Therapeutic efficacy in experimental polyarthritis of viral-driven enkephalin overproduction in sensory neurons

Rheumatoid arthritis is characterized by erosive inflammation of the joints , new bone proliferation, and ankylosis, leading to severely reduced locomo tion and intense chronic pain. In a model of this disease, adjuvant-induced polyarthritis in the rat, neurons involved in pain transmission and contro l undergo plastic changes, especially at the spinal level. These changes af fect notably neurons that contain opioids, such as enkephalins deriving fro m preproenkephalin A (PA) precursor protein. Using recombinant herpes simpl ex virus containing rat PA cDNA, we enhanced enkephalin synthesis in sensor y neurons of polyarthritic rats. This treatment markedly improved locomotio n and reduced hyperalgesia. Furthermore, the progression of bone destructio n slowed down, which is the most difficult target to reach in the treatment of patients suffering from arthritis. These data demonstrate the therapeut ic efficacy of enkephalin overproduction in a model of systemic inflammator y and painful chronic disorder.