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

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 mu g/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. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.