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Nature 392, 390-394 (26 March 1998) | doi:10.1038/32897; Received 1 December 1997; Accepted 17 February 1998

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Primary afferent tachykinins are required to experience moderate to intense pain

Yu Qing Cao1, Patrick W. Mantyh2, Elaine J. Carlson3, Anne-Marie Gillespie3, Charles J. Epstein3 & Allan I. Basbaum1

  1. Departments of Anatomy, Physiology and W. M. Keck Foundation Center for Integrative Neuroscience,
  2. Molecular Neurobiology Laboratory, Veterans Administration Medical Center and Department of Psychiatry, University of Minnesota, Minneapolis, Minneapolis 55417, USA
  3. Department of Pediatrics, University of California San Francisco, UCSF Box 0452, San Francisco, California 94143-0452, USA

Correspondence to: Allan I. Basbaum1 Correspondence and requests for materials should be addressed to A.I.B. (e-mail: Email: aib@phy.ucsf.edu).

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The excitatory neurotransmitter glutamate coexists with the peptide known as substance P in primary afferents that respond to painful stimulation1. Because blockers of glutamate receptors reliably reduce pain behaviour2, 3, 4, it is assumed that 'pain' messages are mediated by glutamate action on dorsal horn neurons. The contribution of substance P, however, is still unclear. We have now disrupted the mouse preprotachykinin A gene (PPT-A), which encodes substance P and a related tachykinin, neurokinin A (ref. 5). We find that although the behavioural response to mildly painful stimuli is intact in these mice, the response to moderate to intense pain is significantly reduced. Neurogenic inflammation, which results from peripheral release of substance P and neurokinin A (ref. 6), is almost absent in the mutant mice. We conclude that the release of tachykinins from primary afferent pain-sensing receptors (nociceptors) is required to produce moderate to intense pain.

  1. Departments of Anatomy, Physiology and W. M. Keck Foundation Center for Integrative Neuroscience,
  2. Molecular Neurobiology Laboratory, Veterans Administration Medical Center and Department of Psychiatry, University of Minnesota, Minneapolis, Minneapolis 55417, USA
  3. Department of Pediatrics, University of California San Francisco, UCSF Box 0452, San Francisco, California 94143-0452, USA

Correspondence to: Allan I. Basbaum1 Correspondence and requests for materials should be addressed to A.I.B. (e-mail: Email: aib@phy.ucsf.edu).