PKCγ interneurons, a gateway to pathological pain in the dorsal horn
- 27 February 2020
- journal article
- review article
- Published by Springer Science and Business Media LLC in Journal of Neural Transmission
- Vol. 127 (4), 527-540
- https://doi.org/10.1007/s00702-020-02162-6
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
This publication has 137 references indexed in Scilit:
- The Functional Organization of Cutaneous Low-Threshold Mechanosensory NeuronsCell, 2011
- Isozyme-specific Effects of Protein Kinase C in Pain ModulationAnesthesiology, 2011
- Reactive oxygen species contribute to neuropathic pain by reducing spinal GABA releasePain, 2011
- Quantitative study of NPY‐expressing GABAergic neurons and axons in rat spinal dorsal hornJournal of Comparative Neurology, 2011
- Neuronal circuitry for pain processing in the dorsal hornNature Reviews Neuroscience, 2010
- Populations of inhibitory and excitatory interneurons in lamina II of the adult rat spinal dorsal horn revealed by a combined electrophysiological and anatomical approachPain, 2010
- Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptorsNature, 2009
- Cellular and Molecular Mechanisms of PainCell, 2009
- Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural PlasticityThe Journal of Pain, 2009
- Oxidative stress in the spinal cord is an important contributor in capsaicin-induced mechanical secondary hyperalgesia in micePain, 2008