Alterations in neurokinin 1 receptor gene expression in models of pain and inflammation

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Abstract
Substance P and the related tachykinin peptides are involved in inflammatory processes and in the transmission of sensory nociceptive information. In this article we review the evidence implicating substance P and the neurokinin 1 (NK1) receptor in arthritic disease. We also provide preliminary evidence demonstrating that cultured synoviocytes from a patient with rheumatoid arthritis express NK1receptor mRNA that can be downregulated by tumor necrosis factor α, whereas synoviocytes from a normal patient do not express detectable NK1receptor mRNA or protein. Data are also presented summarizing recent studies on nociception-induced increases in sensory ganglia of levels of mRNA encoding substance P and increases in dorsal horn NK1receptor mRNA levels. Morphine pretreatment blocked the increases in dorsal horn NK1receptor mRNA levels but did not block the nociception-induced substance P encoding mRNA levels in sensory ganglia. These results are discussed with reference to mechanisms that may regulate substance P turnover and NK1receptor sensitivity in models of pain and inflammation.Key words: substance P, dorsal root ganglia, G-protein-coupled receptor, Formalin test, synovium.