Role of spinal colony-stimulating factor 1 in rats in morphine tolerance to analgesia

ObjectiveTo investigate the role of spinal colony-stimulating factor 1(CSF1) in morphine tolerance to analgesia.

MethodsMale Sprague-Dawley rats with successful intrathecal catheter were randomly divided into four groups(n=15): 0.9% sodium chloride solution group(NS), morphine group(MOR), CSF1R inhibitor PLX3397 group(PLX3397) and morphine plus PLX3397 group(MOR+ PLX3397).A morphine tolerance model of rats was induced by intrathecal injection of 15 μg morphine once daily for 7 consecutive days in MOR and MOR+PLX3397 group.PLX3397 was administered intragastrically in PLX3397 and MOR+PLX3397 group, 0.9% sodium chloride solution was administered intrathecally in NS and PLX3397 group.The role of CSF1 on morphine antinociceptive tolerance was explored by %MPE^TFL and %MPE^MWT.Immunohistochemistry assay was applied to detect the expression of IBA-1.Western blotting was used to evaluate the change of spinal CSF1 expression.

ResultsIntrathecal injection of morphine for 7 days, %MPE in MOR group showed progressive decrease, while %MPE in MOR+PLX3397 group were significantly increased as compared with MOR group on day 3, 5, 7 after chronic morphine(P < 0.05);There was no significant difference in %MPE between PLX3397 and NS group(P>0.05).on day 7 after chronic morphine, the expression of IBA-1 in MOR group was significantly up-regulated as compared with NS group(P < 0.05), while the expression of IBA-1 in MOR+PLX3397 group was significantly down-regulated as compared with MOR group(P < 0.05);the expression of CSF1 in MOR and MOR+PLX3397 group was significantly up-regulated as compared with NS group(P < 0.05).

ConclusionsCSF1 in the spinal cord can be involved in the development of tolerance to morphine-induced analgesia.Inhibition of CSF1 may provide a new therapeutic target for morphine tolerance to analgesia.