Inhibition of spinal astrocytic c-Jun N-terminal kinase (JNK) activation correlates with the analgesic effects of ketamine in neuropathic pain

Background: we have previously reported that inhibition of astrocytic activation contributes to the analgesic effects of intrathecal ketamine on spinal nerve ligation (snl)-induced neuropathic pain. however,the underlying mechanisms are still unclear. c-jun n-terminal kinase (jnk),a member of mitogen-activated protein kinase (mapk) family,has been reported to be critical for spinal astrocytic activation and neuropathic pain development after snl. ketamine can decrease lipopolysaccharide (lps)-induced phosphorylated jnk (pjnk) expression and could thus exert its anti-inflammatory effect. we hypothesized that inhibition of astrocytic jnk activation might be involved in the suppressive effect of ketamine on snl-induced spinal astrocytic activation.methods: immunofluorescence histochemical staining was used to detect snl-induced spinal pjnk expression and localization. the effects of ketamine on snl-induced mechanical allodynia were confirmed by behavioral testing. immunofluorescence histochemistry and western blot were used to quantify the snl-induced spinal pjnk expression after ketamine administration.results: the present study showed that snl induced ipsilateral pjnk up-regulation in astrocytes but not microglia or neurons within the spinal dorsal horn. intrathecal ketamine relieved snl-induced mechanical allodynia without interfering with motor performance. additionally,intrathecal administration of ketamine attenuated snl-induced spinal astrocytic jnk activation in a dose-dependent manner,but not jnk protein expression.conclusions: the present results suggest that inhibition of jnk activation may be involved in the suppressive effects of ketamine on snl-induced spinal astrocyte activation. therefore,inhibition of spinal jnk activation may be involved in the analgesic effects of ketamine on snl-induced neuropathic pain. © 2011 mei et al; licensee biomed central ltd.