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As described elsewhere in this review, it remains to be established whether these mechanistic insights can be used to develop opioid agonists or treatment paradigms that do not produce analgesic tolerance

Since the time course of the changes in ERK1/2 activity generally correlate with the development of morphine tolerance, it has been assumed (perhaps prematurely) that ERK1/2 activation plays a role in morphine tolerance

Analyses were anchored in ventricular CSF to capture central nervous system biology, with additional profiling of lumbar CSF and plasma to evaluate how these signals extend across biofluids

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Full results may take 12 months or longer, since peptides take time to work through cumulative cellular effects