Ectopic expression of nerve growth factor in smooth muscle cells induces sprouting of sympathetic and sensory (nociceptive) axons in the descending colon and urinary bladder – influence of the p75 neurotrophin receptor

Nerve growth factor (NGF) stimulates the directional growth of sympathetic and sensory axons during normal development. To assess how increased levels of target‐derived NGF influence the densities of these axons innervating peripheral tissues, we generated transgenic mice that ectopically express NGF under the control of the smooth muscle alpha actin promoter. Since we have previously shown that an absence of functional p75 neurotrophin receptor (p75NTR) on sympathetic and sensory axons can affect NGF‐mediate sprouting, we generated NGF transgenic lacking p75NTR expression (i.e., NGF/p75−/− mice). Adult NGF/p75−/− mice displayed comparable densities of sympathetic axons in the muscular externa of the descending colon and in the urinary bladder with age‐matched NGF/p75+/+ siblings. Unexpectedly, adult NGF/p75−/− mice displayed a marked depletion of sensory (i.e., specifically nociceptive) axons in the muscular externa of the descending colon, as compared to age‐matched NGF/p75+/+ siblings; densities of sensory axons were, however, comparable between NGF/p75−/− and NGF/p75+/+ mice. These data reveal the selective importance of p75NTR expression for NGF‐mediated sprouting by sympathetic and sensory axons, which may signal different responses of these fibers to colonic or bladder inflammation. This work was support by the Canadian Institutes of Health Research (CIHR). Grant Funding Source : CIHR