Resting-State Functional Connectivity and fMRI Activation Responses to Noxious Heat in Rat Spinal Cord

Abstract

The neural mechanisms involved in pain processing in the lumbar spinal cord are complex, but understanding these mechanisms is crucial for managing and interpreting the pathological processes of neuropathic pain. Functional MRI (fMRI) is a valuable non-invasive imaging tool that can evaluate and monitor the pain processing circuits in the lumbar spinal cord. This study aims to demonstrate that high resolution fMRI can delineate (1) nociceptive heat processing circuit with stimulus-driven fMRI, and (2) intrinsic lumbar functional circuit with resting state fMRI. We acquired high resolution resting state fMRI and heat-stimulus driven fMRI data from lumbar spinal cord in 9 anaesthetized rats on a 9.4T MRI scanner. FMRI activation patterns were derived along with resting state functional connectivity (rsFC) measures between spinal gray matter horns, within and across segments T12-L2. Our results revealed that robust inter-horn rsFC in rat lumbar spinal cord was detectable at 9.4T. In addition, the deep layers of the dorsal horn were activated across the thoracic and lumbar spinal cord when the rat’s hind-paw was stimulated with noxious heat. The rsFC and activation patterns varied between low thoracic and lumbar levels, demonstrating that the organization of pain processing circuits varies between the thoracic and lumbar levels. This work deepens our understanding of normal pain processing in the spine and confirms that fMRI may be used for future research in rats following neuropathic pain after spinal cord injuries and spinal cord stimulation.