Comparative analysis of molecular signatures suggests the use of gabapentin for the management of endometriosis-associated pain - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Pain Research Année : 2018

Comparative analysis of molecular signatures suggests the use of gabapentin for the management of endometriosis-associated pain

Résumé

Background: It has been repetitively shown that the transcription factors DLX5 and DLX6 are drastically downregulated in endometriotic lesions when compared with eutopic endometrium. These findings suggest that regulatory cascades involving DLX5/6 might be at the origin of endometriosis symptoms such as chronic pelvic pain (CPP). We have shown that inactivation of Dlx5 and Dlx5/6 in the mouse uterus results in an endometrial phenotype reminiscent of endometriosis. Methods: We focused on genes that present a similar deregulation in endometriosis and in Dlx5/6-null mice in search of new endometriosis targets. Results: We confirmed a strong reduction of DLX5 expression in endometriosis implants. We identified a signature of 30 genes similarly deregulated in human endometriosis implants and in Dlx5/6-null mouse uteri, reinforcing the notion that the downregulation of Dlx5/6 is an early event in the progress of endometriosis. CACNA2D3, a component of the α2δ family of voltage-dependent calcium channel complex, was strongly overexpressed both in mutant mouse uteri and in endometriosis implants, were also CACNA2D1 and CACNA2D2, other members of the α2δ family involved in nociception, are upregulated. Conclusion: Comparative analysis of gene expression signatures from endometriosis and mouse models showed that calcium channel subunits α2δ involved in nociception can be targets for the treatment of endometriosis-associated pain. CACNA2D3 has been associated with pain sensitization and heat nociception in animal models. In patients, CACNA2D3 variants were associated with reduced sensitivity to acute noxious stimuli. As α2δs were targets of gabapentinoid analgesics, the results suggested the use of these drugs for the treatment of endometriosis-associated pain. Indeed, recent small-scale clinical studies have shown that gabapentin could be effective in women with CPP. The findings of this study reinforce the need for a large definitive trial
Fichier principal
Vignette du fichier
JPR-163611-comparative-analysis-of-molecular-signatures-suggests-the-us_-040918.pdf (5.48 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

hal-02135634 , version 1 (18-04-2024)

Identifiants

Citer

Brice Bellessort, Anne Bachelot, Virginie Grouthier, Camille de Lombares, Nicolas Narboux-Nême, et al.. Comparative analysis of molecular signatures suggests the use of gabapentin for the management of endometriosis-associated pain. Journal of Pain Research, 2018, 11 (19), pp.715-725. ⟨10.2147/JPR.S163611⟩. ⟨hal-02135634⟩
45 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More