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The brain-penetrant 5-HT7 receptor agonist LP-211 reduces the sensory and affective components of neuropathic pain

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Santello Mirko, Bisco Alberto, Nevian Natalie Elisabeth, Lacivita Enza, Leopoldo Marcello, Nevian Thomas,
Project Cortical mechanisms controlling migraine pain
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Original article (peer-reviewed)

Journal Neurobiology of Disease
Publisher Elsevier
Volume (Issue) 106
Page(s) 214 - 221
Title of proceedings Neurobiology of Disease
DOI 10.1016/j.nbd.2017.07.005

Open Access

Abstract

Neuropathic pain is a debilitating pathological condition of high clinical relevance. Changes in neuronal excitability in the anterior cingulate cortex (ACC) play a central role in the negative emotional and affective aspects of chronic pain. We evaluated the effects of LP-211, a new serotonin-receptor-type-7 (5-HT 7 R) agonist that crosses the blood-brain barrier, on ACC neurons in a mouse model of neuropathic pain. LP-211 reduced synaptic integration in layer 5 pyramidal neurons, which was enhanced in neuropathic pain due to a dysfunction of dendritic hyperpolarization-activated-and-cyclic-nucleotide-regulated (HCN) channels. Acute injection of LP-211 had an analgesic effect, increasing the mechanical withdrawal threshold in neuropathic animals, which was partially mediated by an action in the ACC. Additionally, the acute application of LP-211 blocked the switch in the place escape/avoidance behavior induced by noxious stimuli. Thus systemic treatment with a 5-HT 7 R agonist leads to modulation of the ACC, which dampens sensory and affective aspects of chronic pain.
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