Motor cortex stimulation suppresses cortical responses to noxious hindpaw stimulation after spinal cord lesion in rats.
BACKGROUND
Motor cortex stimulation (MCS) is a potentially effective treatment for chronic neuropathic pain. The neural mechanisms underlying the reduction of hyperalgesia and allodynia after MCS are not completely understood.


OBJECTIVE
To investigate the neural mechanisms responsible for analgesic effects after MCS. We test the hypothesis that MCS attenuates evoked blood oxygen-level dependent signals in cortical areas involved in nociceptive processing in an animal model of chronic neuropathic pain.


METHODS
We used adult female Sprague-Dawley rats (n = 10) that received unilateral electrolytic lesions of the right spinal cord at the level of C6 (SCL animals). In these animals, we performed magnetic resonance imaging (fMRI) experiments to study the analgesic effects of MCS. On the day of fMRI experiment, 14 days after spinal cord lesion, the animals were anesthetized and epidural bipolar platinum electrodes were placed above the left primary motor cortex. Two 10-min sessions of fMRI were performed before and after a session of MCS (50 μA, 50 Hz, 300 μs, for 30 min). During each fMRI session, the right hindpaw was electrically stimulated (noxious stimulation: 5 mA, 5 Hz, 3 ms) using a block design of 20 s stimulation off and 20 s stimulation on. A general linear model-based statistical parametric analysis was used to analyze whole brain activation maps. Region of interest (ROI) analysis and paired t-test were used to compare changes in activation before and after MCS in these ROI.


RESULTS
MCS suppressed evoked blood oxygen dependent signals significantly (Family-wise error corrected P < 0.05) and bilaterally in 2 areas heavily implicated in nociceptive processing. These areas consisted of the primary somatosensory cortex and the prefrontal cortex.


CONCLUSIONS
These findings suggest that, in animals with SCL, MCS attenuates hypersensitivity by suppressing activity in the primary somatosensory cortex and prefrontal cortex.
Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland School of Dentistry, Baltimore, MD 21201, USA; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Li
L
Jiang
Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
Yadong
Y
Ji
Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland School of Dentistry, Baltimore, MD 21201, USA; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Pamela J
PJ
Voulalas
Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201, USA; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Michael
M
Keaser
Department of Sciences of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Core for Translational Research in Imaging at Maryland (C-TRIM), University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Su
S
Xu
Department of Sciences of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Core for Translational Research in Imaging at Maryland (C-TRIM), University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Rao P
RP
Gullapalli
Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201, USA; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Joel
J
Greenspan
Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland School of Dentistry, Baltimore, MD 21201, USA; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: Radi.masri@gmail.com.
Radi
R
Masri
D000818:Animals; D001931:Brain Mapping; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy / Q000379:methods*; D005260:Female; D005528:Foot; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D009044:Motor Cortex / Q000503:physiopathology*; D009437:Neuralgia / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D017397:Prefrontal Cortex / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000503:physiopathology*
Central pain; Functional magnetic resonance imaging (fMRI); Motor cortex stimulation; Neuropathic pain; Noxious electrical stimulation