Acute and conditioned hyperalgesic responses to illness

Pain. 1994 Feb;56(2):227-234. doi: 10.1016/0304-3959(94)90098-1.


It has been argued that pain functions to facilitate recovery from injury and/or illness by stimulating recuperative behaviors. If this is the case, then hyperalgesia might be expected to be part of the constellation of adaptations that occur during sickness. The present series of studies tested two agents that induce illness (lithium chloride and bacterial cell-wall endotoxin (lipopolysaccharide)) to determine their acute effects on pain responsivity in rats. Both agents produced hyperalgesia as measured by the tail-flick and formalin tests. This enhanced responsivity appears to be specific to pain since (a) no enhanced response was observed to a non-painful stimulus (6 g von Frey hairs), and (b) the effect could not be accounted for by changes in tail skin temperature. In addition, a conditioned taste aversion paradigm was used to examine the possibility that illness-induced hyperalgesia could be conditioned to a novel taste (saccharine). This procedure was successful in producing a conditioned hyperalgesia which was comparable in magnitude and duration to acute illness induced pain facilitation. Taken together, this series of studies suggests that such pain facilitation might have adaptive functions similar to those ascribed to other illness-induced behaviors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Avoidance Learning / physiology*
  • Disease / psychology*
  • Formaldehyde
  • Hot Temperature
  • Hyperalgesia / chemically induced
  • Hyperalgesia / psychology*
  • Injections, Intraperitoneal
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / pharmacology
  • Lithium Chloride / administration & dosage
  • Lithium Chloride / pharmacology
  • Male
  • Nociceptors / physiology*
  • Pain Measurement / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Skin Temperature / drug effects
  • Taste / drug effects


  • Lipopolysaccharides
  • Formaldehyde
  • Lithium Chloride