Cardiovascular and neuromuscular issues in chronic pain

PROJECT SUMMARY / ABSTRACT Although chronic pain (CP) affects over 20% of the U.S. population, little is known about associated physiological consequences, which likely contribute to the patients’ functional limitations and high risk for cardiovascular disease. It is therefore the goal of this project to explore the impact of CP on cardiovascular

function and to evaluate the potential and underlying mechanisms of an innovative pain management strategy to improve circulatory control in this vulnerable patient group. Two disease-related characteristics predispose CP patients to cardiovascular abnormalities during exercise. First, an enhanced responsiveness of sensory

nerve endings and dorsal root ganglia (DRG) and the resulting high afferent feedback to medullary cardiovascular centers may exaggerate the exercise pressor reflex (EPR; a sympatho-excitatory reflex). Second, arterial baroreflex sensitivity (BRS), a sympatho-inhibitory reflex, may be decreased in CP. By studying both

patients with CP from lower limbs and well-matched controls, we will evaluate the impact of CP on these neurocirculatory control mechanisms and associated consequences for the hemodynamic and neuromuscular fatigue response to physical activities. We will use lumbar intrathecal fentanyl and both the Modified Oxford

method and the neck pressure/neck suction technique to evaluate the role of the EPR in determining the hemodynamic response to exercise and to determine baroreflex function. We will also study the impact of neuromodulation therapy (NMT), an innovative therapeutic approach that manages pain by electrically

stimulating the spinal cord or DRG and subsequently blocking sensory feedback from reaching the brain, on muscle sympathetic nerve activity (MSNA) and the hemodynamic and neuromuscular fatigue response to rest and exercise in patients with CP. We will use direct peroneal and radial nerve recordings to quantify MSNA

during handgrip and leg exercise. This will allow us to evaluate a) the direct effect of NMT (comparisons between NMT turned on vs turned-off) on efferent sympathetic nerve activity, and b) whether NMT affects EPR-mediated increases in sympathoexcitation during physical activity. Finally, ~40% of all CP patients suffer from clinical

hypertension. We will therefore conduct these studies in normotensive and hypertensive patients and determine the efficacy of NMT to normalize the well-known hemodynamic abnormalities, including exaggerated MSNA and BP, during exercise in hypertensive individuals. If this project can, as suggested by our preliminary data, confirm

a significant impact of CP on the circulatory and fatigue response to physical activity and that NMT can improve these impairments, but also the hemodynamic abnormalities associated with hypertension, the proposed studies will provide the scientific basis required to associate NMT with significant functional and cardiovascular health

benefits.