Little is known about how long term occlusion of arterial blood flow to skeletal muscle affects the responses of thin fiber muscle afferents to static contraction. We are proposing to investigate the effects of femoral arterial occlusion on the responses of thin fiber afferents to static contraction of the triceps surae muscles in decerebrate rats. Femoral arterial occlusion will be induced for three periods of time, namely three minutes, 24 hours and 72 hours. The two latter periods are intended to simulate intermittent claudication in the humans, whereas the first is intended to serve as an indicator of short term arterial occlusion. In addition, the 24 and 72 hour periods will allow us to compare the effects of arterial occlusion on the responses of the afferents to contraction when there has been an increase in TRPVi receptors and presumably when there has not been an increase in these receptors (i.e., three minutes). There is substantial evidence that femoral arterial occlusion in rats simulates arterial blood flow to muscle in humans with intermittent claudication during both during rest and during exercise. We will pay particular attention to how arterial occlusion over time alters the responses of thin fiber afferents to static contraction. We will attempt to block pharmacologically the receptors on thin fiber muscle afferents to determine which ones are playing a functional role in causing the altered (and usually increased) responsiveness of the thin fiber afferents to contraction. These receptors include TRPVi, acid sensing ion channels (ASIC), and purinergic 2 receptors In addition we will attempt to determine the effect of tempol, and agent which reduces oxidative stress, on the thin fiber afferents responses to static contraction.
When blood flow to the leg is blocked by fatty plaques, people experience painful sensations when attempting to exercise. The experiments proposed in this research unit will attempt to characterize the specific chemicals that evoke this sensation of pain during exercise. The information obtained from these proposed studies may allow the development of drugs that prevent these exercise-induced painful sensations.
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