Analgesia and tolerance to intrathecal morphine and norepinephrine infusion via implanted mini-osmotic pumps in the rat

Abstract

The duration of analgesia and the development of tolerance following continuous intrathecal administration of morphine and norepinephrine alone, and morphine followed by norepinephrine via mini-osmotic pumps were investigated in the rat. Analgesia was assessed by the tail-flick test. In single pump experiments morphine 1 .mu.1 (10 .mu.g)/h (7 days) and 0.5 .mu.l (10 .mu.g)/h (14 days) produced analgesia with tolerance by days 5-7. Norepinephrine 1 .mu.l (15 .mu.g)/h (7 days) produced analgesia equivalent to that of morphine with tolerance developing by day 3. Following continuous intrathecal morphine 1 .mu.l (10 .mu.g)/h for 5 days, norepinephrine 1 .mu.l (15 .mu.g)/h for 7 days failed to produce a significant increase in analgesia. This was in contrast to the increase in analgesia seen when the norepinephrine infusion followed a saline infusion. Determination of the norepinephrine concentration in the solution from the osmotic pumps verified that the norepinephrine is stable for the treatment period.