Reductions in pain thresholds and morphine analgesia following intracerebroventricular parachlorophenylalanine

The selective decreases in both basal and analgesic pain thresholds following systemic administration of parachlorophenylalanine (PCPA) has been attributed to the inhibition of tryptophan hydroxylase and subsequent depletion of brain serotonin. These effects only occur at high systemic doses which have other general debilitating effects. The present study examined the relationship between PCPA's nociceptive and serotonin-depleting effects following intracerebroventricular (ICV) administration. The first experiment determined that an ICV dose of 3 mg, but not 1 mg, of PCPA significantly decreased jump thresholds at 0.5, 48 and 120 hr after injection. These effects were not due to osmolarity shifts since hypertonic saline injections failed to alter thresholds. The second experiment demonstrated a time-dependent reduction of morphine (5 mg/kg) analgesia as a function of the interval between ICV PCPA and the systemic morphine injection. PCPA reduced morphine analgesia if it was administered 24 hr prior to the opiate and eliminated morphine analgesia if it was administered 48 hr prior to the opiate. Pretreatment with ICV PCPA either 0.5 or 72 hr prior to the opiate failed to alter morphine analgesia. The third and fourth experiments indicated that hippocampal and spinal levels of either serotonin or 5-hydroxyindoleacetic acid were not significantly affected by ICV PCPA pretreatment. These data indicate that the hyperalgesia and morphine analgesia impairments noted following ICV PCPA do not correspond with changes in serotonin from hippocampal or spinal tissue and such effects are discussed in terms of alternative modes of action.