PGE2-induced lasting nociception to heat: Evidences for a selective involvement of A-delta fibres in the hyperpathic component of hyperalgesia

Animal models for mechanical pressure or heat nociception usually only measure the threshold response latency. In this study, the effect of typical sensitising treatments on the lasting nocifensive behaviour elicited after a supra-threshold heating stimulus – the hyperpathic component of hypernociception – was assessed. Male Wistar rats received either intra-plantar (i.pl.) injection of 350ng PGE2 (50μL) or topical application (t.a.) of 100% dimethylsulfoxide (DMSO), and 10mM capsaicin. One hour after the paw treatments the number of nocifensive events (NNE) was scored hourly (6h), for 5min, immediately after a hind paw immersion in hot water (50°C/7s). PGE2, DMSO and capsaicin increased the NNE -induced by the supra-threshold stimuli. Indomethacin (2.5mg/kg i.p.), given 30min before paw treatments, completely inhibited NNE in all groups (P<0.01). However, indomethacin given 60min after PGE2 did not reverse this sensitisation. PGE2 and DMSO did not lower the heat threshold in the paw withdrawal test, although carrageenan and capsaicin were effective (P<0.05). Capsaicin neonatal treatment (CNT) (50mg/kg) reduced the sensitisation induced by DMSO and capsaicin (P<0.01), but not that induced by PGE2. These data suggest that the heat-induced lasting nociception is probably conveyed by Að nociceptors, and PGE2 seems to be more selective to induce this phenomenon than the thermal threshold lowering. In addition, this hyperpathic effect induced by DMSO and capsaicin seems to be indirectly mediated by PGE2 and C-fibres.