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The Journal of Neuroscience, July 15, 2001, 21(14):5321-5327
PKC Contributes to a Subset of the NMDA-Dependent Spinal
Circuits That Underlie Injury-Induced Persistent Pain
William J.
Martin,
Annika B.
Malmberg, and
Allan I.
Basbaum
Departments of Anatomy and Physiology and W. M. Keck
Foundation Center for Integrative Neuroscience, University of
California, San Francisco, San Francisco, California 94143-0452
In previous studies we provided evidence that the  isoform of protein kinase C (PKC) is an important contributor to the increased pain sensitivity that occurs after injury. Here we combined electrophysiological and behavioral approaches in wild-type and PKC-null mice to compare the hyperexcitability of wide dynamic range
neurons in lamina V of the spinal cord dorsal horn with the behavioral
hyperexcitability produced by the same injury [application of a
C-fiber irritant, mustard oil (MO), to the hindpaw]. Wild-type and
null mice did not differ in their response to mechanical or thermal
stimuli before tissue injury, and the magnitude of the response to the
MO stimuli was comparable. In wild-type mice, MO produced a dramatic
and progressive enhancement of the response of lamina V neurons to
innocuous mechanical and thermal stimuli. The time course of the
neuronal hyperexcitability paralleled the time course of the MO-induced
behavioral allodynia (nocifensive behavior in response to a previously
innocuous mechanical stimulus). Neuronal hyperexcitability was also
manifest in the PKC-null mice, but it lasted <30 min. By contrast,
the behavioral allodynia produced by MO in the PKC-null mice,
although reduced to approximately half that of the wild-type mice,
persisted long after the lamina V hyperexcitability had subsided.
Because the MO-induced behavioral allodynia was completely blocked by
an NMDA receptor antagonist, we conclude that PKC mediates the
transition from short- to long-term hyperexcitability of lamina V
nociresponsive neurons but that the persistence of injury-induced pain
must involve activity within multiple NMDA-dependent spinal cord circuits.
Key words:
mustard oil; protein kinase C; NMDA; isoform; persistent pain; spinal cord
Copyright © 2001 Society for Neuroscience 0270-6474/01/21145321-07$05.00/0
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