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
Ja. Palmer et al., 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, EUR J NEURO, 11(10), 1999, pp. 3531-3538
The neuropeptide substance P is thought to play an important role in nocice
ption, although the function of the peptide remains controversial. Followin
g 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 sub
stance P and dynorphin following the development of inflammatory hyperalges
ia in mice in which the substance P receptor gene, also known as the neurok
inin-1 receptor gene, has been disrupted by homologous recombination. We sh
ow that inflammatory hyperalgesia following injection of complete Freund's
adjuvant develops normally in animal that lack the neurokinin-1 receptor an
d that expression of mRNAs encoding substance P and the neuropeptide dynorp
hin are upregulated regardless of the genotype of the mouse. This suggests
that substance P activity is not required for the development and maintenan
ce of inflammatory hyperalgesia and that the upregulation of substance P ex
pression is mediated by neurotransmitters other than substance P.