Visualization of Brain Activity in a Neuropathic Pain Model Using Quantitative Activity-Dependent Manganese Magnetic Resonance Imaging

Abstract

Human brain imaging studies have revealed several regions that are activated in patients with chronic pain. In rodent brains, functional changes due to chronic pain have not been fully elucidated, as brain imaging techniques such as functional magnetic resonance imaging and positron emission tomography (PET) require the use of anesthesia to suppress movement. Consequently, conclusions derived from existing imaging studies in rodents may not accurately reflect brain activity under awake conditions. In this study, we used quantitative activation-induced manganese-enhanced magnetic resonance imaging to directly capture the previous brain activity of awake mice. We also observed and quantified the brain activity of the spared nerve injury (SNI) neuropathic pain model during awake conditions. SNI-operated mice exhibited a robust decrease of mechanical nociceptive threshold 14 days after nerve injury. Imaging on SNI-operated mice revealed increased neural activity in the limbic system and secondary somatosensory, sensory-motor, piriform, and insular cortex. We present the first study demonstrating a direct measurement of awake neural activity in a neuropathic pain mouse model.

Centralized nociplastic pain causing fibromyalgia: an emperor with no cloths?

“…In my opinion, this body of evidence demonstrate that fibromyalgia pain is real, but do not define the actual pain source. Similar increased neuronal activity in the brain pain processing areas is seen in humans and in animals with neuropathic pain [5,6].…”

Manganese Dynamics in Mouse Brain After Systemic MnCl2 Administration for Activation-Induced Manganese-Enhanced MRI

“…Whereas the cumulative dosage of the double administration is twice as much as that of the single administration, the differences in R1 values between the single and the double administration were small. When considering Mn 2+ toxicity, a single dose is more suitable for measuring changes in brain activity associated with brief stimuli or tasks using AIM-MRI, while repeated administration is suitable for capturing changes in persistent brain activity, such as in neurological disorders ( Kikuta et al, 2015 ), chronic pain ( Inami et al, 2019 ), and visualization of active polysynaptic circuits ( Almeida-Corrêa et al, 2018 ).…”

“…Acquisition and analysis methods for MRI data were similar to those previously described ( Kikuta et al, 2015 ; Inami et al, 2019 ). Mice were injected with MnCl 2 solutions (0.2 mmol kg –1 in saline, i.p.)…”

What Did We Learn About Fracture Pain from Animal Models?

“…However, some insights into possible reflection of pain states have recently been described for neuropathic pain imaging in awake animals and include enhanced neural activity in several brain regions. 121 …”