Effect of adrenalectomy on correlation of analgesia with tissue content of morphine

Adrenalectomy potentiated the antinociception of s.c. morphine (1.9-fold) but not that of i.c.v. morphine. After s.c. administration, the semilogarithmic plots of morphine content (plasma, brain, cerebrospinal fluid (CSF) or spinal cord) and morphine antinociception showed linearity for both sham-operated (SHAM) and adrenalectomized rats (ADX), and the regression lines for ADX showed leftward shifts (1.5-1.9-fold) compared with those for SHAM. After i.c.v. administration, the semilogarithmic plots of morphine content in brain or CSF and morphine antinociception showed linearity for both groups without difference in the regression lines for SHAM and for ADX, and the correlation between spinal morphine and antinociception was poor. Morphine was distributed in both brain and spinal cord after s.c., but was predominantly found in brain after i.c.v. administration. These results suggest that increased sensitivity to morphine is the main cause of adrenalectomy-induced potentiation of morphine antinociception and that adrenalectomy increases the sensitivity to morphine at the spinal site and/or potentiates the synergistic interaction of supraspinal and spinal morphine action.