A role for the brainstem in central sensitisation in humans. Evidence from functional magnetic resonance imaging

Zambreanu, L., Wise, R. G., Brooks, J. C.W. ORCID: https://orcid.org/0000-0003-3335-6209, Iannetti, G. D. and Tracey, I. (2005) A role for the brainstem in central sensitisation in humans. Evidence from functional magnetic resonance imaging. Pain, 114 (3). pp. 397-407. ISSN 0304-3959

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Animal studies have established a role for the brainstem reticular formation, in particular the rostral ventromedial medulla (RVM), in the development and maintenance of central sensitisation and its clinical manifestation, secondary hyperalgesia. Similar evidence in humans is lacking, as neuroimaging studies have mainly focused on cortical changes. To fully characterise the supraspinal contributions to central sensitisation in humans, we used whole-brain functional magnetic resonance imaging at 3 T, to record brain responses to punctate mechanical stimulation in an area of secondary hyperalgesia. We used the heat/capsaicin sensitisation model to induce secondary hyperalgesia on the right lower leg in 12 healthy volunteers. A paired t-test was used to compare activation maps obtained during punctate stimulation of the secondary hyperalgesia area and those recorded during control punctate stimulation (same body site, untreated skin, separate session). The following areas showed significantly increased activation (Z>2.3, corrected P<0.01) during hyperalgesia: contralateral brainstem, cerebellum, bilateral thalamus, contralateral primary and secondary somatosensory cortices, bilateral posterior insula, anterior and posterior cingulate cortices, right middle frontal gyrus and right parietal association cortex. Brainstem activation was localised to two distinct areas of the midbrain reticular formation, in regions consistent with the location of nucleus cuneiformis (NCF) and rostral superior colliculi/periaqueductal gray (SC/PAG). The PAG and the NCF are the major sources of input to the RVM, and therefore in an ideal position to modulate its output. These results suggest that structures in the mesencephalic reticular formation, possibly the NCF and PAG, are involved in central sensitisation in humans.

Item Type: Article
Additional Information: Funding Information: We wish to acknowledge the Clarendon Fund and McDonnell-Pew Centre for Cognitive Neuroscience (LZ), the Wellcome Trust (RW), Dr Hardwen Trust (JCWB), the Medical Research Council UK (FMRIB Centre) and HEFCE (IT). We would also like to thank Dr Stephen Smith for image analysis advice and Prof. Anthony Dickenson for helpful advice and discussion.
Uncontrolled Keywords: brainstem,capsaicin,central sensitisation,fmri,hyperalgesia,neurology,clinical neurology,anesthesiology and pain medicine ,/dk/atira/pure/subjectarea/asjc/2800/2808
Faculty \ School: Faculty of Social Sciences > School of Psychology
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Depositing User: LivePure Connector
Date Deposited: 07 Sep 2022 12:31
Last Modified: 21 Oct 2022 01:36
URI: https://ueaeprints.uea.ac.uk/id/eprint/87821
DOI: 10.1016/j.pain.2005.01.005

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