and degenerative changes within the joint using X-ray microtomography and (2) evaluating nerve injury and inflammation marker (ATF-3 and IL-6) expression in the lumbar dorsal root ganglia of osteoarthritic rats and differences in gene and protein expression of the cannabinoid CB1 receptors FAAH and TRPV1. Furthermore, we compared OMDM-198 with compounds acting exclusively on FAAH or TRPV1. Osteoarthritis was accompanied by the fragmentation of bone microstructure and destroyed cartilage. An increase of the mRNA levels of ATF3 and IL-6 and an upregulation of AEA receptors and FAAH in the dorsal root ganglia were observed. OMDM-198 showed antihyperalgesic effects in the OA model, which were comparable with those of a selective TRPV1 antagonist, SB-366,791, and a selective FAAH inhibitor, URB-597. The effect of OMDM-198 was attenuated by the CB1 receptor antagonist, AM-251, and by the nonpungent TRPV1 agonist, olvanil, suggesting its action as an indirect CB1 agonist and TRPV1 antagonist. These results suggest an innovative strategy for the treatment of OA, which may yield more satisfactory results than those obtained so far with selective FAAH inhibitors in human OA.
BIOSEB Instruments Used
Dynamic Weight Bearing 2.0 (BIO-DWB-DUAL)
    [meta_description] => 
    [meta_keywords] => http://www.ncbi.nlm.nih.gov/pubmed/25719612
    [meta_title] => 
    [link_rewrite] => a-multi-target-approach-for-pain-treatment--dual-inhibition-of-fatty-acid-amide-hydrolase-and-trpv1-in-a-rat-model-of-osteoarthritis
    [actif_langue] => 1
    [read] => 1010
    [count_comments] => 0
    [id] => 725
    [categories] => Array
        (
            [70] => Array
                (
                    [id_prestablog_categorie] => 70
                    [title] => Arthrite & Arthrose
                    [link_rewrite] => Arthrite-Arthrose
                )

            [21] => Array
                (
                    [id_prestablog_categorie] => 21
                    [title] => Articulations
                    [link_rewrite] => Articulations
                )

            [2] => Array
                (
                    [id_prestablog_categorie] => 2
                    [title] => Publications
                    [link_rewrite] => publications
                )

        )

    [authors] => 
    [paragraph_crop] => A multi-target approach for pain treatment: dual inhibition of fatty acid amide hydrolase and [...]
    [link_for_unique] => 1
    [products_liaison] => Array
        (
            [1216] => Array
                (
                    [name] => Distribution Pondérale Dynamique 2.0
                    [description_short] => 
Un système permettant l'analyse de la posture des animaux par la répartition du poids sur chacune des 4 pattes. Le DWB est un test unique dans l'étude de nombreux modèles de douleurs, principalement non évoquée , neuropathique ou encore inflammatoire ainsi que pour les études sur l'osthéoarthrite et divers affections du SNC. 

Le nouvelle version DWB2 intègre une nouvelle interface logiciel plus simple avec gestion des listes d'animaux ainsi que de nouveaux algorithmes d'analyse automatique de la posture.

                    [thumb] => 
                    [img_empty] => /var/www/vhosts/de3310.ispfr.net/preprod.bioseb.com/modules/prestablog/views/img/product_link_white.jpg
                    [image_presente] => 1
                    [link] => https://preprod.bioseb.com/fr/douleur-spontanee-deficit-de-posture/1216-dynamic-weight-bearing-20.html
                )

            [1877] => Array
                (
                    [name] => Dynamic Weight Bearing 2.0 – Module Postural Additionnel
                    [description_short] => 
Étendez votre analyse grâce à des calculs posturaux et locomoteurs avancés
Le système de Distribution Pondérale Dynamique (DWB2)  de BIOSEB s’enrichit avec l'ajout du Module Postural. Ce complément logiciel optionnel améliore l’analyse standard de la répartition du poids en intégrant des nouveaux calculs conçus pour l’étude de la posture, de la locomotion et de l’activité des animaux.
Développé en collaboration avec le laboratoire du Dr. Tighilet de l’Université Aix-Marseille - CNRS, le Module Postural améliore votre DWB2 en fournissant des paramètres précieux pour les recherches sur la douleur, les troubles vestibulaires et les maladies neurodégénératives.

                    [thumb] => 
                    [img_empty] => /var/www/vhosts/de3310.ispfr.net/preprod.bioseb.com/modules/prestablog/views/img/product_link_white.jpg
                    [image_presente] => 1
                    [link] => https://preprod.bioseb.com/fr/douleur-spontanee-deficit-de-posture/1877-dynamic-weight-bearing-20-module-postural-additionnel.html
                )

        )

)
1