Effects of interleukin-10 (IL-10) on pain behavior and gene expression following excitotoxic spinal cord injury in the rat

Intraspinal injection of quisqualic acid (QUIS) produces excitotoxic injury with pathophysiological characteristics similar to those associated with i schemic and traumatic spinal cord injury (SCI), Responses to QUIS-induced i njury include an inflammatory component, as well as the development of spon taneous and evoked pain behaviors. We hypothesized that QUIS-induced inflam mation and subsequent gene expression contribute to the development and pro gression of pain-related behaviors and that blockade of inflammation-relate d gene expression leads to the amelioration of these behaviors. Using the Q UIS model of spinal cord injury, we examined whether interleukin-10 (IL-10) , a potent anti inflammatory cytokine, is able to reduce mRNA levels of inf lammatory and cell death-related genes leading to a reduction of pain behav iors. 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 groom ing severity, and a significant reduction in the longitudinal extent of a p attern of neuronal loss within the spinal cord characterized as "grooming-t ype damage." QUIS injections also resulted in an increase in mRNA levels of interleukin-l 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 o f 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 t hat IL-10 reduces inflammation and that targeting injury-induced inflammati on is an effective strategy for limiting the extent of neuronal damage foll owing excitotoxic SCI and thus the onset and progression of injury-induced pain behaviors. (C) 2001 Academic Press.