Nerve-growth factor (NGF), a member of the neurotrophin family, plays an important role in nociceptor function. Prompted by a previous uinexpected finding that NT-4/5, as well as NGF sensitizes single nociceptors to noxious heat, we have explored the relative potency of all neurotrophins in eliciting thermal hyperalgesia. NGF, brain-derived neurotrophic factor (BDNF), NT-4/5 and NT-3 were injected locally into the hind paw of rats, and the behavioral response to noxious heat was compared with that from the other paw that received an identical injection of vehicle. Like NGF, agonists of tyrosine kinaseB (trkB) receptors (NT-4/5 and BDN F) induced thermal hyperalgesia in the first 5 h after treatment (NT-4/5 > BDNF) but the effect had worn off by 24 h. In contrast, the trkC agonist NT-3 had no effect on the response to noxious heat. Electrophysiological recordings from single C-fibres in the in vitro skin-saphenous nerve preparation revealed sensitization to noxious heat stimuli after direct application of BDNF to the receptive field, as previously noted for NT-4/5, and in parallel with the behavioral findings. NT-3 was ineffective as in the behavioral studies. These results suggest that trkB agonists BDNF and NT-4/5 as well as the trkA agonist NGF can regulate nociceptive responses to noxious heat.