PMC

Data analysis. Shown are the statistical comparisons of different image acquisitions compared to baseline. A non-parametric Kruskal–Wallis test statistic was used to compare the average signal intensity in each of ca 15,000 voxel for their first 5 min baseline (acquisitions 1–50) to min 1–2 (acquisitions 51–71), min 3–5 (acquisitions 75–105), and min 8–10 (acquisitions 121–150) post-capsaicin and formalin.

BOLD signal change over time. Shown is the percent change in BOLD signal over a 10 min period (acquisitions 51–150) following capsaicin in wild-type controls (blue) and formalin injection in TRPV1 KO rats (red). The anterior cingulate cortex, a key area in the pain neural circuit, shows a maximal change in BOLD signal within 3–5 min post-injection of capsaicin or formalin. Trend lines (solid blue and red) represent simple moving averages over 25 timepoints. Vertical lines denote SEM.

Capsaicin-induced pain in wild-type rats. Shown on the left is a 3D color representation of the different brain areas comprising the putative pain neural circuit of the rat. The segmented, annotated illustration is a coronal view. The yellow/gold illustration below is confluence of the segmented brain areas showing the location of the average, significant increase (red) in BOLD signal for nine rats, 3–5 min after capsaicin injection into the right hind-foot. The panel of 2D axial images on the far left depict the location of significant increase in BOLD signal (red) in brain slices approximating the positions (A–E) shown in the 3D illustration.

Putative pain neural circuit. Shown is a 3D representation of the different volumes that comprise the putative pain neural circuit. The central image is a coronal view of a translucent shell of the brain showing the total composite and location of the different 3D volumes. Surrounding this are different layers of the neural circuit showing a ventral (deepest) to dorsal perspective of the different brain volumes. The panels on the top show the neural circuit in different orthogonal directions. The template used to define the neural circuit of pain in the rat was derived from the work of Gauriau and Bernard () and meta-analyses from various neuroimaging modalities used to study acute pain in humans (Apkarian et al., ).

Capsaicin pain in wild-type and TRPV1 rats. Shown are 3D color representations of the different brain areas comprising the putative pain neural circuit (top), Papez cortical loop (middle), and the habenular system (bottom) of the rat. The distinct areas comprising each neural circuit have been coalesced into a single 3D volume (shown in yellow), and are presented as a 3 × 3 grid in which rows correspond to each distinct neural circuit and columns correspond to experimental conditions. In the single 3D volume of each neural circuit, the red depicts the location of the average significant increase in BOLD signal 3–5 min after vehicle injection into wild-type Sprague-Dawley rats (left column), capsaicin injection into TRPV1-KO rats (middle column), and capsaicin injection into wild-type Sprague–Dawley rats (right column).

Lateralization of BOLD signal change over time. Shown below are activation maps of positive and negative BOLD signal following capsaicin injection into the right hindpaw of wild-type Sprague–Dawley rats (n = 9). The contralateral (left side) somatosensory cortex is circled in yellow for each time point. There is no clear lateralization of positive BOLD in the first 2 min of data acquisition. Instead there appears to be more negative BOLD as compared to the ipsilateral somatosensory cortex (right side). However, by 5 and 10 min post-capsaicin the contralateral side presents with more positive BOLD signal. Areas of activation have been smoothed. Colored BOLD activation scales indicate percent changes in positive BOLD (red spectrum) and negative BOLD (blue spectrum).