Mucosal Breaks from Periodontal Disease Likely Promotes Rheumatoid Arthritis

PainRelief.com Interview with:
Dana Orange MD
Associate Professor of Clinical Investigation
The Rockefeller Institute and
William H. Robinson, MD PhD
James W. Raitt, M.D., Professor Medicine
Immunology & Rheumatology
Stanford Health Care

PainRelief.com: What is the background for this study?

Response: Periodontitis is more common in patients with rheumatoid arthritis than those without.  

Of patients with rheumatoid arthritis, those with current periodontitis are less likely to receive benefit from treatment with biologic agents than those without periodontitis.

Repurposing Old Drugs May Lead to Chronic Pain Relief Medications

PainRelief.com Interview with:
Shane Cronin PhD
Staff scientist in the Penninger lab at IMBA
Former postdoc in the Woolf lab at Harvard Medical School and
F.M. Kirby Neurobiology Center, Boston Children’s Hospital

PainRelief.com: What is the background for this study?

Response: We and others have shown that the BH4 (tetrahydrobiopterin) metabolic pathway is upregulated in injured nerves and contributes to pain hypersensitivity in various rodent models of chronic pain. BH4 is a metabolite and an important cofactor for the aromatic amino acid hydroxylases for the production of dopamine and serotonin for example. it has also been previously shown to exert cofactor independent roles such as ROS scavenging and Fe3+ reduction in maintaining mitochondrial health.

Moreover, gene association studies in humans have also demonstrated a correlation between low levels of the bottleneck enzyme for BH4 biosynthesis, GCH1, and reduced severity of chronic pain (nicely reviewed here: PMID: 28667479). We believe that targeting this increase of BH4 after nerve injury is a viable strategy to reduce the ensuing pain. So, we set up a screening platform using transgenic mouse DRG neurons in which GFP is controlled by the Gch1 promoter – when Gch1 is turned on (as is in the case of nerve injury), GFP gets turned on as a proxy for BH4 activation and ‘in vitro cellular pain’.