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.
Highlights
As many as 80% of individuals experience moderate to severe post-operative pain[1] and intractable pain in patients with cancer, diabetes and HIV is a major healthcare concern[2]
Reproducible rCBF increases that represent the experience of being in ongoing pain following third molar extraction (TME) including those in a network of brain regions specified a priori
Using pCASL, we have demonstrated reproducible, rCBFderived markers of ongoing, clinically-relevant pain
Summary
As many as 80% of individuals experience moderate to severe post-operative pain[1] and intractable pain in patients with cancer, diabetes and HIV is a major healthcare concern[2]. Standardised psychometric techniques have been developed, but inter-individual variability in pain reporting has often been incorrectly viewed as artefactual[4], rather than representing true differences in pain experience. It has been suggested that performance issues inherent in traditional analgesic development have been stymied by continuing to use the ‘‘evaluation tools and infrastructure of the last century to develop this century’s drug therapy’’[3]. With this in mind, novel indices for measuring pain are required; ideally they should relate to an underlying aspect of pain transduction, take account of bio-psycho-social factors and translate between human and preclinical studies[6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
