Skip to main content

Research Repository

Advanced Search

Manganese-enhanced magnetic resonance imaging depicts brain activity in models of acute and chronic pain: a new window to study experimental spontaneous pain?

Devonshire, Ian M.; Burston, James; Xu, Luting; Lillywhite, A.; Prior, M.J.; Watson, David J.G.; Greenspon, C.M.; Iwabuchi, Sarina J.; Auer, Dorothee P.; Chapman, Victoria

Authors

Ian M. Devonshire ian.devonshire@nottingham.ac.uk

James Burston james.burston@nottingham.ac.uk

Luting Xu

A. Lillywhite

M.J. Prior

David J.G. Watson

C.M. Greenspon charles.greenspon@nottingham.ac.uk

Sarina J. Iwabuchi

Dorothee P. Auer



Abstract

Application of functional imaging techniques to animal models is vital to understand pain mechanisms, but is often confounded by the need to limit movement artefacts with anaesthesia, and a focus on evoked responses rather than clinically relevant spontaneous pain and related hyperalgesia. The aim of the present study was to investigate the potential of manganese-enhanced magnetic resonance imaging (MEMRI) to measure neural responses during on-going pain that underpins hyperalgesia in pre-clinical models of nociception. As a proof of concept that MEMRI is sensitive to the neural activity of spontaneous, intermittent behaviour, we studied a separate positive control group undergoing a voluntary running wheel experiment.

In the pain models, pain behaviour (weight bearing asymmetry and hindpaw withdrawal thresholds (PWTs)) was measured at baseline and following either intra-articular injection of nerve growth factor (NGF, 10 µg/50 µl; acute pain model, n=4 rats per group), or the chondrocyte toxin monosodium iodoacetate (MIA, 1 mg/50 µl; chronic model, n=8 rats per group), or control injection. Separate groups of rats underwent a voluntary wheel running protocol (n=8 rats per group). Rats were administered with paramagnetic ion Mn2+ as soluble MnCl2 over seven days (subcutaneous osmotic pump) to allow cumulative activity-dependent neural accumulation in the models of pain, or over a period of running. T1-weighted MR imaging at 7 T was performed under isoflurane anaesthesia using a receive-only rat head coil in combination with a 72 mm volume coil for excitation.

The pain models resulted in weight bearing asymmetry (NGF: 20.0 ± 5.2%, MIA: 15 ± 3%), and a reduction in PWT in the MIA model (8.3 ± 1.5 g) on the final day of assessment before undergoing MR imaging. Voxel-wise and region-based analysis of MEMRI data did not identify group differences in T1 signal. However, MnCl2 accumulation in the VTA, right Ce amygdala, and left cingulate was negatively correlated with pain responses (greater differences in weight bearing), similarly MnCl2 accumulation was reduced in the VTA in line with hyperalgesia (lower PWTs), which suggests reduced regional activation as a result of the intensity and duration of pain experienced during the 7 days of MnCl2 exposure. Motor cortex T1-weighted signal increase was associated with the distance ran in the wheel running study, while no between group difference was seen. Our data suggest that on-going pain related signal changes identified using MEMRI offers a new window to study the neural underpinnings of spontaneous pain in rats.

Journal Article Type Article
Publication Date Aug 15, 2017
Journal NeuroImage
Print ISSN 1053-8119
Electronic ISSN 1095-9572
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 157
APA6 Citation Devonshire, I. M., Burston, J., Xu, L., Lillywhite, A., Prior, M., Watson, D. J., ā€¦Chapman, V. (2017). Manganese-enhanced magnetic resonance imaging depicts brain activity in models of acute and chronic pain: a new window to study experimental spontaneous pain?. NeuroImage, 157, https://doi.org/10.1016/j.neuroimage.2017.06.034
DOI https://doi.org/10.1016/j.neuroimage.2017.06.034
Keywords Nociception; fMRI; Manganese; On-going pain; Osteoarthritis
Publisher URL https://www.sciencedirect.com/science/article/pii/S1053811917305074?via%3Dihub
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0

Files

Devonshire et al_manganese enhanced magnetic resonance imaging.pdf (1.6 Mb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





You might also like



Downloadable Citations

;