Therapeutic Efficacy in Experimental Polyarthritis of Recombinant Virus-Driven Enkephalin Overproduction in Sensory Neurons

摘要

Rheumatoid arthritis is a systemic autoimmune disease primarily manifested by erosive inflammation of the joints associated with intense pain (Harris 1990). Its etiology is still unknown, but significant insights into its physiopathology have been obtained from experimental animal models. Although none of these models has all the characteristics of the human disease, adjuvant-induced polyarthritis in the rat shares numerous behavioral and biochemical characteristics with rheumatoid arthritis (Calvino et al. 1987). Profound neurochemical changes in the peripheral and central nervous systems are associated with long-term alterations of pain processing and hyper-algesia in these animals (Millan et al. 1987). Thus, in polyarthritic rats, both preproenkephalin A (PA) expression and the levels of PA-derived peptides are enhanced in the dorsal horn of the spinal cord, particularly in the lumbar region that receives sensory nerves from the hindpaws (which are especially affected by the disease) (Cesselin et al. 1980). By contrast, PA expression drops in cell bodies of primary sensory neurons located in lumbar dorsal root ganglia (DRG), and the concentration of the main PA-derived peptide, met-enkephalin, is reduced in the soft tissue of ankle joints in polyarthritic rats (Pohl et al. 1994; El Hassan et al. 1998).