Mammalian somatosensory mechanotransduction

doi:10.1016/j.conb.2009.07.008

Current Opinion in Neurobiology

Volume 19, Issue 4, August 2009, Pages 362-369

https://doi.org/10.1016/j.conb.2009.07.008 Get rights and content

In the mammalian somatosensory system, mechanosensitive neurons mediate the senses of touch and pain. Among sensory modalities, mechanosensation has been the most elusive with regard to the identification of transduction molecules. One factor that has hindered the identification of transduction molecules is the diversity of neurons; physiological studies have revealed many subtypes of neurons, specialized to detect a variety of mechanical stimuli. Do different subtypes use the same transduction molecules that are modified by cellular context? Or, are there multiple mechanotransducers that specialize in sensing different mechanical stimuli? This review highlights recent progress in identifying and characterizing candidate molecular force transducers, as well as the development of new tools to characterize touch transduction at the molecular, cellular, and behavioral levels.

Introduction

The mammalian somatosensory system detects a wide variety of mechanical stimuli. It enables us to differentiate between noxious stimuli, such as a pinprick, and innocuous light touch, such as the brush of a feather. Such discrimination serves an important protective function. Tactile discomfort or pain warns us against harmful stimuli in the environment and evokes protective reflexes. But pain can also be a chronic, debilitating affliction that no longer serves a protective function [1, 2]. Current research in the field of mammalian somatosensory mechanotransduction is focused on several critical questions. What are the molecular force transducers that detect tactile stimuli? How is force sensitivity tuned? How do injury or disease alter mechanical sensitivity? Here we review current papers that address these key questions.

Section snippets

Diversity of mechanosensitive sensory neurons

We encounter many types of mechanical stimuli, such as texture, shape, vibration, or pressure. This variety of stimuli is matched by a diverse array of somatosensory neurons [3, 4]. Somatosensory neurons lie in the dorsal root and trigeminal ganglia, from which they extend sensory afferents, and are classified into three broad groups: C, Aβ, and Aδ fibers (Figure 1). C-fiber nociceptors are unmyelinated (small diameter), terminate as free-nerve endings in target tissues and respond to noxious

Candidate mechanotransduction molecules

Three classes of ion channels have been implicated in mammalian somatosensory mechanotransduction: Degenerin/Epithelial sodium channels (DEG/ENaC), Transient Receptor Potential (TRP) channels and two-pore potassium (KCNK) channels (Table 1). Genetic studies from C. elegans demonstrate a requirement for DEG/ENaC subunits and accessory proteins, such as the stomatin-domain containing MEC-2, in touch responses [11]. Mice lacking the mammalian DEG/ENaC homologs, acid-sensing ion channels (ASIC)

Mechanical hypersensitivity

Hypersensitivity to mechanical stimuli (hyperalgesia) often occurs after tissue damage caused by inflammation, injury, or disease. Both central and peripheral mechanisms contribute to altered mechanical pain thresholds [29] but here we will emphasize recent progress in understanding peripheral changes. Because K⁺ channels play key roles in regulating neuronal excitability, they are suited to be mediators of hyperalgesia. Indeed, altered expression of voltage gated K⁺ channels has been

Cutaneous non-neuronal mechanosensors

While Aβ fibers steal the limelight as primary mechanotransducers of light touch, they are closely associated with specialized structures, including Merkel cells, Pacinian corpuscles, Meissner corpuscles, and hair follicles [43]. Even ‘free’ nerve endings are embedded in keratinocytes. Thus, it is possible that these non-neuronal cells and corpuscles act as the primary mechanotransducers and that sensory afferents are activated through secreted signaling molecules. Definitive data for such a

New cellular-based assays to probe mechanotransduction in vitro

Thus far, it has not been possible to record mechanotransduction currents in intact mammalian sensory neurons in vivo. Thus, there is much interest in developing robust, in vitro assays that measure transduction currents with the same properties of the transduction apparatus in vivo. Traditionally, mechanotransduction has been studied in vitro by applying pressure to a patch pipette during electrophysiological recording, or by focal displacement of cell somata using glass probes (Figure 2d).

Conclusion

Among sensory modalities, mechanosensation has been the most elusive with regard to the identification of molecules that mediate stimulus transduction. This reflects the relative paucity and heterogeneity of mechanoreceptive cells and the lack of in vitro and in vivo systems for analyzing native mechanosensory responses. In the last few years there has been an increase in the number of candidate mechanotransduction channels. Pardoxically, transgenic mice lacking these candidates often display

Acknowledgements

We thank Ms. Kristin Gerhold for essential comments on the manuscript and helpful discussions. Work in the Bautista lab is supported by a Career Award in Biosciences from the Burroughs Welcome Fund and a fellowship from the Alfred P Sloan Foundation.

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Mammalian somatosensory mechanotransduction

Introduction

Section snippets

Diversity of mechanosensitive sensory neurons

Candidate mechanotransduction molecules

Mechanical hypersensitivity

Cutaneous non-neuronal mechanosensors

New cellular-based assays to probe mechanotransduction in vitro

Conclusion

Acknowledgements

Curr Opin Neurobiol

Trends Neurosci

Neuron

J Biol Chem

Neuron

Cell

Neuron

Brain Res Mol Brain Res

Neuron

Neuroscience

J Biol Chem

Mol Pain

Neuroscience

J Biol Chem

Neurosci Lett

Neuron

J Neurosci Methods

Neurosci Lett

Pain

J Biol Chem

The diagnosis and management of neuropathic pain in daily practice in Belgium: an observational study

BMC Public Health

Neuropathic pain

Curr Opin Neurobiol

Mechanosensation and pain

J Neurobiol

A T-type calcium channel required for normal function of a mammalian mechanoreceptor

Nat Neurosci

Atypical expansion in mice of the sensory neuron-specific Mrg G protein-coupled receptor family

Proc Natl Acad Sci U S A

Molecular genetic visualization of a rare subset of unmyelinated sensory neurons that may detect gentle touch

Nat Neurosci

The cell and molecular basis of mechanical, cold, and inflammatory pain

Science

Neurosensory mechanotransduction

Nat Rev Mol Cell Biol

A stomatin-domain protein essential for touch sensation in the mouse

Nature

TRP channels in mechanosensation: direct or indirect activation?

Nat Rev Neurosci

Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1

Nature

Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing

J Neurosci