PRESENCE OR ABSENCE OF TRKA PROTEIN DISTINGUISHES SUBSETS OF SMALL SENSORY NEURONS WITH UNIQUE CYTOCHEMICAL CHARACTERISTICS AND DORSAL HORNPROJECTIONS

Investigations into the biological actions of nerve growth factor (NGF ) have shown that dorsal root ganglion (DRG) neurons subserving nocice ption require NGF for survival and maintenance of phenotype. This disc overy suggests that the signaling NGF receptor, TrkA, can be used as a marker for nociceptive neurons. In this study, we have used antibodie s to TrkA, in conjunction with cell biological markers that show a res tricted distribution in the DRG, to further characterize subsets of DR G neurons that are dependent upon NGF. Staining for TrkA labeled small and medium-sized neurons that composed 47% of all neurons in thoracic ganglia. Double-labeling with antibodies to the high molecular weight neurofilament protein (NFH), a marker for neurons with myelinated axo ns, demonstrated that TrkA staining is found in only a small subset of myelinated neurons. Surprisingly, many DRG neurons were not labeled b y either TrkA or NFH. These neurons had small soma areas, contained th e intermediate filament protein peripherin, and were labeled by the le ctin BSI, identifying them as neurons likely to have unmyelinated axon s. In addition, small TrkA-negative neurons were extensively labeled b y antibodies to the intermediate filament protein alpha-internexin, th e delta isoform of protein kinase C, and by the BSI isolectin BSI-B-4. In order to assess the potential functions of TrkA-negative small neu rons, we examined their projections to the dorsal horn of the spinal c ord. TrkA-immunoreactivity in the spinal cord was restricted to lamina I and the outer region of lamina II (IIo), similar to staining for ca lcitonin gene-related peptide. In contrast, the central projections of TrkA-negative neurons, as visualized by BSI-B-4 staining,were particu larly dense in lamina IIi. Our results suggest that TrkA-expressing an d non-TrkA-expressing small neurons compose functionally distinct popu lations of DRG neurons. (C) 1996 Wiley-Liss, Inc.