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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

Authors

  • James A. Palmer,

    Corresponding author
    1. Neurobiology Division, MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK
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    • *Present address: Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, 46 Cleveland Street, London, W1P 6DB, UK

      Present address: Department of Anatomy and Developmental Biology, Medawar Building, University College London, Gower Street, London, WC1E 6BT, UK

  • Carmen De Felipe,

    1. Instituto de Neurociencias, Universidad Miguel Hernández, Campus San Juan, Ctra. Alicante-Valencia, Km. 87-E-03550 San Juan, Alicante, Spain
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  • John A. O'Brien,

    1. Neurobiology Division, MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK
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  • Stephen P. Hunt

    1. Neurobiology Division, MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK
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    • *Present address: Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, 46 Cleveland Street, London, W1P 6DB, UK

      Present address: Department of Anatomy and Developmental Biology, Medawar Building, University College London, Gower Street, London, WC1E 6BT, UK


Abstract

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.

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