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Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2270-5. doi: 10.1073/pnas.1600418113. Epub 2016 Feb 8.

Pathophysiological implication of CaV3.1 T-type Ca2+ channels in trigeminal neuropathic pain.

Author information

1
Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY 10016; Marine Biological Laboratory, Woods Hole, MA 02543;
2
Center for Neural Science, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
3
Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY 10016; Marine Biological Laboratory, Woods Hole, MA 02543; rodolfo.llinas@nyumc.org.

Abstract

A crucial pathophysiological issue concerning central neuropathic pain is the modification of sensory processing by abnormally increased low-frequency brain rhythms. Here we explore the molecular mechanisms responsible for such abnormal rhythmicity and its relation to neuropathic pain syndrome. Toward this aim, we investigated the behavioral and electrophysiological consequences of trigeminal neuropathic pain following infraorbital nerve ligations in CaV3.1 T-type Ca(2+) channel knockout and wild-type mice. CaV3.1 knockout mice had decreased mechanical hypersensitivity and reduced low-frequency rhythms in the primary somatosensory cortex and related thalamic nuclei than wild-type mice. Lateral inhibition of gamma rhythm in primary somatosensory cortex layer 4, reflecting intact sensory contrast, was present in knockout mice but severely impaired in wild-type mice. Moreover, cross-frequency coupling between low-frequency and gamma rhythms, which may serve in sensory processing, was pronounced in wild-type mice but not in CaV3.1 knockout mice. Our results suggest that the presence of CaV3.1 channels is a key element in the pathophysiology of trigeminal neuropathic pain.

KEYWORDS:

central pain; cross-frequency coupling; lateral inhibition; thalamocortical dysrhythmia

PMID:
26858455
PMCID:
PMC4776481
DOI:
10.1073/pnas.1600418113
[Indexed for MEDLINE]
Free PMC Article

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