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PKCγ interneurons, a gateway to pathological pain in the dorsal horn

  • Neurology and Preclinical Neurological Studies - Review Article
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Abstract

Chronic pain is a frequent and disabling condition that is significantly maintained by central sensitization, which results in pathological amplification of responses to noxious and innocuous stimuli. As such, mechanical allodynia, or pain in response to a tactile stimulus that does not normally provoke pain, is a cardinal feature of chronic pain. Recent evidence suggests that the dorsal horn excitatory interneurons that express the γ isoform of protein kinase C (PKCγ) play a critical role in the mechanism of mechanical allodynia during chronic pain. Here, we review this evidence as well as the main aspects of the development, anatomy, electrophysiology, inputs, outputs, and pathophysiology of dorsal horn PKCγ neurons. Primary afferent high-threshold neurons transmit the nociceptive message to the dorsal horn of the spinal cord and trigeminal system where it activates second-order nociceptive neurons relaying the information to the brain. In physiological conditions, low-threshold mechanoreceptor inputs activate inhibitory interneurons in the dorsal horn, which may control activation of second-order nociceptive neurons. During chronic pain, low-threshold mechanoreceptor inputs now activate PKCγ neurons that forward the message to second-order nociceptive neurons, turning thus tactile inputs into pain. Several mechanisms may contribute to opening this gate, including disinhibition, activation of local astrocytes, release of diffusible factors such as reactive oxygen species, and alteration of the descending serotoninergic control on PKCγ neurons through 5-HT2A serotonin receptors. Dorsal horn PKCγ neurons, therefore, appear as a relevant therapeutic target to alleviate mechanical allodynia during chronic pain.

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Acknowledgements

This work was supported by funding from the Institut National de la Santé et de la Recherche Médicale (INSERM), Université Clermont Auvergne (UCA), Région Auvergne-Rhône-Alpes and CHU Clermont-Ferrand (France).

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  1. Université Clermont Auvergne, CHU Clermont-Ferrand, Inserm, Neuro-Dol, 63000, Clermont-Ferrand, France

    Alain Artola & Radhouane Dallel

  2. Université de Bordeaux, Inserm, Neurocentre Magendie, 33000, Bordeaux, France

    Daniel Voisin

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Artola, A., Voisin, D. & Dallel, R. PKCγ interneurons, a gateway to pathological pain in the dorsal horn. J Neural Transm 127, 527–540 (2020). https://doi.org/10.1007/s00702-020-02162-6

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