Time-dependent and dose-dependent effects of fenfluramine upon pain thresholds

Fenfluramine increases brain serotonin levels soon after injection, followed by chronic serotonin depletions 48–72 h thereafter. Because serotonin content has been implicated in both basal and analgesic nociceptive processes, the present study evaluated fenfluramine’s dose-dependent and time-dependent effects upon pain thresholds in rats as measured by three tests: flinch-jump, tail flick, and liminal escape. Fenfluramine increased all three nociceptive thresholds .5 h following injection. Important test-specific differences were observed, with antinociceptive responses following effective fenfluramine doses of 2.66 mg/kg on the flinch-jump test, 13.3 mg/ kg on the tail-flick test, and 26.6 mg/kg on the liminal escape test, with the last effect apparently due to overall behavioral disruption. In contrast, fenfluramine failed to alter pain thresholds 48 and 72 h after injection but significantly decreased tail-flick latencies 96 h following the lowest dose. Previous reports of morphological abnormalities following fenfluramine administration were not confirmed. While these data confirm previous reports that increases in serotonin levels produce antinociceptive effects, they do not support the contention that serotonin depletion results in hyperalgesia.