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Beyond patient reported pain: perfusion magnetic resonance imaging demonstrates reproducible cerebral representation of ongoing post-surgical pain.

Howard MA, Krause K, Khawaja N, Massat N, Zelaya F, Schumann G, Huggins JP, Vennart W, Williams SC, Renton TF - PLoS ONE (2011)

Bottom Line: Here we used pulsed-continuous arterial spin-labelling [pCASL], a relatively novel perfusion magnetic-resonance imaging technique, in conjunction with a commonly-used post-surgical model, to measure changes in regional cerebral blood flow [rCBF] associated with the experience of being in ongoing pain.Regions of rCBF increases are plausibly associated with pain and the technique is reproducible, providing an attractive proposition for testing interventions for on-going pain that do not rely solely on patient self-report.Our findings have the potential to improve our understanding of the cerebral representation of persistent painful conditions, leading to improved identification of specific patient sub-types and implementation of mechanism-based treatments.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroimaging, Institute of Psychiatry, Kings College London, London, United Kingdom. Matthew.Howard@kcl.ac.uk

ABSTRACT
Development of treatments for acute and chronic pain conditions remains a challenge, with an unmet need for improved sensitivity and reproducibility in measuring pain in patients. Here we used pulsed-continuous arterial spin-labelling [pCASL], a relatively novel perfusion magnetic-resonance imaging technique, in conjunction with a commonly-used post-surgical model, to measure changes in regional cerebral blood flow [rCBF] associated with the experience of being in ongoing pain. We demonstrate repeatable, reproducible assessment of ongoing pain that is independent of patient self-report. In a cross-over trial design, 16 participants requiring bilateral removal of lower-jaw third molars underwent pain-free pre-surgical pCASL scans. Following extraction of either left or right tooth, repeat scans were acquired during post-operative ongoing pain. When pain-free following surgical recovery, the pre/post-surgical scanning procedure was repeated for the remaining tooth. Voxelwise statistical comparison of pre and post-surgical scans was performed to reveal rCBF changes representing ongoing pain. In addition, rCBF values in predefined pain and control brain regions were obtained. rCBF increases (5-10%) representing post-surgical ongoing pain were identified bilaterally in a network including primary and secondary somatosensory, insula and cingulate cortices, thalamus, amygdala, hippocampus, midbrain and brainstem (including trigeminal ganglion and principal-sensory nucleus), but not in a control region in visual cortex. rCBF changes were reproducible, with no rCBF differences identified across scans within-session or between post-surgical pain sessions. This is the first report of the cerebral representation of ongoing post-surgical pain without the need for exogenous tracers. Regions of rCBF increases are plausibly associated with pain and the technique is reproducible, providing an attractive proposition for testing interventions for on-going pain that do not rely solely on patient self-report. Our findings have the potential to improve our understanding of the cerebral representation of persistent painful conditions, leading to improved identification of specific patient sub-types and implementation of mechanism-based treatments.

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(a–f) Time courses of post-surgical rCBF increases relating to pain in each a priori-defined ROI.Cluster-corrected (p<0.05) Z-statistic map (red) indicates regional post-surgical increases in CBF relating to pain. In each row, a priori ROI masks are outlined in yellow. Plots at far right of each row indicate time courses of post-surgical increases in CBF (ml/100 g/min) for each ROI extracted from each individual pCASL scan (Red  =  left hemisphere, Blue  =  right hemisphere; Error bars represent ±1 Standard Error).
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pone-0017096-g003: (a–f) Time courses of post-surgical rCBF increases relating to pain in each a priori-defined ROI.Cluster-corrected (p<0.05) Z-statistic map (red) indicates regional post-surgical increases in CBF relating to pain. In each row, a priori ROI masks are outlined in yellow. Plots at far right of each row indicate time courses of post-surgical increases in CBF (ml/100 g/min) for each ROI extracted from each individual pCASL scan (Red  =  left hemisphere, Blue  =  right hemisphere; Error bars represent ±1 Standard Error).

Mentions: A distributed network of brain regions demonstrated significant increases in rCBF relating to pain following extraction of left and right third molars, compared to pain-free pre-surgical periods in the same subjects. Table 1 details each cluster in brain regions we hypothesised a priori would demonstrate CBF changes during post-surgical pain; for brevity, only clusters with highest Z-scores per anatomical region have been reported. We did not observe any post-surgical decreases in CBF in these regions or elsewhere. In particular, bilateral increases in rCBF during post-surgical pain were identified in postcentral gyrus, specifically the somatotopic region of S1 relating to the face/jaw[48], [49] (Figure 2; 3a), in SII (Figure 3b), extending ventrally towards posterior insula cortex and in mid/anterior insula cortices, extending towards the frontal operculum. At midline, clusters were observed bilaterally in mid-anterior cingulate cortices, (Figure 3c) extending towards perigenual cingulate cortex, and in posterior cingulate gyrus close to the splenium of the corpus callosum. In the temporal lobe, clusters were identified in amygdala (Figure 3d), extending dorsally through hippocampal/parahippocampal cortices (Figure 3e). In the thalamus, a single, bilateral interconnected cluster was identified which included pulvinar, ventral posterior, ventromedial and anterior regions at midline, extending inferiorly to include the hypothalamus (Figure 3f).


Beyond patient reported pain: perfusion magnetic resonance imaging demonstrates reproducible cerebral representation of ongoing post-surgical pain.

Howard MA, Krause K, Khawaja N, Massat N, Zelaya F, Schumann G, Huggins JP, Vennart W, Williams SC, Renton TF - PLoS ONE (2011)

(a–f) Time courses of post-surgical rCBF increases relating to pain in each a priori-defined ROI.Cluster-corrected (p<0.05) Z-statistic map (red) indicates regional post-surgical increases in CBF relating to pain. In each row, a priori ROI masks are outlined in yellow. Plots at far right of each row indicate time courses of post-surgical increases in CBF (ml/100 g/min) for each ROI extracted from each individual pCASL scan (Red  =  left hemisphere, Blue  =  right hemisphere; Error bars represent ±1 Standard Error).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3044150&req=5

pone-0017096-g003: (a–f) Time courses of post-surgical rCBF increases relating to pain in each a priori-defined ROI.Cluster-corrected (p<0.05) Z-statistic map (red) indicates regional post-surgical increases in CBF relating to pain. In each row, a priori ROI masks are outlined in yellow. Plots at far right of each row indicate time courses of post-surgical increases in CBF (ml/100 g/min) for each ROI extracted from each individual pCASL scan (Red  =  left hemisphere, Blue  =  right hemisphere; Error bars represent ±1 Standard Error).
Mentions: A distributed network of brain regions demonstrated significant increases in rCBF relating to pain following extraction of left and right third molars, compared to pain-free pre-surgical periods in the same subjects. Table 1 details each cluster in brain regions we hypothesised a priori would demonstrate CBF changes during post-surgical pain; for brevity, only clusters with highest Z-scores per anatomical region have been reported. We did not observe any post-surgical decreases in CBF in these regions or elsewhere. In particular, bilateral increases in rCBF during post-surgical pain were identified in postcentral gyrus, specifically the somatotopic region of S1 relating to the face/jaw[48], [49] (Figure 2; 3a), in SII (Figure 3b), extending ventrally towards posterior insula cortex and in mid/anterior insula cortices, extending towards the frontal operculum. At midline, clusters were observed bilaterally in mid-anterior cingulate cortices, (Figure 3c) extending towards perigenual cingulate cortex, and in posterior cingulate gyrus close to the splenium of the corpus callosum. In the temporal lobe, clusters were identified in amygdala (Figure 3d), extending dorsally through hippocampal/parahippocampal cortices (Figure 3e). In the thalamus, a single, bilateral interconnected cluster was identified which included pulvinar, ventral posterior, ventromedial and anterior regions at midline, extending inferiorly to include the hypothalamus (Figure 3f).

Bottom Line: Here we used pulsed-continuous arterial spin-labelling [pCASL], a relatively novel perfusion magnetic-resonance imaging technique, in conjunction with a commonly-used post-surgical model, to measure changes in regional cerebral blood flow [rCBF] associated with the experience of being in ongoing pain.Regions of rCBF increases are plausibly associated with pain and the technique is reproducible, providing an attractive proposition for testing interventions for on-going pain that do not rely solely on patient self-report.Our findings have the potential to improve our understanding of the cerebral representation of persistent painful conditions, leading to improved identification of specific patient sub-types and implementation of mechanism-based treatments.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroimaging, Institute of Psychiatry, Kings College London, London, United Kingdom. Matthew.Howard@kcl.ac.uk

ABSTRACT
Development of treatments for acute and chronic pain conditions remains a challenge, with an unmet need for improved sensitivity and reproducibility in measuring pain in patients. Here we used pulsed-continuous arterial spin-labelling [pCASL], a relatively novel perfusion magnetic-resonance imaging technique, in conjunction with a commonly-used post-surgical model, to measure changes in regional cerebral blood flow [rCBF] associated with the experience of being in ongoing pain. We demonstrate repeatable, reproducible assessment of ongoing pain that is independent of patient self-report. In a cross-over trial design, 16 participants requiring bilateral removal of lower-jaw third molars underwent pain-free pre-surgical pCASL scans. Following extraction of either left or right tooth, repeat scans were acquired during post-operative ongoing pain. When pain-free following surgical recovery, the pre/post-surgical scanning procedure was repeated for the remaining tooth. Voxelwise statistical comparison of pre and post-surgical scans was performed to reveal rCBF changes representing ongoing pain. In addition, rCBF values in predefined pain and control brain regions were obtained. rCBF increases (5-10%) representing post-surgical ongoing pain were identified bilaterally in a network including primary and secondary somatosensory, insula and cingulate cortices, thalamus, amygdala, hippocampus, midbrain and brainstem (including trigeminal ganglion and principal-sensory nucleus), but not in a control region in visual cortex. rCBF changes were reproducible, with no rCBF differences identified across scans within-session or between post-surgical pain sessions. This is the first report of the cerebral representation of ongoing post-surgical pain without the need for exogenous tracers. Regions of rCBF increases are plausibly associated with pain and the technique is reproducible, providing an attractive proposition for testing interventions for on-going pain that do not rely solely on patient self-report. Our findings have the potential to improve our understanding of the cerebral representation of persistent painful conditions, leading to improved identification of specific patient sub-types and implementation of mechanism-based treatments.

Show MeSH
Related in: MedlinePlus