Human touch stimulates 16 different types of nerve cells in the body

The human sense of touch is a complex system that integrates diverse sensations such as pain, temperature, and pleasant contact. Recent research has provided groundbreaking insights into the molecular and functional diversity of the neurons responsible for somatosensation.

Scientists have identified no less than 16 distinct types of nerve cells in the human dorsal root ganglion (DRG), significantly expanding our understanding of how the human nervous system operates.

This research, published in the journal, Nature Neuroscience, marks a milestone in neuroscience, as it is the first to comprehensively map the molecular profiles of individual human DRG neurons.

Employing deep RNA sequencing (RNA-seq), researchers detected over 9,000 unique genes per neuron. This robust dataset enabled the classification of human DRG neurons into 16 types based on their gene expression profiles.

According to Associate Professor Wenqin Luo from the University of Pennsylvania, “This study provides a landscape view of the human sense of touch.”

The findings challenge traditional models suggesting that each neuron type is specialized for a single sensation. Instead, the data reveal that neurons often respond to multiple stimuli, suggesting a more integrated and dynamic sensory system.

Comparative analyses with mice and macaques uncovered both shared and distinct features among species. For example, humans possess a higher proportion of rapidly conducting pain-sensing neurons, a feature that likely reflects adaptations for larger body sizes.

As Håkan Olausson, Professor at Linköping University, explained, “In humans, the distances are greater, and the signals need to be sent to the brain more rapidly; otherwise, you’d be injured before you even react and withdraw.”

Mapping the molecular profiles of DRG neurons was a formidable challenge. Human DRG neurons are particularly large and prone to damage during isolation, making them difficult to study using traditional methods. Researchers overcame these obstacles by isolating individual neuronal somata and conducting single-soma RNA-seq.

This technique not only preserved the integrity of the neurons but also provided a high-resolution view of their transcriptomes. Spatial transcriptomics and RNAscope in situ hybridization further validated the findings, ensuring the accuracy and reproducibility of the data.

These advanced methods have implications far beyond basic research. The study’s atlas of DRG neurons serves as a foundation for translational work aimed at addressing chronic pain and other sensory disorders.

Current treatments often fail to translate effectively from animal models to humans due to significant differences in neuronal types and molecular profiles. By bridging this gap, the new research opens the door to more effective, targeted therapies.

One of the most surprising findings involved neurons previously thought to be specialized for specific sensations. For instance, a type of neuron associated with pleasant touch also responded to capsaicin, the chemical that gives chili peppers their heat, and to changes in temperature. These responses suggest an integrated sensory pathway that combines signals for multiple sensations.

As Håkan Olausson noted, “For ten years, we’ve been listening to the nerve signals from these nerve cells, but we had no idea about their molecular characteristics. In this study, we see what type of proteins these nerve cells express as well as what kind of stimulation they can respond to, and now we can link it. It’s a huge step forward.”

Another notable discovery involved pain-sensing neurons that also responded to non-painful cooling and menthol. This finding challenges the conventional view of nerve cells as highly specialized and instead highlights their versatile roles in sensory perception.

According to Saad Nagi, Associate Professor at Linköping University, “There’s a common perception that nerve cells are very specific. But we see that it’s a lot more complicated than that.”

The study underscores the importance of understanding human-specific neuronal types to develop effective medical treatments. Many of the findings from this research cannot be replicated in animal models, underscoring the limitations of relying on non-human data.

For example, rapidly conducting pain-sensing neurons identified in humans were found to be much less prevalent in mice. This discrepancy may explain why some pain treatments that work in animal models fail in clinical trials.

Additionally, the identification of neurons that integrate multiple sensory inputs could lead to novel therapies for sensory disorders. By targeting these integrated pathways, researchers may develop treatments that address not just pain but also its interactions with other sensations, such as temperature and touch.

The collaborative effort between research groups at Linköping University, Karolinska Institutet, and the University of Pennsylvania exemplifies the power of interdisciplinary science. Financial support from organizations like the National Institutes of Health and the Knut and Alice Wallenberg Foundation highlights the global investment in understanding human health.

The researchers anticipate that as more neurons are analyzed, additional types will be identified, further enriching the DRG atlas. This work provides a template for future studies aiming to link molecular profiles with neuronal functions.

The potential for discovery extends to uncovering unknown mechanisms, such as how certain neurons detect cold without expressing known cold-sensitive proteins. Such findings could revolutionize our understanding of sensory biology and lead to breakthroughs in medicine.

As science continues to uncover the complexities of the human sensory system, studies like this not only enhance our fundamental knowledge but also pave the way for transformative clinical applications.

The human sense of touch, once thought to be well understood, now appears more intricate and interconnected than ever before.

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