Chronic generalized pain disrupts whole brain functional connectivity in mice.
Md Taufiq NasseefWeiya MaJai Puneet SinghNaoki DozonoKevin LançonPhilippe SéguélaEmmanuel DarcqHiroshi UedaBrigitte Lina KiefferPublished in: Brain imaging and behavior (2021)
Fibromyalgia (FM) is a generalized chronic pain condition whose pathophysiology is poorly understood, and both basic and translational research are needed to advance the field. Here we used the Sluka model to test whether FM-like pain in mice would produce detectable brain modifications using resting-state (rs) functional Magnetic Resonance Imaging (fMRI). Mice received intramuscular acid saline treatment, images were acquired at 7 T 5 days post-treatment, and pain thresholds tested 3 weeks post-scanning. Data-driven Independent Component Analysis revealed significant reduction of functional connectivity (FC) across several component pairs, with major changes for the Retrosplenial cortex (RSP) central to the default mode network, and to a lesser extent the Periaqueductal gray (PAG), a key pain processing area. Seed-to-seed analysis focused on 14 pain-related areas showed strongest FC reduction for RSP with several cortical areas (somatosensory, prefrontal and insular), and for PAG with both cortical (somatosensory) and subcortical (habenula, thalamus, parabrachial nucleus) areas. RSP-PAG FC was also reduced, and this decreased FC tended to be positively correlated with pain levels at individual subject level. Finally, seed-voxelwise analysis focused on PAG confirmed seed-to-seed findings and, also detected reduced PAG FC with the anterior cingulate cortex, increasingly studied in aversive pain effects. In conclusion, FM-like pain triggers FC alterations in the mouse, which are detected by rs-fMRI and are reminiscent of some human findings. The study reveals the causal fingerprint of FM-like pain in rodents, and indicates that both RSP and PAG connectional patterns could be suitable biomarkers, with mechanistic and translational value, for further investigations.
Keyphrases
- functional connectivity
- resting state
- chronic pain
- pain management
- neuropathic pain
- magnetic resonance imaging
- multiple sclerosis
- endothelial cells
- high resolution
- mass spectrometry
- high fat diet induced
- blood brain barrier
- spinal cord injury
- insulin resistance
- optical coherence tomography
- deep brain stimulation
- transcranial magnetic stimulation
- machine learning
- high frequency
- white matter
- convolutional neural network
- adipose tissue
- combination therapy
- transcranial direct current stimulation