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Activation of cortical somatostatin interneurons prevents the development of neuropathic pain.
- Source :
-
Nature neuroscience [Nat Neurosci] 2017 Aug; Vol. 20 (8), pp. 1122-1132. Date of Electronic Publication: 2017 Jun 26. - Publication Year :
- 2017
-
Abstract
- Neuropathic pain involves long-lasting modifications of pain pathways that result in abnormal cortical activity. How cortical circuits are altered and contribute to the intense sensation associated with allodynia is unclear. Here we report a persistent elevation of layer V pyramidal neuron activity in the somatosensory cortex of a mouse model of neuropathic pain. This enhanced pyramidal neuron activity was caused in part by increases of synaptic activity and NMDA-receptor-dependent calcium spikes in apical tuft dendrites. Furthermore, local inhibitory interneuron networks shifted their activity in favor of pyramidal neuron hyperactivity: somatostatin-expressing and parvalbumin-expressing inhibitory neurons reduced their activity, whereas vasoactive intestinal polypeptide-expressing interneurons increased their activity. Pharmacogenetic activation of somatostatin-expressing cells reduced pyramidal neuron hyperactivity and reversed mechanical allodynia. These findings reveal cortical circuit changes that arise during the development of neuropathic pain and identify the activation of specific cortical interneurons as therapeutic targets for chronic pain treatment.
- Subjects :
- Action Potentials physiology
Animals
Dendrites metabolism
Mice, Transgenic
Neuralgia metabolism
Receptors, N-Methyl-D-Aspartate metabolism
Somatosensory Cortex physiology
Vasoactive Intestinal Peptide metabolism
Interneurons physiology
Nerve Net physiopathology
Neuralgia physiopathology
Pyramidal Cells physiology
Somatosensory Cortex physiopathology
Somatostatin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1546-1726
- Volume :
- 20
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Nature neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 28671692
- Full Text :
- https://doi.org/10.1038/nn.4595