Functional magnetic resonance imaging of the human spinal cord and brainstem with application to pain states
Lead Research Organisation:
University of Oxford
Department Name: Clinical Neurosciences
Abstract
One in five people will experience chronic pain during their lives. Changes in the way the body processes pain signals are thought to underlie how, after injury, pain can become chronic.
When you hurt yourself, pain signals are carried from the damaged tissue to the brain. On their way to the brain, they pass up the spinal cord and through the brainstem. However, when trying to find out what goes wrong in chronic pain, current imaging methods only allow researchers to look within the brain and brainstem. We would like to develop new methods that would allow us to look within the spinal cord as well.
This is important for two reasons: (1) we know from animal experiments that the brainstem and spinal cord work together to increase or decrease the size of pain signals, and (2) abnormal changes in the function of the brainstem and spinal cord can make pain become chronic.
In this project we will see how pain signals are processed in the spinal cord and brainstem in humans, and by doing so, get a better understanding of how pain is controlled, and hopefully learn why some people develop chronic pain after injury.
When you hurt yourself, pain signals are carried from the damaged tissue to the brain. On their way to the brain, they pass up the spinal cord and through the brainstem. However, when trying to find out what goes wrong in chronic pain, current imaging methods only allow researchers to look within the brain and brainstem. We would like to develop new methods that would allow us to look within the spinal cord as well.
This is important for two reasons: (1) we know from animal experiments that the brainstem and spinal cord work together to increase or decrease the size of pain signals, and (2) abnormal changes in the function of the brainstem and spinal cord can make pain become chronic.
In this project we will see how pain signals are processed in the spinal cord and brainstem in humans, and by doing so, get a better understanding of how pain is controlled, and hopefully learn why some people develop chronic pain after injury.
Technical Summary
Background: Neuroimaging has revealed a network of brain regions thought to reflect how we perceive pain. However, nociceptive information relayed from peripheral nerves, is modulated at the spinal cord, brainstem and brain. Adjustment of signal transmission at each of these levels ultimately determines levels of brain activity observed. The spine‘s location makes it inaccessible to electrophysiological investigation, hence a non-invasive technique is needed. We propose to extend conventional blood oxygenation level dependent (BOLD) methods to the human spinal cord. Building on our recent research addressing physiological noise modelling in spinal images, we will expand this to the assessment of spinal cord function.
Aims/Objectives: (i) Verify existence of BOLD signal change in the spinal cord, using combination of: hypercapnic challenges and lateralised multi-modal stimulation; (ii) translate animal experiments demonstrating descending control of pain, to non-invasive studies in humans; (iii) investigate the effects of peripherally and centrally acting analgesic compounds in disrupting normal spinal - brainstem loops during painful stimulation; and (iv) determine brainstem and spinal predictors of secondary hyperalgesia, using the intradermal capsaicin model and novel connectivity analyses.
Methods/Design: In healthy subjects, using conventional BOLD sensitive imaging on a 3 tesla MR system: (i) examine the echo time (TE) dependence of signal changes in response to a hypercapnic challenge (CO2 breathing), and thereby determine the optimal TE for spinal FMRI. By delivering noxious (laser) and non-noxious (air-puff) stimuli to both sides of the body, we will record associated signal changes in the cord and brainstem. (ii) We will modulate pain-related activity within the spinal cord and brainstem, using either cognitively demanding tasks to distract subjects, or (iii) via centrally (remifentanil) or peripherally (lidocaine) acting analgesic compounds. Finally, (iv) we will inject capsaicin intradermally, and examine whether spinal and brainstem responses during punctate hyperalgesia are correlated, and examine whether they predict the presence and intensity of provoked symptoms.
Scientific & Medical relevance: At the level of the spinal cord, maladaptive responses to tissue injury (central sensitisation) may underlie the pathogenesis of chronic pain. Animal studies have revealed that modulation of nociceptive signal transmission occurs at all levels of the neuroaxis, and there is a pressing need for these data to be translated to humans, as well as provide a completely novel means of assessing spinal cord function (e.g. for assessing recovery following spinal cord injury, or for investigating the consequence of spinal plaques in multiple sclerosis on motor/sensory function).
Aims/Objectives: (i) Verify existence of BOLD signal change in the spinal cord, using combination of: hypercapnic challenges and lateralised multi-modal stimulation; (ii) translate animal experiments demonstrating descending control of pain, to non-invasive studies in humans; (iii) investigate the effects of peripherally and centrally acting analgesic compounds in disrupting normal spinal - brainstem loops during painful stimulation; and (iv) determine brainstem and spinal predictors of secondary hyperalgesia, using the intradermal capsaicin model and novel connectivity analyses.
Methods/Design: In healthy subjects, using conventional BOLD sensitive imaging on a 3 tesla MR system: (i) examine the echo time (TE) dependence of signal changes in response to a hypercapnic challenge (CO2 breathing), and thereby determine the optimal TE for spinal FMRI. By delivering noxious (laser) and non-noxious (air-puff) stimuli to both sides of the body, we will record associated signal changes in the cord and brainstem. (ii) We will modulate pain-related activity within the spinal cord and brainstem, using either cognitively demanding tasks to distract subjects, or (iii) via centrally (remifentanil) or peripherally (lidocaine) acting analgesic compounds. Finally, (iv) we will inject capsaicin intradermally, and examine whether spinal and brainstem responses during punctate hyperalgesia are correlated, and examine whether they predict the presence and intensity of provoked symptoms.
Scientific & Medical relevance: At the level of the spinal cord, maladaptive responses to tissue injury (central sensitisation) may underlie the pathogenesis of chronic pain. Animal studies have revealed that modulation of nociceptive signal transmission occurs at all levels of the neuroaxis, and there is a pressing need for these data to be translated to humans, as well as provide a completely novel means of assessing spinal cord function (e.g. for assessing recovery following spinal cord injury, or for investigating the consequence of spinal plaques in multiple sclerosis on motor/sensory function).