Small animal, whole brain fMRI: innocuous and nociceptive forepaw stimulation

Supra-spinal pain processing involves a number of extensive networks. An examination of these networks using small animal functional magnetic resonance imaging (fMRI) is difficult. While prior studies have successfully delineated regions consistent with known pain processing pathways, they have been restricted to acquisitions of limited spatial extent with coarse in-plane resolution to achieve a high temporal resolution. An isotropic, whole brain fMRI protocol has been developed for the examination of the supra-spinal consequences of innocuous and nociceptive electrical stimulation of the rat forepaw. Innocuous electrical stimulation of the rat forepaw delineated BOLD contrast responses consistent with known somatosensory processing pathways (contralateral primary somatosensory cortex (S1), a region consistent with secondary somatosensory cortex, the ventral posterolateral thalamic nucleus and ipsilateral cuneate nucleus), providing face validity for the technique. The putative noxious stimulus delineated additional regions consistent with the classical lateral and medial pain systems as well as secondarily associated areas: the aversion and descending inhibition systems. These included the ipsilateral inferior colliculus, anterior pretectal nucleus, mediodorsal thalamic nucleus, with regions in the pre-frontal, cingulated, ventral orbital and infra-limbic cortices, nucleus accumbens all exhibiting negative BOLD changes. Such regions are in agreement with, and extend, those previously reported. Acquisition, post-processing and analysis methodologies undertaken in this study constitute a marked extension of previous fMRI in the rat, enabling whole brain coverage at a spatial resolution sufficient to delineate regional changes in BOLD contrast consistent with somatosensory and nociceptive networks.