Anatomical evidence supporting the potential for modulation by multiple neurotrophins in the majority of adult lumbar sensory neurons.

Neurotrophins exert effects on sensory neurons through receptor tyrosine kinases (trks) and a common neurotrophin receptor (p75). Quantitative in situ hybridization studies were performed on serial sections to identify neurons expressing single or multiple neurotrophin trk receptor mRNA(s) in adult lumbar dorsal root ganglion (DRG) in order to examine the possibility of multi-neurotrophin modulation of phenotype via different trk receptors or various trk isoforms. Expression of mRNA encoding trkA, trkB, trkC, or p75 is restricted to select subpopulations representing approximately 41%, 33%, 43%, and 79% of DRG neurons, respectively. Colocalization studies reveal that approximately 10% of DRG neurons coexpress trkA and trkB mRNA; 19% coexpress trkA and trkC mRNA; and 18% coexpress trkB and trkC mRNA. Trilocalization of all three trk mRNAs is rare, with approximately 3-4% of neurons in this category. Overall incidence of expression of more than one full length trk mRNA occurs in approximately 40% of DRG neurons, whereas expression of individual trk mRNA is found in approximately 34%. Full length trk receptor mRNA is rarely detected without p75, implicating the latter in neuronal response to neurotrophins. Examination of two full-length isoforms of trkA reveal that they are coexpressed with relative levels of expression positively correlated. TrkC mRNAs corresponding to 14- or 39-amino acid insert isoforms colocalize with the non-insert trkC isoform, but the converse is not necessarily true. The data suggest that substantial subpopulations of adult sensory neurons may be modulated through interactions with multiple neurotrophins, the consequences of which are largely unknown.