Intraspinal injection of
quisqualic acid (QUIS) produces excitotoxic injury with pathophysiological characteristics similar to those associated with ischemic and traumatic
spinal cord injury (SCI). Responses to QUIS-induced injury include an inflammatory component, as well as the development of spontaneous and evoked
pain behaviors. We hypothesized that QUIS-induced
inflammation and subsequent gene expression contribute to the development and progression of
pain-related behaviors and that blockade of
inflammation-related gene expression leads to the amelioration of these behaviors. Using the QUIS model of
spinal cord injury, we examined whether
interleukin-10 (IL-10), a potent anti-inflammatory
cytokine, is able to reduce
mRNA levels of inflammatory and cell death-related genes leading to a reduction of
pain behaviors. The results demonstrate that animals receiving systemic injection of
IL-10, 30 minutes following QUIS-induced SCI, showed a significant delay in the onset of excessive grooming behavior, a significant reduction in grooming severity, and a significant reduction in the longitudinal extent of a pattern of neuronal loss within the spinal cord characterized as "grooming-type damage." QUIS
injections also resulted in an increase in
mRNA levels of
interleukin-1 beta (IL-1 beta),
cyclooxygenase-2 (COX-2),
inducible nitric oxide synthase (iNOS),
CD95 ligand (CD95-L, also called FAS-L/APO-1L), and
tumor necrosis factor-related apoptosis-inducing
ligand (TRAIL). Results of QUIS injury plus
IL-10 treatment resulted in a significant downregulation of IL1-beta and iNOS
mRNA and these results were supported by Western blot analysis of
protein levels following
IL-10 treatment. These data suggest that
IL-10 reduces
inflammation and that targeting injury-induced
inflammation is an effective strategy for limiting the extent of neuronal damage following excitotoxic SCI and thus the onset and progression of injury-induced
pain behaviors.