Biology subjects

Bouchatta, O.

Publications and source records attributed to Bouchatta, O..

3 recordsLinked to original sources

bioRxiv2023

PIEZO2-dependent rapid pain system in humans and mice.

The PIEZO2 ion channel is critical for transducing light touch into neural signals but is not considered necessary for transducing acute pain in humans. Here, we discovered an exception - a form of mechanical pain evoked by hair pulling. Based on observations in a rare group of individuals with PIEZO2 deficiency syndrome, we demonstrated that hair-pull pain is dependent on PIEZO2 transduction. Studies in control participants showed that hair-pull pain triggered a distinct nocifensive response, including a nociceptive reflex. Observations in rare A{beta} deafferented individuals and nerve conduction block studies in control participants revealed that hair-pull pain perception is dependent on A{beta} input. Single-unit axonal recordings revealed that a class of cooling-responsive myelinated nociceptors in human skin is selectively tuned to painful hair-pull stimuli. Further, we pharmacologically mapped these nociceptors to a specific transcriptomic class. Finally, using functional imaging in mice, we demonstrated that in a homologous nociceptor, Piezo2 is necessary for high-sensitivity, robust activation by hair-pull stimuli. Together, we have demonstrated that hair-pulling evokes a distinct type of pain with conserved behavioral, neural, and molecular features across humans and mice.

neuroscience↗

bioRxiv2023

Human foot outperforms the hand in mechanical pain discrimination

Tactile discrimination has been extensively studied, but mechanical pain discrimination remains poorly characterised. Here, we measured the capacity for mechanical pain discrimination using a twoalternative forced choice paradigm, with force-calibrated indentation stimuli (Semmes-Weinstein monofilaments) applied to the hand and foot dorsa of healthy human volunteers. In order to characterise the relationship between peripheral neural and perceptual processes, we recorded singleunit activity from myelinated (A) and unmyelinated (C) mechanosensitive nociceptors in the skin using microneurography. At the perceptual level, we found that the foot was better at discriminating noxious forces than the hand, which stands in contrast to that for innocuous force discrimination, where the hand performed better than the foot. This observation of superior mechanical pain discrimination on the foot compared to the hand could not be explained by the responsiveness of single primary afferents. We found no significant difference in the discrimination performance of either the myelinated or unmyelinated class of nociceptors between skin regions. This suggests the possibility that other factors such as skin biophysics, receptor density or central mechanisms may underlie these regional differences. Significance StatementStandard clinical practice for diagnosing neuropathies and pain disorders often involves assessing thresholds for pain or light touch. The ability to discriminate between different stimulus intensities is a separate but equally important sensory function, however this is not typically assessed in the clinic, and so studying this may provide insights into pain signalling mechanisms. Here, we investigated the ability of healthy individuals to discriminate between different forces of painful indentation. We found that the foot was better at this than the hand. This difference could not be explained by the firing activity of peripheral nociceptors (pain-signalling neurons) between the two regions, suggesting that mechanisms other than nociceptor sensitivity are involved.

neuroscience↗

bioRxiv2023

Single-Soma Deep RNA sequencing of Human DRG Neurons Reveals Novel Molecular and Cellular Mechanisms Underlying Somatosensation

The versatility of somatosensation arises from heterogeneous dorsal root ganglion (DRG) neurons. However, soma transcriptomes of individual human DRG (hDRG) neurons - critical information to decipher their functions - are lacking due to technical difficulties. Here, we developed a novel approach to isolate individual hDRG neuron somas for deep RNA sequencing (RNA-seq). On average, >9,000 unique genes per neuron were detected, and 16 neuronal types were identified. Cross-species analyses revealed remarkable divergence among pain-sensing neurons and the existence of human-specific nociceptor types. Our deep RNA-seq dataset was especially powerful for providing insight into the molecular mechanisms underlying human somatosensation and identifying high potential novel drug targets. Our dataset also guided the selection of molecular markers to visualize different types of human afferents and the discovery of novel functional properties using single-cell in vivo electrophysiological recordings. In summary, by employing a novel soma sequencing method, we generated an unprecedented hDRG neuron atlas, providing new insights into human somatosensation, establishing a critical foundation for translational work, and clarifying human species-specific properties.

neuroscience↗