Capsaicin-sensitive mechanisms are involved in cortical spreading depression-associated cerebral blood flow changes...

We tested the hypothesis that capsaicin-sensitive mechanisms play a role in the cortical spreading depression (CSD)-related changes in cortical blood flow (CBF). CBF was measured with laser Doppler flowmetry in anesthetized rats. The animals were treated with capsaicin before (48 h-2 weeks) or during the experiments. This agent is thought to stimulate small-diameter sensory nerve fibers selectively and to deplete stored peptides. In the vehicle-treated group (n=8), the peak value of the CSD-associated hyperperfusion was 257+/-12% above the baseline (mean+/-SEM, P<0.05). In the groups treated with 20 and 40 microg/kg or 20 mg/kg capsaicin, there were only small decreases in CBF. In the groups treated with 100 mg/kg capsaicin, the CSD-associated hyperemia was reduced at 48 h (158+/-7%, P<0.05). However, at 96 h a transient hyperresponsiveness (390+/-38%, P<0.05) was observed, which had disappeared by 2 weeks. These results indicate that the manipulation of sensory neuropeptide stores results in a biphasic effect on CSD-induced CBF responses.