A method of producing analgesia in a mammal is provided by rotational
(alternating) intrathecal administration to the mammal of a
pharmaceutically effective dose of at least one opioid receptor agonist,
such as a .mu.-, .delta.-, or .kappa.-opioid receptor agonist for a first
period of time, followed by intrathecal administration to the mammal of a
pharmaceutically effective dose of at least one opioid receptor-like
receptor 1 (ORL-1) agonist for a second period of time. The intrathecal
drug administration of the first and second periods of time may be
repeated a plurality of times without attaining tolerance in the mammal
to either drug. Implantable apparatus for rotational administration of
the active agents is also disclosed.