Recently, the gene Phox2a has been shown to be necessary for the development of spinal cord nerve cells which conduct pain from the body to the brain where it can be consciously perceived. We can then examine how these pain transmission circuits develop by studying Phox2a-expressing cells. During development, some cells emit chemicals (like netrin or reelin) to draw or repel other cells resulting in the proper formation of organs such as the spinal cord. This study aimed to examine the effects of two major cell migration signals implicated in persistent pain (neutrin and reelin) on the development of pain transmission circuits.<\/p>\n\n\n\n
Transgenic mice that are genetically modified to express Phox2a-expressing neurons fluorescently labeled were crossed with mice carrying altered mutant forms of the Netrin1 gene, the Dcc and Unc5c genes (involved in netrin1 signaling) and the Dab1 gene (involved in reelin signaling). Pain transmission neuron development was analyzed by visualizing the fluorescent label in mouse embryonic spinal cord under microscope.<\/p>\n\n\n\n
In mice with a mutated Netrin1 gene, pain transmission neurons which receive sensory nerve messages directly and which are associated with location of painful stimuli (located in the lamina 1 of the spinal cord) did not migrate into position, mainly due to impaired ingrowth of sensory nerve fibers into the spinal cord. In mice with a mutated Dab1 gene, pain transmission neurons which lie deep in the spinal cord and which are associated with the unpleasantness of pain (located in the lamina 5 of the spinal cord) did not migrate into position, which did not apparently depend on any other factor, suggesting that they may use reelin signaling directly.<\/p>\n\n\n\n
Brian Roome<\/a>, Artur Kania<\/a> and colleagues have shown that neutrin1 and reelin signaling genes, whose variants have previously associated with persistent pain and variations in the way pain is experienced (pain sensitivity), have pronounced effects on the development of pain transmission neurons in mice which may underlie their link to pain physiology.<\/p>\n\n\n\n