Alterations in neurokinin 1 receptor gene expression in models of pain and inflammation.
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 NK1 receptor mRNA that can be downregulated by tumor necrosis factor alpha, whereas synoviocytes from a normal patient do not express detectable NK1 receptor 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 NK1 receptor mRNA levels. Morphine pretreatment blocked the increases in dorsal horn NK1 receptor 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 P turnover and NK1 receptor sensitivity in models of pain and inflammation.
Krause
J E
JE
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
DiMaggio
D A
DA
McCarson
K E
KE
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D010146:Pain / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000235:genetics* / Q000502:physiology; D013373:Substance P / Q000235:genetics / Q000502:physiology
D018040:Receptors, Neurokinin-1; D013373:Substance P