Interleukin-1 receptor antagonist ameliorates neonatal lipopolysaccharide-induced long-lasting hyperalgesia in the adult rats

Toxicology. 2011 Jan 11;279(1-3):123-9. doi: 10.1016/j.tox.2010.10.002. Epub 2010 Oct 19.


An increasing amount of data show that central inflammation contributes to many debilitating diseases and produces spontaneous pain and hyperalgesia (an increased sensitivity to painful stimuli), and these processes may be associated with the production of proinflammatory cytokines by activated microglia. In the present study, we demonstrate that neonatal intracerebral injection of lipopolysaccharide (LPS) (1mg/kg) in postnatal day 5 (P5) rats produced hyperalgesia that lasted into adulthood as indicated by decreased latency in the tail-flick test. Neonatal LPS administration resulted in a long-lasting increase in the number of activated microglial in the P70 rat brain. The effects of interleukin-1beta (IL-1β) and IL-1 receptor antagonists on hyperalgesia were determined to examine the possible role of inflammatory cytokines in LPS-induced hyperalgesia. Our data show that neonatal intracerebral injection of IL-1β (1 μg/kg) produced a hyperalgesic tendency similar to that induced by LPS. Neonatal administration of an IL-1 receptor antagonist (0.1mg/kg) significantly attenuated long-lasting hyperalgesia induced by LPS and reduced the number of activated microglia in the adult rat brain. These data reveal that neonatal intracerebral LPS exposure results in long-lasting hyperalgesia and an elevated number of activated microglia in later life. This effect is similar to that induced by IL-1β and can be prevented by an IL-1 receptor antagonist. The present study suggests that an IL-1 receptor antagonist effectively attenuates or blocks long-lasting hyperalgesia and microglia activation produced by LPS exposure in the neonatal period of rats.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Disease Models, Animal
  • Hyperalgesia / physiopathology
  • Hyperalgesia / prevention & control*
  • Inflammation / physiopathology
  • Injections
  • Interleukin-1beta / administration & dosage
  • Interleukin-1beta / metabolism*
  • Lipopolysaccharides / toxicity*
  • Male
  • Microglia / drug effects*
  • Microglia / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Receptors, Interleukin-1 / metabolism
  • Time Factors


  • Interleukin-1beta
  • Lipopolysaccharides
  • Receptors, Interleukin-1