title: T-type calcium channel blocker Z944 restores cortical synchrony and thalamocortical connectivity in a rat model of neuropathic pain.
abstract: Oscillations are fundamental to communication between neuronal ensembles. We previously reported that pain in awake rats enhances synchrony in primary somatosensory cortex (S1) and attenuates coherence between S1 and ventral posterolateral (VPL) thalamus. Here, we asked whether similar changes occur in anesthetized rats and whether pain modulates phase-amplitude coupling between VPL and S1. We also hypothesized that the suppression of burst firing in VPL using Z944, a novel T-type calcium channel blocker, restores S1 synchrony and thalamocortical connectivity. Local field potentials were recorded from S1 and VPL in anesthetized rats 7 days after sciatic chronic constriction injury (CCI). In rats with CCI, low-frequency (4-12 Hz) synchrony in S1 was enhanced, whereas VPL-S1 coherence and theta-gamma phase-amplitude coupling were attenuated. Moreover, Granger causality showed decreased informational flow from VPL to S1. Systemic or intrathalamic delivery of Z944 to rats with CCI normalized these changes. Systemic Z944 also reversed thermal hyperalgesia and conditioned place preference. These data suggest that pain-induced cortical synchrony and thalamocortical disconnectivity are directly related to burst firing in VPL.
authors.affiliation: Department of Neurosurgery, Rhode Island Hospital, and Department of Neuroscience, Brown University, Providence, RI, USA Graduate Institute of Electronics Engineering, National Taiwan University, Taipei, Taiwan Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China Research & Translational Medicine, Zalicus Inc, Cambridge, MA, USA Neuromodulation Research, Medtronic Inc, Minneapolis, MN, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: LeBlanc
authors.forename: Theresa R
authors.initials: TR
authors.lastname: Lii
authors.forename: Jian Jia
authors.initials: JJ
authors.lastname: Huang
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Chao
authors.forename: Paul M
authors.initials: PM
authors.lastname: Bowary
authors.forename: Brent S
authors.initials: BS
authors.lastname: Cross
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Lee
authors.forename: Louis P
authors.initials: LP
authors.lastname: Vera-Portocarrero
authors.forename: Carl Y
authors.initials: CY
authors.lastname: Saab
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020747:Calcium Channels, T-Type; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009437:Neuralgia / Q000503:physiopathology*; D010880:Piperidines; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000081:Acetamides; D001549:Benzamides; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D010880:Piperidines; C000629485:Z944