Chronic pain is alleviated in a mammal suffering there from by administering to the mammal a chronic pain alleviating amount of a nontoxic N-methyl-D-aspartate receptor antagonist such as dextromethorphan, dextrorphan, ketamine or pharmaceutically acceptable salt thereof, in combination with a .mu.-opiate analgesic such as tramadol or an analogously acting molecular entity, and a methylxanthine such as caffeine, and optionally in sustained release dosage form.