Sensory neurons with cell bodies situated in dorsal root ganglia convey information from external or internal sites of the body such as actual or potential harm, temperature or muscle length to the central nervous system. In recent years, large investigative efforts have worked toward an understanding of different types of DRG neurons at transcriptional, translational, and functional levels. These studies most commonly rely on data obtained from laboratory animals. Human DRG, however, have received far less investigative focus over the last 30 years. Nevertheless, knowledge about human sensory neurons is critical for a translational research approach and future therapeutic development. This review aims to summarize both historical and emerging information about the size and location of human DRG, and highlight advances in the understanding of the neurochemical characteristics of human DRG neurons, in particular nociceptive neurons.

Background:The mechanism by which the p75 neurotrophin receptor (p75 NTR ) and TrkA interact to enhance neurotrophin signaling is unknown. Results: The p75NTR intracellular domain fragment, p75 ICD , but not full-length p75 NTR enhanced NGF binding to TrkA and neurite outgrowth. Conclusion:The results suggest that p75 ICD causes a conformational change within the extracellular domain of TrkA. Significance: The findings challenge our current understanding of how p75 NTR enhances neurotrophic activity.

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The common neurotrophin receptor (p75(NTR) ) regulates various functions in the developing and adult nervous system. Cell survival, cell death, axonal and growth cone retraction, and regulation of the cell cycle can be regulated by p75(NTR) -mediated signals following activation by either mature or pro-neurotrophins and in combination with various co-receptors, including Trk receptors and sortilin. Here, we review the known functions of p75(NTR) by cell type, receptor-ligand combination, and whether regulated intra-membrane proteolysis of p75(NTR) is required for signalling. We highlight that the generation of the intracellular domain fragment of p75(NTR) is associated with many of the receptor functions, regardless of its ligand and co-receptor interactions.

Background: Sortilin and p75NTR induce neuronal apoptosis by binding pro-neurotrophins during development and following neuronal injury. Results: Sortilin interacts with an extracellular juxtamembrane 23-amino acid sequence of p75 NTR . Conclusion: Despite binding being mediated through extracellular interactions, the intracellular domain of sortilin regulates p75 NTR shedding and apoptosis. Significance: Mapping may allow design of compounds inhibiting neuronal cell death by blocking the interaction between sortilin and p75 NTR .