Is ATP the missing link between peripheral nerve injury and the enhanced regenerative capacity of sensory neurons? (360G-Wellcome-084688_Z_08_Z)

The basic aim is to understand the events in injured peripheral nerves which lead to retrograde activation of events in neurons which are beneficial to axonal regeneration. We will test the specific hypothesis, supported by preliminary data, that ATP released instantly upon nerve injury triggers the subsequent release of the cytokines. Specific aims are 1) to determine whether P2 receptor antagonists can attenuate the enhanced axon regeneration by peripheral nerve injury or intraneurally injecte d ATP, 2) to determine whether intraneural injection of ATP can stimulate cell body responses favourable to regeneration in vivo, 3) to see whether or not axonal regeneration is impaired in mice with knockout of the P2X7 receptor, 4) to identify the early signal pathways activated in DRG neurons by intraneurally injected ATP, 5) to assess the effects of media conditioned by non-neuronal cells in peripheral nerves on neurite outgrowth from neurons in vitro and 6) to seek evidence that ATP stimula tes the release of candidate cytokines from non-neuronal cells in nerves.