Spinal interleukin-1 beta reduces inflammatory pain

Inflammation or injury often lead to chronic pain states such as hyperalges ia where the perception of a normally painful stimulus is significantly exa ggerated. Interleukin-1 beta (IL-1 beta) is a cytokine that is an important mediator of the inflammatory response. in addition, IL-1 beta has been imp licated in the modulation of pain transmission in both the peripheral and c entral nervous systems. We evaluated the spinal effect of this cytokine in the presence and absence of a peripheral carrageenan inflammation in rats s ince the spinal cord is a major region of the central nervous system in whi ch nociceptive input is processed and modulated. Our results indicate that intrathecal IL-1 beta has no effect on the latency of paw withdrawal in res ponse to a noxious thermal stimuluation in normal rats. In contrast, we hav e observed that IL-1 beta produces significant antinociception when adminis tered intrathecally in rats with peripheral inflammation (carrageenan model ). The IL-1 beta effect appears to be selective as it is reversed when IL-1 beta is administered in the presence of an IL-1 beta neutralizing antibody . We evaluated some putative mechanisms of this IL-1 beta-mediated antinoci ception and found it to be non-opioid-dependent. Collectively, these data i ndicate that intrathecal LL-1 beta has no effect on the processing of therm al nociceptive information in the absence of a peripheral inflammation. The refore, the response to acute pain remains normal in these rats. In contras t, IL-1 beta is antinociceptive when applied spinally during inflammation. These results indicate that IL-1 beta reduces inflammatory hyperalgesia whi le sparing the protective functions of acute pain. This study offers new in sights into the role of IL-1 beta and nociceptive processing at the level o f the spinal cord and suggests that development of IL-1 beta agonists may b e an alternative to opiate based therapies in the treatment of inflammatory pain. (C) 3000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.