FDG PET Imaging of the Pain Matrix in Neuropathic Pain Model Rats

Abstract

Pain is an unpleasant subjective experience that is usually modified by complex multidimensional neuropsychological processes. Increasing numbers of neuroimaging studies in humans have characterized the hierarchical brain areas forming a pain matrix, which is involved in the different dimensions of pain components. Although mechanistic investigations have been performed extensively in rodents, the homologous brain regions involved in the multidimensional pain components have not been fully understood in the rodent brain. Herein, we successfully identified several brain regions activated in response to mechanical allodynia in neuropathic pain rat models using an alternative neuroimaging method based on 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG PET) scanning. Regions such as the medial prefrontal cortex, primary somatosensory cortex hindlimb region, and the centrolateral thalamic nucleus were identified. Moreover, brain activity in these regions was positively correlated with mechanical allodynia-related behavioral changes. These results suggest that FDG PET imaging in neuropathic pain model rats enables the evaluation of regional brain activity encoding the multidimensional pain aspect. It could thus be a fascinating tool to bridge the gap between preclinical and clinical investigations.

Imaging of pain using positron emission tomography

“…Increased tracer uptake in the lumbar spinal canal in the rat model of pain was observed. The elevated [ 51 Mn] Mn 2þ uptake can be observed after six days post-complete Freund's adjuvant, and the highest signal was found on day one post-injection [75].…”

“…Imaging data showed increased [ 18 F]FDG uptake in the medial prefrontal cortex, primary somatosensory cortex hindlimb region, and the centrolateral thalamic nucleus. The increased [ 18 F]FDG uptake was positively correlated with von Frey test data [51].…”

Radiotracers in the Diagnosis of Pain: A Mini Review

“…For example, research on neuropathic pain has demonstrated altered glucose metabolism in specific brain regions, such as the thalamus, insula, and anterior cingulate cortex, which are involved in pain perception and modulation. 27 Moreover, [18F]-FDG-PET has shown promise in identifying biomarkers for pain severity and treatment response in chronic pain patients, offering a potential means for personalized pain management. 28 A study by Biswal and colleagues evaluated [18F]-FDG imaging in six patients with chronic neuropathic pain in their lower extremities (four cases of complex regional pain syndrome, one case of chronic sciatica, and one case of neuropathic pain).…”

“…For example, research on neuropathic pain has demonstrated altered glucose metabolism in specific brain regions, such as the thalamus, insula, and anterior cingulate cortex, which are involved in pain perception and modulation. 27 Moreover, [18F]-FDG-PET has shown promise in identifying biomarkers for pain severity and treatment response in chronic pain patients, offering a potential means for personalized pain management. 28…”

Up-and-coming Radiotracers for Imaging Pain Generators

“…Recently, brain activity in regions such as the medial prefrontal cortex, primary somatosensory cortex hindlimb region, and the centrolateral thalamic nucleus were shown to be positively correlated with mechanical allodynia-related behavioral changes. 86 Behera et al used PET/MRI in a rat model to pinpoint increased 18F-FDG uptake in damaged nerves. The absorption of 18F-FDG and behavioral tests for allodynia in the afflicted paw were highly linked.…”