Abstract: The MAPKs activation pathway consists of three protein kinases in activation sequence: MAPKs kinase kinases (MKKKs) →MAPKs kinases (MKKs) →MAPKs and four pathways:extracellular signal-regulated kinase (MAPKERK), c-Jun N-terminal kinase (MAPKJNK), MAPKP38 and MKK5/MAPKERK5 activation pathways.It has been proved that MAPKs(ERK,JNK and P38) are acvtivated in the progress of morphine tolerance. Inhibitors of each and every element of MAPKs activation pathway are promising clinical drugs for morphine tolerance.

Key words: mitogen-activated proteins kinases, morphine tolerance, MAPKs inhibitiors