| Abstract: |
Interactions between the brain and the body are complex. The ability of the Pgp transport system to pump functionally active compounds from the brain to periphery defines a potentially important mechanism for the central nervous system to modulate peripheral systems. In Pgp1 antisense treated mice, lowering Pgp1 expression significantly enhanced systemic morphine analgesia and prevented tolerance, but diminished the analgesic activity of centrally administered morphine, implying that supraspinal analgesia resulted from a combination of central and peripheral mechanisms activated by morphine transported from the brain to the blood. Similarly, mice with a disruption of the Mdr1a gene were more sensitive to systemic morphine and less sensitive to morphine given centrally. Furthermore, in the mdr1a knockout mice, supraspinal morphine's peak effect occurred sooner than the wild-type mice, mirroring intrathecal morphine's peak effect time. These findings demonstrate Pgp1's role in the production of opioid analgesia. |
