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.