Mechanical Pain Evoked by Single Hair Pulling Relies on Aβ-fiber

Mechanical Pain Evoked by Single Hair Pulling Relies on Aβ-fiber Conduction and PIEZO2 Transduction. -SA143

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Day 3: 9:45 poster sessions

Abstract Description

This presentation will provide different reflections on pain. Identification of molecular receptors of somatosensory neurons, including the TRP and PIEZO channels (Nobel Prize in 2021), has had a major impact.

We will show here how the peripheral nervous system, including specialized cells, responds to unitary hair pull pain (HPP) stimuli. It is a fundamental question that will help us as researchers and clinicians better understand how pain is encoded at a primary afferent level. The Aβ high-threshold mechanoreceptor is a novel peripheral substrate, not reported before in humans until our lab's recent work (Nagi et al. 2019). We have now discovered a subtype of Aβ high-threshold mechanoreceptor that signals hair-pulling pain in humans. Interestingly, such a population also exists in macaque and mice, and we found that the mechanotransduction channel PIEZO2 plays a crucial role in setting sensitivity of HPP nociceptors.
Background: We previously published that noxious skin indentation can be signaled by “ultrafast” Aβ high-threshold mechanoreceptors and do not depend on the mechanotransduction channel PIEZO2 in humans.

Objective: Here, we investigated the mechanisms of mechanical pain transduction and coding evoked by hair pulling in humans.

Methods: To address this, first, we conducted psychophysical experiments by testing a range of pulling forces on single hairs in healthy participants and patients with PIEZO2 deficiency syndrome. We then performed a preferential ischemic nerve block to investigate the contributions of primary afferents to hair-pulling pain. Next, we used in vivo electrophysiological recordings (microneurography) from single mechanoreceptive cutaneous neurons to investigate the neural coding of single hair pulls.

Results and Conclusions: We found hair-pulling elicits a distinct, low-threshold pain sensation associated with a specific urge-to-move behavior. Interestingly, patients with PIEZO2 deficiency syndrome had a deficit in pain perception to hair-pulling stimuli. Hair-pulling pain was abolished in the condition of blocked Aβ fibers – a finding confirmed in selective Aβ deafferented patients who did not perceive hair-pulling stimuli as painful. A class of Aβ high-threshold mechanoreceptors showed selective tuning to painful hair pull stimuli.
These findings suggest that hair-pulling pain is a specialized ultrasensitive system that relies on Aβ-fiber conduction and PIEZO2 transduction and is encoded by a distinct class of Aβ high-threshold mechanoreceptors in human skin.

Presenters

Mr Otmane Bouchatta

Authors

Otmane Bouchatta - Linköping University (Sweden) , Marek Brodzki - Linköping University (Sweden) , Andrew Marshall G - University of Liverpool (UK) , Oumie Thorell - Linköping University (Sweden) , Emma Kindström - Linköping University (Sweden) , Kevin Ng - Linköping University (Sweden) , Jaquette Liljencrantz - University of Gothenburg (Sweden) , Eleni Frangos - National Center for Complementary and Integrative Health, NIH (USA) , Dimah Saade - National Institute of Neurological Disorders and Stroke, NIH (USA) , Gabriela Carballo - Linköping University (Sweden) , Houria Manouze - Linköping University (Sweden) , Carsten Bönneman G - National Institute of Neurological Disorders and Stroke, NIH (USA) , Alexander Chesler T - National Center for Complementary and Integrative Health, NIH (USA) , Håkan Olausson - Linköping University (Sweden) , Marcin Szczot - Linköping University (Sweden) , Saad Nagi S - Linköping University (Sweden)

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Mechanical Pain Evoked by Single Hair Pulling Relies on Aβ-fiber Conduction and PIEZO2 Transduction. -SA143

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Abstract Description

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