"How is it possible to feel different sensations from the same area on the skin? Althoughvery basic, there are still fundamental questions like this, that remain to be answered on thetopic of sensory perception. One of the more prominent theories on how the nervous systemsolves the sensory discrimination dilemma is the "labeled line" or "specificity" theory whichclaims dedicated compartments of the system, e.g. marked peripheral afferent subpopulations, are responsible for specific sensory modalities. If proven accurate, this model inspires"compartmentalized therapy" which aims to alleviate sensory diseases through targetingspecific elements responsible for individual modalities, like pain or itch. In contrast, if multiplemodalities share similar elements of the sensory system, compartmentally targeting suchflexible system can lead to compensatory modulation of other compartments leading toinefficacy of the therapeutic approach. Although the debate on specificity versus multimodalityis ongoing in the field of sensory biology, in the recent years, absence of evidence formultimodality in certain specific genetic and behavioral studies has been interpreted asevidence of absence. Here, I will propose that the failure to detect evidence of multiplecompartments' contribution to diverse modalities is due to overlooked technical limitations. Limitation of common approaches such as animal sensory behavioral assays, optogenetics, chemogenetics, and single time point snapshot transcriptomic tools such as single cell RNAsequencing may have led us to believe that compartments not tuned for a specific modality aredispensable for that sensation. In this dissertation, with the aim to iterate the need for wholesome approaches in sensorybiology, I will bring convincing evidence for functional dynamism and genetic heterogeneity inthe peripheral primary sensory system. In the first data chapter (Chapter 2) I will focus onmultimodal capacity of a subset of primary afferents to prove a single population of neuronscan contribute to transmission of different senses, itch and pain. I will also introduce molecularplayers that are involved in modulation of the signals in a modality specific manner, i.e.engagement of TRP channels in itch but not pain transmission through MRGPRA3 expressingafferents. In the second data chapter (Chapter 3), with multimodality in mind, I will provideelements of a single-cell transcriptomic atlas of human primary sensory ganglia. Takingadvantage of single-nucleus RNA and ATAC sequencing, I lay down how multiple functionalpathways are expressed in single neuronal populations of human dorsal root ganglia. Asimportant contributors to sensory coding in health and disease, information of thetranscriptomic and genomic repertoire of non-neuronal ganglia resident cells will also beincluded in this chapter. I trust that this dissertation will highlight the necessity of recognizing technical pitfalls insensory research, particularly pain related studies. I also hope to assert the importance ofmultimodality and to build a solid base for more wholesome research that can lead to a betterunderstanding of sensory discrimination mechanisms"--