Objective To investigate the changes in histamine level in striatum in rats with neuropathic pain and to find out if histamine has any analgesic effect on neuropathic pain.Methods The experiment was performed in 4 parts.In partⅠ24 healthy male SD rats weighing 180-250g were randomly divided into 2 groups(n =12 each):control group received sham operation and neuropathic pain group in which left sciatic nerve was partially ligated.Two weeks after operation microdialysis catheter was inserted into right striatum and fixed.The microdialysate was collected for determination of histamine concentration.In partⅡanother 24 healthy male SD rats were randomly divided into control group and neuropathic pain group as in partⅠ.Metoprine 5 mg?kg~(-1)(a L- histidine decarbonase inhibitor)was injected intraperitoneally(IP)in both groups.Then microdialysate was collected from striatum once an hour for 5 h for determination of histamine concentration and the withdrawal threshold to von Frey hair stimulation of the plantar surface of the left hindpaw was measured at 5 h after IP metoprine.In partⅢandⅣthe effects of intracerebral-ventricular histamine 30?g or 300?g and IP L-histidine 500 mg?kg~(-1) on mechanical pain threshold were measured in rats with neuropathic pain.Results In partⅠthere was no significant difference in the extracellular concentration of histamine in the striatum between the two groups. In partⅡthe extracellular concentration of histamine in the striatum was increased after IP metoprine in both groups but the increase was significantly larger in neuropathic pain group than in control group.The pain threshold was also significantly increased in neuropathic pain group after IP metoprine.In partⅢandⅣintracerebral- ventricular histamine 30?g or IP L-histidine 500 mg?kg~(-1) induced hyperalgesia while intracerebral-ventricular histamine 300?g produced analgesia in rats with neuropathic pain.Conclusion The histamine metabolism is more active in the striatum in rats with neuropathic pain.The neuropathic pain is ameliorated by large dose of histamine administered in cerebral-ventricle and metoprine can induce accumulation of histamine in the striatum.