Proteomic analysis of spinal protein expression in rats exposed to repeated intrathecal morphine injection.
Repeated administration of morphine for treating severe chronic pain may lead to neuroadaptive changes in the spinal cord that are thought to underlie molecular mechanisms of the development of morphine tolerance and physical dependence. Here, we employed a 2-D gel-based proteomic technique to detect the global changes of the spinal cord protein expression in rats that had developed morphine tolerance. Morphine tolerance at the spinal cord level was induced by repeated intrathecal injections of morphine (20 microg/10 microL) twice daily for 5 days and evaluated by measurements of paw withdrawal latencies and maximal possible analgesic effect at day 5. After behavioral tests, the lumbar enlargement segments of spinal cord were harvested and proteins resolved by 2-DE. We found that eight proteins were significantly up-regulated or down-regulated in spinal cord after morphine tolerance development, including proteins involved in targeting and trafficking of the glutamate receptors and opioid receptors, proteins involved in oxidative stress, and cytoskeletal proteins, some of which were confirmed by Western blot analysis. Morphine-induced expressional changes of these proteins in the spinal cord might be involved in the central mechanisms that underlie the development of morphine tolerance. It is very likely that these identified proteins may serve as potential molecular targets for prevention of the development of morphine tolerance and physical dependence.
Shui
Hao-Ai
HA
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Ho
Shung-Tai
ST
Wang
Jhi-Joung
JJ
Wu
Chin-Chen
CC
Lin
Chih-Huan
CH
Tao
Yuan-Xiang
YX
Liaw
Wen-Jinn
WJ
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance / Q000502:physiology*; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D020543:Proteome / Q000187:drug effects* / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D000701:Analgesics, Opioid; D020543:Proteome; D009020:Morphine