ABSTRACT
Objective To investigate the effects of curcumin (Cur) on activation of spinal Toll-like receptor 4 (TLR4) and on the chronic antinociceptive tolerance of morphine.Methods Sixty male Sprague-Dawley rats with successful intrathecal catheterization were randomly divided into four groups (n=15):saline (NS) group;morphine (MOR) group;curcumin (Cur) group and morphine plus curcumin (MOR+Cur) group.A morphine tolerance model of rats was induced by intrathecal ifjection of morphine 15μg,once a day for 7 consecutive days in MOR and MOR+Cur group;100μg curcumin was administered intrathecally once a day for 7 consecutive days in Cur and MOR+Cur group,10μl saline was administered intrathecally once a day for 7 consecutive days in NS group.The effect of curcumin intrathecal catheterization on morphine antinociceptive tolerance was explored by the tail flick latency (TFL) method and mechanical withdrawal threshold (MWT),and then the maximum possible potential effect (MPE) was calculated.The immunofluorescence staining method was applied to detect the effect of curcumin on the activation of lumbar spinal microglia.Real-time PCR and Western blotting were used to evaluate the effect of curcumin on the expression of mRNA and protein of spinal TLR4.Results The ％MPE TFL and ％MPE MWT increased significantly in MOR+Cur group than in MOR group (P＜0.05) after 7 days of intrathecal injection of morphine,intrathecal injection of curcumin and saline failed to induce analgesic effect.There was no significant difference in MPE between Cur group and NS group (P＞0.05).The lumbar spinal microglia increased markedly and the expressions of polyclonal antibody IBA-1 and TLR4 were significantly up-regulated in MOR group than in NS group (P＜0.05).The lumbar spinal microglia decreased obviously and the expressions of IBA-1 and TLR4 were significantly down-regulated in MOR+Cur group as compared with that in MOR group (P＜0.0S),but there was no significant difference in the expressions of IBA-1 and TLR4 between Cur group and NS group (P＞0.05).Conclusion Curcumin may attenuate chronic morphine antinociceptive tolerance through inhibiting spinal TLR4 up-regulation.