Wj. Martin et al., PKC gamma contributes to a subset of the NMDA-dependent spinal circuits that underlie injury-induced persistent pain, J NEUROSC, 21(14), 2001, pp. 5321-5327
In previous studies we provided evidence that the gamma isoform of protein
kinase C (PKC gamma) is an important contributor to the increased pain sens
itivity that occurs after injury. Here we combined electrophysiological and
behavioral approaches in wild-type and PKC gamma -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 hindpa
w]. 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 innocuo
us mechanical and thermal stimuli. The time course of the neuronal hyperexc
itability paralleled the time course of the MO-induced behavioral allodynia
(nocifensive behavior in response to a previously innocuous mechanical sti
mulus). Neuronal hyperexcitability was also manifest in the PKC gamma -null
mice, but it lasted <30 min. By contrast, the behavioral allodynia produce
d by MO in the PKC<gamma>-null mice, although reduced to approximately half
that of the wild-type mice, persisted long after the lamina V hyperexcitab
ility had subsided. Because the MO-induced behavioral allodynia was complet
ely blocked by an NMDA receptor antagonist, we conclude that PKC gamma medi
ates 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.