Interaction of Intrathecally Infused Morphine and Lidocaine in Rats (Part II): Effects on the Development of Tolerance to Morphine

Background: There has been little information regarding the effects of local anesthetics on tolerance to opioids, although chronic use of combination of opioids and local anesthetics is popular for pain control. This study was designed to examine the effects of lidocaine on morphine tolerance to somatic and visceral antinociception.

Methods: Rats received a continuous intrathecal infusion of morphine (0.3-10 micro sign]g middle dot] kg-1 middle dot] h-1), lidocaine (30-1000 micro sign]g middle dot] kg-1 middle dot] h-1), a combination of those, or saline. After 6- day infusion, intrathecal morphine challenge test (5 micro sign]g/10 micro sign]l) was performed, and time-response curve was constructed to assess the magnitude of tolerance. The tail flick (TF) test and colorectal distension (CD) test were used to measure somatic and visceral antinociceptive effects, respectively.

Results: Antinociceptive effects in the TF and CD tests caused by morphine challenge were reduced (P < 0.01) in the morphine infused groups. The magnitude of the tolerance was inversely associated with the amount of morphine infused. Lidocaine infusion induced no different change in the morphine challenge test from that seen in the saline infusion group. Development of tolerance was greater in morphine 3 micro sign]g middle dot] kg-1 middle dot] h-1 than in morphine 0.75 micro sign]g middle dot] kg-1 middle dot] h-1 + lidocaine 150 micro sign]g middle dot] kg-1 middle dot] h-1 despite their similar antinociceptive effects during intrathecal infusion. The infusion of a low dose of morphine (0.3 micro sign]g middle dot] kg-1 middle dot] h-1) did not reduce the antinociceptive effects in the challenge test.