Morphine tolerance and transcription factor expression in mouse spinal cord tissue.

Little is known about changes in gene expression responsible for the acquisition and maintenance of tolerance to the analgesic effects of opioids. In these studies we examine changes in the expression of several transcription factors in the spinal cords of morphine tolerant C57BL/6 mice. Western blots demonstrate a 1.9-fold increase in cyclic AMP response element binding protein (CREB) and a 2.4-fold increase phospho-CREB immunoreactivities in spinal cord homogenates from morphine tolerant animals. Likewise, Fos B and deltaFos B immunoreactivities were increased 2.2 and 2.3-fold, respectively. The expression of c-Fos remained unchanged. Immunohistological analysis showed the increase of phospho-CREB and Fos B/deltaFos B to be primarily in the dorsal horn region of the spinal cord. We conclude that chronic exposure to opioids causes changes in gene expression in sensory processing areas of the spinal cord.