Neurotrophins in spinal cord nociceptive pathways

Neurotrophins are a well-known family of growth factors for the central and peripheral nervous systems. In the course of the last years, several lines of evidence converged to indicate that some members of the family, particularly NGF and BDNF, also participate in structural and functional plasticity of nociceptive pathways within the dorsal root ganglia and spinal cord. A subpopulation of small-sized dorsal root ganglion neurons is sensitive to NGF and responds to peripheral NGF stimulation with upregulation of BDNF synthesis and increased anterograde transport to the dorsal horn. In the latter, release of BDNF appears to modulate or even mediate nociceptive sensory inputs and pain hypersensitivity. We summarize here the status of the art on the role of neurotrophins in nociceptive pathways, with special emphasis on short-term synaptic and intracellular events that are mediated by this novel class of neuromessengers in the dorsal horn. Under this perspective we review the findings obtained through an array of techniques in naïve and transgenic animals that provide insight into the modulatory mechanisms of BDNF at central synapses. We also report on the results obtained after immunocytochemistry, in situ hybridization, and monitoring intracellular calcium levels by confocal microscopy, that led to hypothesize that also NGF might have a direct central effect in pain modulation. Although it is unclear whether or not NGF may be released at dorsal horn endings of certain nociceptors in vivo, we believe that these findings offer a clue for further studies aiming to elucidate the putative central effects of NGF and other neurotrophins in nociceptive pathways.