We recently reported a model in which to study the effects of immune challenge on nociceptive processing in the anaesthetised rat (Bleasdale et al. 2001). Using this model, we have now compared effects on withdrawal responses to a noxious pinch stimulus (to co-activate Aδ- and C-nociceptors) with those on withdrawal to slow rates of skin heating (to preferentially activate C-nociceptors; Yeomans & Proudfit, 1996).

Five alphaxolone/alphadalone-anaesthetised (Saffan, 14Ð24 mg kg^-1 h^-1; I.V.) rats (275Ð300 g) were instrumented to record arterial blood pressure and rectal temperature. 1.2-2.0 N pinch (15 s) of the toes, and ‘slow’ (2.5 °C s^-1) ramps (30Ð55 °C) of contact heat of the dorsal surface of the same hindpaw were alternated once every 5 min throughout the experiment (up to 8 h) and EMG was recorded from the biceps femoris to monitor thresholds and magnitudes (modulus) of withdrawal responses. Once baseline responses were established, lipopolysaccharide (LPS) was injected (0.2 mg kg^-1; I.P.) to evoke an immune response and the time course of fever monitored by noting changes in core temperature every 5 min. Animals were killed with an overdose of anaesthetic (pentobarbitone, I.V.) at the end of each experiment. All values are expressed as means ± S.E.M. and an unpaired t test was used to test levels of significance.

Following a delay of 20Ð160 min, injection of LPS induced increases in core temperature that persisted for 95Ð240 min. Peak temperatures (38.0 ± 0.04 °C) were significantly increased (unpaired t test, P < 0.0001) from control (37.5 ± 0.04 °C). During 30 min at the peak of the fever, magnitude of EMG responses to pinch stimuli of constant forces increased significantly (unpaired t test, P < 0.001) by 34.5 ± 9.68 % compared with control values taken before injection of LPS. During the same 30 min period, threshold temperatures that evoked withdrawal in response to the ramped heat stimuli were lowered significantly to 49.7 ± 0.32 °C (unpaired t test, P < 0.005) compared with control values of 52.7 ± 0.35 °C.

This study has demonstrated hyperalgesia to heat and to mechanical noxious stimuli in response to an immune challenge. As such, these data indicate that facilitatory effects on C-nociceptor-evoked activity may constitute part of a sickness response. Any effects on Aδ-nociceptor-evoked responses remain unclear and are the subject of ongoing experiments in this laboratory.

D.A.A.S. is a BBSRC Scholar. We thank Simon Lishman and Dave Gee for expert technical assistance.

All procedures accord with UK legislation.