Mechanisms underlying alterations in somatosensation and excercise induced pain following ischemic injury

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Ischemic injury leads to changes in somatosensory perception and enhanced exercise-induced pain. After ischemia-reperfusion injury in the hind paw, rats exhibit lowered paw-withdrawal thresholds to mechanical stimulation, behaviours suggesting that exercise is painful, and they exhibit even lower paw-withdrawal thresholds after exercise. To address the mechanisms underlying these alterations, we will compare the effects of exercise in naïve rats and rats with a hind paw IR injury on: 1) hind paw muscle thermoregulatory and nutritive blood flow using laser Doppler flowmetry and measures of tissue oxygen partial pressure; 2) hind paw muscle capillary no-reflow and muscle injury using India ink perfusion and a measure of mitochondrial oxidative capacity; 3) hind paw muscle lactate production and tissue acidosis using colorometric assays and assessment of tissue pH; 4) the antinociceptive effects of non-selective and selective ASIC antagonists in rats with ischemia-reperfusion injury.