Spinal interleukin-1β reduces inflammatory pain

Inflammation or injury often lead to chronic pain states such as hyperalgesia where the perception of a normally painful stimulus is significantly exaggerated. 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 implicated in the modulation of pain transmission in both the peripheral and central nervous systems. We evaluated the spinal effect of this cytokine in the presence and absence of a peripheral carrageenan inflammation in rats since the spinal cord is a major region of the central nervous system in which nociceptive input is processed and modulated. Our results indicate that intrathecal IL-1 beta has no effect on the latency of paw withdrawal in response to a noxious thermal stimuluation in normal rats. In contrast, we have observed that IL-1 beta produces significant antinociception when administered 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 antinociception and found it to be non-opioid-dependent. Collectively, these data indicate that intrathecal LL-1 beta has no effect on the processing of thermal nociceptive information in the absence of a peripheral inflammation. Therefore, the response to acute pain remains normal in these rats. In contrast, IL-1 beta is antinociceptive when applied spinally during inflammation. These results indicate that IL-1 beta reduces inflammatory hyperalgesia while sparing the protective functions of acute pain. This study offers new insights into the role of IL-1 beta and nociceptive processing at the level of the spinal cord and suggests that development of IL-1 beta agonists may be 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.