Dysfunction of Cortical Dendritic Integration in Neuropathic Pain Reversed by Serotoninergic Neuromodulation

Santello, Mirko; Nevian, Thomas (2015). Dysfunction of Cortical Dendritic Integration in Neuropathic Pain Reversed by Serotoninergic Neuromodulation. Neuron, 86(1), pp. 233-246. Cell Press 10.1016/j.neuron.2015.03.003

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Neuropathic pain is caused by long-term modifications of neuronal function in the peripheral nervous system, the spinal cord, and supraspinal areas. Although functional changes in the forebrain are thought to contribute to the development of persistent pain, their significance and precise subcellular nature remain unexplored. Using somatic and dendritic whole-cell patch-clamp recordings from neurons in the anterior cingulate cortex, we discovered that sciatic nerve injury caused an activity-dependent dysfunction of hyperpolarization-activated cyclic nucleotide-regulated (HCN) channels in the dendrites of layer 5 pyramidal neurons resulting in enhanced integration of excitatory postsynaptic inputs and increased neuronal firing. Specific activation of the serotonin receptor type 7 (5-HT7R) alleviated the lesion-induced pathology by increasing HCN channel function, restoring normal dendritic integration, and reducing mechanical pain hypersensitivity in nerve-injured animals in vivo. Thus, serotoninergic neuromodulation at the forebrain level can reverse the dendritic dysfunction induced by neuropathic pain and may represent a potential therapeutical target.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology
10 Strategic Research Centers > Center for Cognition, Learning and Memory (CCLM)

UniBE Contributor:

Santello, Mirko and Nevian, Thomas

Subjects:

500 Science
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0896-6273

Publisher:

Cell Press

Language:

English

Submitter:

Simon Ruch

Date Deposited:

27 Jul 2015 14:09

Last Modified:

22 Oct 2015 10:08

Publisher DOI:

10.1016/j.neuron.2015.03.003

PubMed ID:

25819610

BORIS DOI:

10.7892/boris.70473

URI:

https://boris.unibe.ch/id/eprint/70473

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