Nuclear factor kappaB signaling in opioid functions and receptor gene expression

Opiates are the most powerful of all known analgesics. The prototype opiate morphine has been used as a painkiller for several thousand years. Chronic usage of opiates not only causes drug tolerance, dependence, and addiction, but also suppresses immune functions and affects cell proliferation and cell survival. The diverse functions of opiates underscore the complexity of opioid receptor signaling. Several downstream signaling effector systems, including adenylyl cyclase, mitogen-activated protein kinase, Ca2+ channels, K+ channels, and phosphatidylinositol 3-kinase/Akt, have been identified to be critical in opioid functions. Nuclear factor-kappaB (NF-kappaB), one of the most diverse and critical transcription factors, is one of the downstream molecules that may either directly or indirectly transmit the receptor-mediated upstream signals to the nucleus, resulting in the regulation of the NF-kappaB-dependent genes, which are critical for the opioid-induced biological responses of neuronal and immune cells. In this minireview, we focus on current understanding of the involvement of NF-kappaB signaling in opioid functions and receptor gene expression in cells.