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.
Highlights
Stimuli to pain-receptive areas of the brain[9]
On fMRI scans, the activated areas were clearly separated from each other, with the lateral side of the S1 region activated by forepaw stimulation and the medial side activated by hindpaw stimulation (Fig. 1A)
We developed an objective measure of allodynia using fMRI and an independent mouse model of neuropathic pain
Summary
Stimuli to pain-receptive areas of the brain[9] Another factor that influences the evaluation of neuropathic pain in behavioral analyses is observer bias. Previous studies have used intensity-based stimuli to investigate neuropathic pain in rodents, but these have not focused on the properties of peripheral nerve fibers[10,11]. To consider the properties of these different fiber types, peripheral fibers (Aβ-, Aδ-, C-fibers) were selectively stimulated to clarify their location of brain function, which enabled us to examine neuropathic pain in detail. Aβ-fibers must be selectively activated using a 2000 Hz stimulus of less than 2.2 mA2,12. With the use of rs-fc MRI, we evaluated the properties of brain networks in activation areas during task fMRI
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