1. Interaction between chronic and acute pain: down- regulation of motivational value for relief from acute pain 589 OHBM 2009 INTRODUCTION Our recent fMRI studies indicate that spontaneous pain of chronic back pain (CBP) engages brain regions distinct from that reported for thermal acute pain. Multiple earlier studies have examined brain activity for acute pain in various clinical conditions as a means of differentiating brain properties for chronic pain. Here we retest the latter notion when applied stimuli and reported perceptions are carefully matched, that is, what is the difference in brain processing of acute thermal between chronic pain patients and normal subjects. We used fMRI to examine brain activity associated with thermal pain perception in twelve CBP patients and matched healthy controls. METHODS 12 healthy subjects and CBP patients participated in this study and were trained to use the finger-span device to rate magnitude of their pain. In the scanner each volunteer performed thermal pain and one visual rating scan. The signals for pain and visual ratings were used to search for the BOLD signal using a GLM model (FSL software; fmrib, Smith et al. 2001). Group average maps for the 2 rating tasks, in addition to their contrast and conjunction are shown in panel 1. Percent BOLD change was extracted by computing deviation from the mean for voxels within the ROI and averaging the 9 stimulus repetitions for each trial type (Panel 2). Percent BOLD change from ROIs was correlated with acute and spontaneous pain (Panel 3). Functional networks were produced by extracting the BOLD time course from a seed region then computing correlation coefficient between the time course and the time courses from all other brain voxels (panel 4). Acute pain brain representation does not differ between Healthy and CBP, yet the motivational value of relief from acute pain seems to be discounted in chronic pain patients. Differential brain activity for acute pain between the 2 groups was localized to nucleus accumbens (NAc) and head of the caudate In both groups, NAc activity reflected acute pain salience by peaking at the stimulus onset, which preceded perception of pain In CBP we show a reversal of the signal at noxious stimulus offset, raising the possibility that in CBP subjects this stimulus interferes or disrupts CBP spontaneous pain. NAc in CBP exhibited stronger connectivity to frontal regions, which are involved in chronic pain perception. CONCLUSION Funded by NIH NINDS NS35115 M.N. Baliki 1 and A.V. Apkarian 1 1.Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 1 (b) Random-effects analysis for pain rating tasks in healthy and CBP. Many cortical areas were commonly activated including bilateral thalamus, insula, S2. The conjunction is shown in blue and represents voxels that were commonly activated for both groups. The contrast map shows regions differentially activated between groups and include bilateral head of the caudate and nucleus accumbens. (a) Top panel shows average pain ratings for painful heat in healthy (black trace) and CBP (gray trace), data presented as mean +/- S.E.M. Bottom panel shows the time course of the thermal stimulus applied to the lower back. Performance was the same in the two groups. Brain activity for thermal pain in healthy and CBP subjects R S2 (56 -26 18) Differences in NAc BOLD signal between CBP patients and healthy controls (a) Group-averaged NAc BOLD signals in healthy (blue) and CBP patients (red) are shown superimposed on the respective group-averaged pain ratings (grey area). The black trace represents the derivative of the stimulus time course. (b) Top panels show the average time course of the stimulus (black) and pain rating for healthy and CBP for window when the stimulation starts (left) and ends (right panel). The time courses were averaged across all stimulation epochs where subjects reported pain (> 5 on a scale of 0-100). Bottom Panels show the derivatives (d/dt, in absolute values) for pain ratings and the stimulus. (c) Top panel shows the NAc BOLD responses for in healthy and patients for the same time periods depicted in (b), lower panel show the individual mean BOLD response for the 2 peaks in CBP and healthy. (d) and (e) show the same data as in (b-c) for the time periods where the subject did not report any significant pain in response to the thermal stimulus (d), and where subjects rated the length of a visual bar in absence of painful stimulation (e). 2 5 Parametric correlates of NAC activity with acute and chronic pain (a) Average bold peaks for the time intervals shown in Panel 2. Both groups exhibited similar activity for the first peak. Healthy controls exhibit higher activity for peak 2, which showed inhibition in CBP. CBP exhibited higher baseline activity. (b) Activity at p2 was positively correlated with thermal pain ratings in healthy controls (left), and negatively in CBP (right). (c) The extent of activity of the NAc during baseline showed a strong positive correlation with individual VAS scores in CBP. 4 Functional intrinsic connectivity for NAC. (a) Group average connectivity maps (random effects, p<0.01) for all brain regions showing a significant correlation with The NAC activity. This network includes bilateral amygdala, caudate, putamen, medial thalamus, PAG, ventral striatum and ACC for both Healthy and CBP groups. However, the network is more extensive in CBP, and significantly stronger to the mPFC in CBP patients. (b) Scatter plot shows a strong correlation between the strength of NAc mPFC connectivity and VAS at the day of the scan.