Neuroimaging of pain in animal models: a review of recent literature

Abstract

Neuroimaging of pain in animals allows us to better understand mechanisms of pain processing and modulation. In this review, we discuss recently published brain imaging studies in rats, mice, and monkeys, including functional magnetic resonance imaging (MRI), manganese-enhanced MRI, positron emission tomography, and electroencephalography. We provide an overview of innovations and limitations in neuroimaging techniques, as well as results of functional brain imaging studies of pain from January 1, 2016, to October 10, 2018. We then discuss how future investigations can address some bias and gaps in the field. Despite the limitations of neuroimaging techniques, the 28 studies reinforced that transition from acute to chronic pain entails considerable changes in brain function. Brain activations in acute pain were in areas more related to the sensory aspect of noxious stimulation, including primary somatosensory cortex, insula, cingulate cortex, thalamus, retrosplenial cortex, and periaqueductal gray. Pharmacological and nonpharmacological treatments modulated these brain regions in several pain models. On the other hand, in chronic pain models, brain activity was observed in regions commonly associated with emotion and motivation, including prefrontal cortex, anterior cingulate cortex, hippocampus, amygdala, basal ganglia, and nucleus accumbens. Neuroimaging of pain in animals holds great promise for advancing our knowledge of brain function and allowing us to expand human subject research. Additional research is needed to address effects of anesthesia, analysis approaches, sex bias and omission, and potential effects of development and aging.

Pain modulatory network is influenced by sex and age in a healthy state and during osteoarthritis progression in rats

“…The exposure to isoflurane during the scan was also shorter than standard in vivo techniques and did not require tracheal intubation. Resting‐state networks are generally preserved and highly reproducible between animals under low dose of isoflurane compared to alpha‐chloralose and awake fMRI protocol, which can significantly induce stress (Da Silva & Seminowicz, 2019; Low et al, 2016; Williams et al, 2010).…”

Preclinical Neuropathic Pain Assessment; the Importance of Translatability and Bidirectional Research

“…The use of PET and MRI for assessment of the brain response to pain, in man, particularly neuropathic pain have been reviewed previously ( Peyron et al, 2000 ; Moisset and Bouhassira, 2007 ; Morton et al, 2016 ). Their applicability within rodents positions their use as a key translational biomarker in understanding the same processes from the clinic to the pre-clinical situation ( Tracey and Mantyh, 2007 ; Thompson and Bushnell, 2012 ; Da Silva and Seminowicz, 2019 ; Tracey et al, 2019 ). In rodents, MRI is the most commonly used with PET rarely employed ( Da Silva and Seminowicz, 2019 ).…”

“…Their applicability within rodents positions their use as a key translational biomarker in understanding the same processes from the clinic to the pre-clinical situation ( Tracey and Mantyh, 2007 ; Thompson and Bushnell, 2012 ; Da Silva and Seminowicz, 2019 ; Tracey et al, 2019 ). In rodents, MRI is the most commonly used with PET rarely employed ( Da Silva and Seminowicz, 2019 ). MRI has the advantage of providing better spatial and temporal resolution than PET.…”

Psychotherapy in pain management: New viewpoints and treatment targets based on a brain theory

“…The salience network and DMN have been implicated in attention toward or away from pain. In relation to neuroimaging in animal models, chronic pain brain alterations are most commonly observed in regions associated with emotion and motivation, including PFC, ACC, hippocampus, amygdala, basal ganglia, and NAc [33] . The discussion will now shift to the columnar brain model.…”