Trends in Neurosciences
ReviewGetting in Touch with Mechanical Pain Mechanisms
Section snippets
Pain Is Essential
The survival of all organisms (plants, animals, fungi, microbes) depends on their ability to detect and respond to a wide variety of external stimuli. Chemicals, temperature, mechanical force, and pH are all cues that can indicate a safe or dangerous environment. While nearly all cells possess some ability to sense and respond to these cues, most multicellular animals have a nervous system that is specialized to detect and transduce signals, perform computation, and generate responses to a wide
Recent Studies Identified Molecularly Defined Subpopulations of Mechanonociceptors
Multiple theories attempt to explain how somatosensory modalities are distinguished peripherally and centrally. Of these, the ‘labeled line’ theory of somatosensation [1., 2., 3., 4.] has gained traction, from the study of mutant mice deficient in ion channels and receptors that transduce specific stimuli and from ablation studies where specific subpopulations of neurons are selectively destroyed using chemical or genetic tools. For example, such approaches have identified a peripheral labeled
Modulators and Transducers of Mechanical Nociception
Molecular transducers of noxious mechanical force have been definitively identified only in invertebrate model organisms, including the nematode C. elegans and the fruit fly Drosophila melanogaster. The transduction molecules that have been identified include the degenerin/Epithelial Sodium Channel (DEG/ENaC) DEG-1/MEC-4 in worms [40] and the Transient Receptor Potential (TRP) channel painless along with the mechanosensitive channel piezo in flies [41., 42., 43., 44., 45.]. It was initially
Drawing the Line: Innocuous versus Noxious Touch
The ability to distinguish between painful and nonpainful mechanical stimuli in animal models is essential for studying mechanonociception. In human studies, asking the subject or providing a standardized pain questionnaire may be sufficient to make the distinction [69., 70., 71., 72.]. By contrast, the gold standard for assessing mechanical pain sensitivity in rats and mice has been and still remains the von Frey filament assay (see details next) [73]. In fact, the major advantage of the von
Concluding Remarks and Future Perspectives
Much progress has been made in demystifying the cells and molecules of mechanical pain. However, several important questions remain to be answered (see Outstanding Questions). First and foremost, the identities of the noxious mechanotransducer(s) in mammalian somatosensory neurons remain poorly understood. Furthermore, the pain field has mostly focused on cutaneous pain, although many diseases of the internal organs including pancreatitis, gastrointestinal disorders, arthritis, and bone cancer
Acknowledgments
We would like to thank S. Mali (UC Berkeley), K. Marshall, and I. Daou (The Scripps Research Institute) for critical comments on the manuscript. D.M.B. is supported by the NIH (AR059385; NS07224 and NS098097) and the Howard Hughes Medical Institute.
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2023, Journal of Investigative DermatologyCitation Excerpt :Mechanoreceptors that conduct mechanical pain are called the high-threshold mechanoreceptors or mechanonociceptors, whereas mechanoreceptors that respond to innocuous mechanical stimuli (touch) are called the low-threshold mechanoreceptors or touch receptors (Handler and Ginty, 2021). Aδ fibers are the main class of mechanonociceptors (high-threshold mechanoreceptors) and signal fast pain (Hill and Bautista, 2020). C fibers constitute the rest of the mechanonociceptors and trigger slow pain.
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Present address: Department of Neuroscience, Scripps Research, La Jolla, CA 92037, USA