A fMRI study of brain activations during non-noxious and noxious electrical stimulation of the sciatic nerve of rats

An acute pain animal model for fMRI study would provide useful spatial and temporal information for studying the supraspinal nociceptive neuronal responses. The aim of the present study was to investigate whether the nociceptive responses in different brain areas can be differentiated by using functional magnetic resonance imaging (fMRI) in anesthetized rats. Functional changes in brain regions activated by noxious or non-noxious stimuli of the sciatic nerve were investigated using fMRI in a 4.7 T MR system in alpha-chloralose anaesthetized rats. To determine the electrical intensity for noxious and non-noxious stimuli, compound action potential recording was employed to reveal the type of fibers activated by graded electrical stimulation of sciatic nerve. It showed that innocuous A-beta fibers were excited by two times the muscle twitch threshold and nociceptive A-delta and C fibers were recruited and excited by 10 and 20 times threshold, respectively. A series of four-slice gradient echo images were acquired during innocuous (two times threshold) and noxious (10 and 20 times threshold) stimuli in a 4.7 T MR system. Contralateral somatosensory cortex was the most prominent brain area activated by innocuous stimuli. Both signal intensity and activated areas were significantly increased in the somatosensory cortex, cingulate cortex, medial thalamus and hypothalamus during noxious stimuli. These four brain areas activated by noxious stimuli were significantly suppressed by prior intravenous injection of morphine (5 mg/kg). The present findings demonstrated that the difference of the innocuous and nociceptive responses in the brain could be detected and localized by an in vivo spatial map using fMRI. Results suggest that fMRI may be an invaluable tool for studying pain in anesthetized animals.