Molecular mechanisms of nociception

Abstract

The sensation of pain alerts us to real or impending injury and triggers appropriate protective responses. Unfortunately, pain often outlives its usefulness as a warning system and instead becomes chronic and debilitating. This transition to a chronic phase involves changes within the spinal cord and brain, but there is also remarkable modulation where pain messages are initiated — at the level of the primary sensory neuron. Efforts to determine how these neurons detect pain-producing stimuli of a thermal, mechanical or chemical nature have revealed new signalling mechanisms and brought us closer to understanding the molecular events that facilitate transitions from acute to persistent pain.

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Figure 1: Different nociceptors detect different types of pain.
Figure 2: Polymodal nociceptors use a greater diversity of signal-transduction mechanisms to detect physiological stimuli than do primary sensory neurons in other systems.
Figure 3: The molecular complexity of the primary afferent nociceptor is illustrated by its response to inflammatory mediators released at the site of tissue injury.
Figure 4: When nociceptors are exposed to products of injury and inflammation, their excitability is altered by a variety of intracellular signalling pathways.
Figure 5: An alignment of natural and synthetic vanilloid receptor agonists illustrates their structural similarity.

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Acknowledgements

This work was supported by NIH, NIMH and an unrestricted grant from Bristol-Myers Squibb.

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Correspondence to David Julius.

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Julius, D., Basbaum, A. Molecular mechanisms of nociception. Nature 413, 203–210 (2001). https://doi.org/10.1038/35093019

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