Simultaneous analysis of the time course for changes in core body temperature, activity, and nociception following systemic administration of interleukin-1beta in the rat.

The aches and pains that accompany fever appear to be mediated, at least in part, by the peripheral release of cytokines such as interleukin-1beta (IL-1beta). The objective of this study was to determine, whether changes in nociceptive sensitivity produced by IL-1beta administration are temporally linked to changes in core body temperature. Experiment 1 examined nociceptive responsiveness for a period of 3 h following systemic administration of IL-1beta (1, 3, 10 and 20 microg/kg). The two highest doses of IL-1beta produced a drop in temperature beginning approximately 60 min after cytokine administration. This hypothermia lasted 90 min and was associated with hyperalgesia. Experiment 2 examined changes in temperature and nociception for 12 h following administration of IL-1beta (10 microg/kg). An early, short-lived hypothermia was followed by a significant hyperthermia from 3.25 to 6.5 h following IL-1beta administration. This late-occurring fever was accompanied by hyperalgesia. Both the hypo- and hyperthermia phases were associated with a reduction in locomotor activity. Given that repeated nociceptive testing may confound assessment of temperature and activity, Experiment 3 examined the effects of IL-1beta (10 microg/kg) administration on temperature and activity in rats that remained in their home cages. The biphasic change in temperature and the reduction in activity were nearly identical to that reported in Experiment 2, indicating that repeated nociceptive testing did not confound these data. The results of this study demonstrate that, two phases of hyperalgesia occur and coincide with the periods of altered thermoregulation produced by systemic administration of IL-1beta.