ABSTRACT
Pathological pain or clinical pain is caused by tissue and nerve injuries, and is usually chronic and mainly divided into inflammatory pain and neuropathic pain. Pathological pain is typically characterized by hyperalgesia (increased responsiveness to noxious stimuli) and allodynia (painful responses to normally innocuous stimuli). The mitogen-activated proteins kinases (MAPKs) are a family of evolutionally conserved molecules that play a critical role in cell signaling, consisting of extracellular signal regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK), which play an important role in neural plasticity of pathological pain. Inhibition of MAPKs alleviates inflammatory pain and neuropathic pain in different animal models. It is very important to study the inhibition of MAPKs as a therapeutic approach to treat pathological pain.
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 (MAPK~(ERK)),C-JUN N-terminal kinase (MAPK~(JNK)),MAPK~(P38) and MKKS/MAPK~(ERK5) activation pathways.It has been proved that MAPKs(ERK,JNK and P38) are acvtivated in the progress of morphine tolerance.Inhibitors of any element of MAPKs activation pathway may function as a potential clinical medicine for morphine tolerance.
