Loss of intrathecal morphine analgesia in terminal cancer patients is associated with high levels of excitatory amino acids in the CSF.

Abstract

To examine excitatory amino acid (EAA) levels in the cerebrospinal fluid (CSF) of patients on long-term morphine treatment for terminal cancer pain relief and to correlate these with morphine's analgesic effect. Fourteen terminal cancer patients suffering severe pain and requiring long-term opioid treatment for pain relief were included. An intrathecal (IT) catheter was implanted at the L(3-4)/L(4-5) level and advanced 10 cm in a cephalad direction. IT morphine injection was started at 100 microgram q 12 hr with a daily incremental dose of 50 microgram until the effective dose was reached. The CSF was sampled (2 mL) as follows: 1) before the first IT morphine injection, 2) when the effective dose of morphine was reached, 3) when loss of morphine's analgesic effect at the effective dose (pain visual analogue scale > 5), and 4) after consecutive increases of the morphine dose (50 microgram, IT, daily) for satisfactory pain relief and up to double the effective dose. The concentrations of glutamate and aspartate in the CSF were determined. CSF levels of glutamate and aspartate at the effective dose of morphine were lower than the baseline levels and increased when pain intensity increased and when morphine's analgesic effect was lost. Long-term IT morphine administration was accompanied by an increase of EAA level in the CSF that was associated with a loss of morphine's analgesic effect.