Functional brain mapping using specific sensory-circuit stimulation and a theoretical graph network analysis in mice with neuropathic allodynia

Abstract

Allodynia, a form of neuropathic pain, is defined as pain in response to a non-nociceptive stimulus. The brain regions responsible for pain, which are not normally activated, can be activated in allodynic mice by providing a suitable stimulus to Aβ-fibers, which transmit signals from tactile sensory fibers. Functional MRI (fMRI) can be used to objectively observe abnormal brain activation. In the present study, fMRI was conducted to investigate allodynia in mice; allodynia was generated by surgical injury at the L4 spinal nerve root, thus selectively stimulating sensory nerve fibers. In intact mice, only the primary somatosensory cortex (S1) was activated by stimulation of Aβ-fibers. Meanwhile, allodynic mice showed significantly higher BOLD signals in the anterior cingulate area (ACA) and thalamus. Using resting state fMRI, both degree and eigenvector centrality were significantly decreased in the contralateral S1, clustering coefficient and local efficiency were significantly increased in the ACA, and betweenness centrality was significantly higher in the ventral posterolateral nucleus of the thalamus. These results suggest that the observed abnormal BOLD activation is associated with defects in Aβ-fibers when Aβ-fibers in allodynic mice are selectively stimulated. The objective approach enabled by fMRI can improve our understanding of pathophysiological mechanisms and therapeutic efficacy.

Assessing cortical plasticity after spinal cord injury by using resting-state functional magnetic resonance imaging in awake adult mice

“…The animal respiration was monitored while the rs-fMRI was performed. The scan protocols used for the rs-fMRI have been previously described 25 . To construct a reference for the brain anatomy, high-resolution T 2 -weighted images (T 2 WIs) of the whole brain were acquired using a Rapid Acquisition with Relaxation Enhancement (RARE) method with the following parameters: effective time to echo (TE), 48 ms; time to repetition (TR), 6100 ms; RARE factor, 8; number of averages, 4; spatial resolution, 75 × 75 × 300 μm 3 ; and number of slices, 52.…”

“…A temporal bandpass filter was applied in the 0.009 Hz to 0.1 Hz range 27 . These data analysis methods were based on a previous article 25 . The functional connectivity among areas were analyzed using the regions defined in the Allen Brain Atlas 28 , 29 .…”

Differential effects of aquaporin-4 channel inhibition on BOLD fMRI and Diffusion fMRI responses in rat visual cortex

“…As previously described [25], SPM12 software (Welcome Trust Center for Neuroimaging, UK) and a tailor-made program (Matlab, The MathWorks, Inc., USA) were used for fMRI analysis. Image processing, consisting of slice timing correction, motion correction, normalization of brain coordinates, and smoothing (Gaussian kernel with FWHM of 0.6 mm), was performed for all fMRI data before statistical analysis.…”

The Application of Functional Magnetic Resonance Imaging in Neuropathic Pain

“…A similar phenomenon was also found in fMRI study of the SNI animal model by Komaki et al According to the physiological characteristics of each nerve fiber, the Aβ fiber can be selectively excited by a current of 2000 Hz, 2.2 mA. When the hind paws of normal rats were administered with 2000 Hz, 2.2 mA DC stimulation, it caused only significant activation of the S1 region; however, when the same intensity of current was used to stimulate the pain-sensing hypersensitivity zone of SNI rats, it was found that not only S1, ACC, and thalamus were also significant activated [45].…”