摘要 |
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.
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