Spinal interleukin-1beta 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-1beta (IL-1beta) is a cytokine that is an important mediator of the inflammatory response. In addition, IL-1beta 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-1beta 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-1beta produces significant antinociception when administered intrathecally in rats with peripheral inflammation (carrageenan model). The IL-1beta effect appears to be selective as it is reversed when IL-1beta is administered in the presence of an IL-1beta neutralizing antibody. We evaluated some putative mechanisms of this IL-1beta-mediated antinociception and found it to be non-opioid-dependent. Collectively, these data indicate that intrathecal IL-1beta 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-1beta is antinociceptive when applied spinally during inflammation. These results indicate that IL-1beta reduces inflammatory hyperalgesia while sparing the protective functions of acute pain. This study offers new insights into the role of IL-1beta and nociceptive processing at the level of the spinal cord and suggests that development of IL-1beta agonists may be an alternative to opiate based therapies in the treatment of inflammatory pain.
Souter
A J
AJ
Department of Anaesthesia, Royal United Hospital, Bath, UK.
Garry
M G
MG
Tanelian
D L
DL
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D007278:Injections, Spinal; D007375:Interleukin-1 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D019138:Antibodies, Blocking; D007375:Interleukin-1; D009292:Narcotic Antagonists; D009270:Naloxone; D002351:Carrageenan