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Review
. 2020 Apr;127(4):527-540.
doi: 10.1007/s00702-020-02162-6. Epub 2020 Feb 27.

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

Alain Artola  1 , Daniel Voisin  2 , Radhouane Dallel  3
Affiliations
Review

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

Alain Artola et al. J Neural Transm (Vienna). 2020 Apr.

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.

Keywords: Chronic pain; Dorsal horn; Mechanical allodynia; PKCγ; Spinal; Trigeminal.

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