Treating alcohol use disorder in U.S. veterans: The role of traumatic brain injury

Objective: The authors examined the efficacy of valproate to reduce relapse to heavy drinking among veterans with alcohol use disorder (AUD) and neuropsychiatric comorbidities and whether antecedent traumatic brain injury (TBI) or posttraumatic stress disorder (PTSD) affected treatment response. Methods: Participants were male veterans 18–60 years old with an AUD and no other substance use besides nicotine or cannabis. Sixty-two patients were randomly assigned to receive either valproate or naltrexone. Participants were evaluated at baseline and followed weekly for 24 weeks. All participants received standardized psychosocial interventions as well as treatment for coexistent psychiatric conditions. Results: During the follow-up period, nine study subjects in the naltrexone group and 14 in the valproate group relapsed to heavy drinking, but the difference did not reach statistical significance. Participants with a history of moderate to severe TBI were more likely to relapse to heavy drinking compared with those with no TBI (hazard ratio=4.834, 95% CI=1.103–21.194, p=0.033). PTSD status did not significantly affect outcome. Conclusions: Intensive outpatient programs are efficacious alternatives to treat AUD in veterans, although the role of pharmacological treatment is not completely elucidated. Glutamatergic agents appear to be less effective than opiate antagonists to prevent relapse to heavy drinking and to increase cumulative abstinence. Future studies should examine novel pharmacological and nonpharmacological options.Fil: Jorge, Ricardo E.. Baylor College of Medicine;Fil: Li, Ruosha. Baylor College of Medicine;Fil: Liu, Xiangyu. Baylor College of Medicine;Fil: McGavin, Jill K.. Baylor College of Medicine;Fil: Shorter, Daryl I.. Baylor College of Medicine;Fil: Acion, Laura. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Calculo. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Calculo; ArgentinaFil: Arndt, Stephan. University of Iowa; Estados Unido

Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology

Objective Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. Methods OA was induced in wild-type (WT) and PAR2-deficient (PAR2−/−) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2−/− mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Results Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2−/− mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2−/− mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2−/− mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. Conclusions This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes