Abstract

A chronic constriction trigeminal nerve injury model (CCI-ION) was utilized for comparisons to healthy naive male rats using manganese-enhanced magnetic resonance imaging. The CCI-ION model was induced by unilaterally placing 2 ties of chromic gut suture around the infraorbital nerve within the orbital cavity. Throughout the study, mechanical sensitivity was tested weekly on the whisker pad, the receptive field of the ION. In week 8 when hypersensitivity was chronic, anxiety-like behavior were assayed using the light-dark place preference and elevated plus maze tests. In week 10, animals were injected with 62mg/kg MgCl2 dissolved in saline 24hrs prior to the scan with a 7-Tesla MRI machine. Animals were anesthetized with 2-2.5% isoflurane, positioned within a small bore quadrature RF coil (inner diameter = 86mm), and a phase array surface coil employed for signal excitation and detection, respectively. Respiration and heart rate were monitored, and body temperature was maintained at 37.0 ± 0.5°C. T1-weighted images were acquired with a fast sequence producing signals (gradient echo) with low flip angles sequence (FLASH). Repetition Time (TR)/Echo Time (TE) = 500 ms/3ms, Field of View (FOV)=3.5cm × 3.5cm, slice thickness=0.5mm, inter-slice distance=0.5mm, number of slice =40, matrix=256 × 256, number of average=21. Within 3wks after CCI-ION model induction, reflexive mechanical hypersensitivity was maximal and persisted until experiment's end. Rats with the chronic pain model displayed anxiety-like behavior, spending significantly more time in the dark chamber and preferentially staying in the closed arm without looking into the open arms of the elevated plus maze. CCI-ION rats had increased MEMRI signals within the anterior cingulate cortex, amygdala, habenula, and thalamus, while signals in the periaqueductal grey, dentate gyrus, pyriform cortex, and ventral tegmental area were not different compared to naive rats. These studies will assist understanding of neuropathic chronic pain associated process and changes in the brain.

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