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Morphine tolerance increases [ 3 H]MK‐801 binding affinity and constitutive neuronal nitric oxide synthase expression in rat spinal cord. (National Medical Defense Center, Taipei, Taiwan) Br J Anaesth 2000;85:587–591.
Author(s) -
Wong ChihShung,
Hsu MingMan,
Chou YenYen,
Tao PaoLuh,
Tung CheSe
Publication year - 2001
Publication title -
pain practice
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 58
eISSN - 1533-2500
pISSN - 1530-7085
DOI - 10.1046/j.1533-2500.2001.01023-11.x
Subject(s) - nmda receptor , nitric oxide synthase , morphine , spinal cord , pharmacology , nitric oxide , medicine , receptor , dizocilpine , anesthesia , chemistry , psychiatry
N ‐Methyl‐D‐aspartate (NMDA) receptor antagonists and nitric oxide synthase (NOS) inhibitors inhibit morphine tolerance. In the present study, a lumbar subarachnoid polyethylene (PE10) catheter was implanted for drug administration to study alterations in NMDA receptor activity and NOS protein expression in a morphine‐tolerant rat spinal model. Antinociceptive tolerance induced by intrathecal morphine infusion (10 μg h −1 ) for 5 days. Co‐administered MK801 with morphine was used to inhibit the development of morphine tolerance. Lumbar spinal cord segments were removed and prepared for [ 3 H]MK‐801 binding assays and NOS western blotting. The binding affinity of [ 3 H]MK‐801 was higher in spinal cords of morphine‐related rats than in control rats. There was no difference in B max . Western blot analysis showed that constitutive expression of neuronal NOS protein in the morphine‐tolerant group was twice that in the control group. This up‐regulation was partially prevented by MK‐801. The results suggest that morphine tolerance affects NMDA receptor binding activity and increases nNOS expression in the rat spinal cord. Comment by Octavio Calvillo, M.D., Ph.D. Morphine tolerance may be due to receptor down‐regulation or receptor uncoupling; activation of the NMDA‐dependent pain‐facilitatory system may also play a role. It has been proposed that NMDA receptor activation may play a role in morphine tolerance. NMDA receptor antagonists and nitric oxide synthase [NOS] inhibitors may prevent morphine tolerance. Tolerance was induced in rats by intrathecal injection of morphine [10 ug /h] for 5 days, co‐administration of MK801 [NMDA antagonist] with morphine was used to prevent morphine tolerance. Lumbar spinal cord segments were removed and prepared for [H3]MK801 binding assays and NOS western blotting. The binding affinity of labeled MK801 was higher in spinal cords of morphine tolerant rats than in control rats. Western blot analysis showed that constitutive expression of neuronal NOS protein in the morphine tolerant rats was twice that in the control group, thus, up‐regulation was prevented by MK801. The results suggest that morphine tolerance affect NMDA receptor binding activity and increase neuronal protein expression in rat the spinal cord.