Diversity of neurotrophin action in the postnatal spinal cord

The expression of neurotrophins and their receptors in the adult spinal cord indicates that they have postnatal actions in addition to their well-known prenatal ones on axonal growth and cell survival. In this review we summarize evidence in support of mechanisms by which neurotrophins acutely modulate the response both of sensory neurons and of synapses within the spinal cord. The selective action of neurotrophins is achieved via restricted expression of high affinity trk receptors through which the neurotrophins act. Activation of trk receptors enhances the response of the vanilloid VR-1 receptor in nociceptive neurons leading to peripheral sensitization of the response to capsaicin or noxious heat. At synapses on motoneurons trk receptor activation enhances the response of NMDA receptors that in turn can increase the response of AMPA/kainate receptors on the same cell. Both of these sensitizing actions have a very rapid onset that is contrasted with slower neurotrophin effects on growth of axotomized afferents. It is likely that these different functional effects of neurotrophins reflect activation of different intracellular signaling pathways. These studies suggest mechanisms by which neurotrophins might be used to improve function of the damaged spinal cord.