Morphine is a classic
analgesic for the treatment of
chronic pain. However, its repeated use is known to produce tolerance, physical dependence, and addiction; these properties limit its long-term
therapeutic use and this has led to a quest for
therapeutics without these unwanted side effects. Understanding the molecular changes in response to long-term use of
morphine is likely to aid in the development of novel
therapeutics for the treatment of
pain. Studies examining the effects of chronic
morphine administration have reported alterations in gene expression, synapse morphology, and synaptic transmission implying changes in synaptic
protein profile. To fully understand the changes in
protein profiles, proteomic techniques have been used. Studies using two-dimensional gel electrophoresis of various brain regions combined with mass spectrometry have found alterations in the levels of a number of
proteins. However, neither the changes in brain regions relevant to
morphine effects nor changes in the abundance of synaptic
proteins have been clearly delineated. Recent studies employing subcellular fractionation to isolate the striatal synapse, combined with quantitative proteomics and graph theory-inspired network analyses, have begun to quantify
morphine-regulated changes in synaptic
proteins and facilitate the generation of networks that could serve as targets for the development of novel
therapeutics for the treatment of
chronic pain. Thus, an integrated quantitative proteomics and systems biology approach can be useful to identify novel targets for the treatment of
pain and other disorders of the brain.