ALTERATIONS IN NEUROKININ-1 RECEPTOR GENE-EXPRESSION IN MODELS OF PAIN AND INFLAMMATION

Substance P and the related tachykinin peptides are involved in inflam matory processes and in the transmission of sensory nociceptive inform ation. In this article we review the evidence implicating substance P and the neurokinin 1 (NK1) receptor in arthritic disease. We also prov ide preliminary evidence demonstrating that cultured synoviocytes from a patient with rheumatoid arthritis express NK1 receptor mRNA that ca n be downregulated by tumor necrosis factor alpha, whereas synoviocyte s from a normal patient do not express detectable NK1 receptor mRNA or protein. Data are also presented summarizing recent studies on nocice ption-induced increases in sensory ganglia of levels of mRNA encoding substance P and increases in dorsal horn NK1 receptor mRNA levels. Mor phine pretreatment blocked the increases in dorsal horn NK1 receptor m RNA levels but did not block the nociception-induced substance P encod ing mRNA levels in sensory ganglia. These results are discussed with r eference to mechanisms that may regulate substance P turnover and NK1 receptor sensitivity in models of pain and inflammation.