CORNEAL INNERVATION AND SENSITIVITY TO NOXIOUS STIMULI IN TRKA KNOCKOUT MICE

Most primary sensory neurones depend on neurotrophins for survival. Mu tant mice in which TrkA, the high-affinity receptor for nerve growth f actor (NGF), has been inactivated lack nociceptive neurones in sensory ganglia and do not respond to noxious stimuli, The cornea of the eye is innervated by trigeminal neurones that are activated by noxious mec hanical, thermal and chemical stimuli. In the human cornea, these stim uli evoke only sensations of pain. We have analysed the innervation pa ttern and the response to noxious stimulation of the cornea of trkA (- /-) mutant mice. Corneal nerves were stained with the gold chloride im pregnation method, Corneal sensitivity to noxious stimuli was assessed by counting blinking movements evoked by von Frey hairs, topical appl ication of saline at different temperatures and application of acetic acid and capsaicin at different concentrations. In the cornea of trkA (-/-) mutant animals, we observed a drastic reduction in the number of nerve trunks and branches in the corneal stroma. Furthermore, quantit ative analysis of the number of thin nerve terminals revealed a marked decrease in the corneal epithelium of trkA (-/-) mice when compared t o those present in wild type and trkA (+/-) animals. The blinking resp onse of trkA (-/-) mice to mechanical, thermal and chemical noxious st imuli was also significantly reduced. These results indicate that the population of corneal sensory neurones is markedly depleted in trkA (- /-) mutant mice. However, a small portion of corneal sensory neurones survive in these mice suggesting that they may be NGF independent. On the basis of our results, we propose that these surviving cells are po lymodal nociceptive neurones, sensitive to mechanical stimulation, nox ious heat and acid.