Disruption of the substance P receptor (neurokinin-1) gene does not prevent upregulation of preprotachykinin-A mRNA in the spinal cord of mice following peripheral inflammation.
The neuropeptide substance P is thought to play an important role in nociception, although the function of the peptide remains controversial. Following peripheral inflammation there is a pronounced upregulation of substance P expression both in sensory neurons and in postsynaptic neurons within the spinal cord. We have examined the levels of expression of mRNA encoding substance P and dynorphin following the development of inflammatory hyperalgesia in mice in which the substance P receptor gene, also known as the neurokinin-1 receptor gene, has been disrupted by homologous recombination. We show that inflammatory hyperalgesia following injection of complete Freund's adjuvant develops normally in animals that lack the neurokinin-1 receptor and that expression of mRNAs encoding substance P and the neuropeptide dynorphin are upregulated regardless of the genotype of the mouse. This suggests that substance P activity is not required for the development and maintenance of inflammatory hyperalgesia and that the upregulation of substance P expression is mediated by neurotransmitters other than substance P.
Palmer
J A
JA
Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK. j.palmer@ucl.ac.uk
De Felipe
C
C
O'Brien
J A
JA
Hunt
S P
SP
D000818:Animals; D004399:Dynorphins / Q000235:genetics; D005620:Freund's Adjuvant; D015870:Gene Expression / Q000276:immunology; D006930:Hyperalgesia / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009443:Neuritis / Q000139:chemically induced / Q000276:immunology*; D010525:Peripheral Nerves / Q000276:immunology; D020671:Posterior Horn Cells / Q000737:chemistry / Q000276:immunology*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000032:analysis / Q000235:genetics*; D013373:Substance P / Q000235:genetics; D015320:Tachykinins / Q000235:genetics*
D011498:Protein Precursors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D004399:Dynorphins; D005620:Freund's Adjuvant