Stabilization of morphine tolerance with long-term dosing: association with selective upregulation of mu-opioid receptor splice variant mRNAs.

ABSTRACT: Chronic morphine administration is associated with the development of tolerance, both clinically and in animal models. Many assume that tolerance is a continually progressive response to chronic opioid dosing. However, clinicians have long appreciated the ability to manage cancer pain in patients for months on stable opioid doses, implying that extended dosing may eventually result in a steady state in which the degree of tolerance remains constant despite the continued administration of a fixed morphine dose. Preclinical animal studies have used short-term paradigms, typically a week or less, whereas the clinical experience is based upon months of treatment. Chronic administration of different fixed morphine doses produced a progressive increase in the ED50 that peaked at 3 wk in mice, co

SUBMITTER: Xu J 

PROVIDER: S-EPMC4291645 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature