Objective To evaluate the effect of amitriptyline on the phosphorylation of histone deacetylase 5 (HDAC5) in the basolateral amygdala (BLA) of rats with neuropathic pain.Methods Thirty healthy male Wistar rats,weighing 250-300 g,were divided into 3 groups (n=10 each) using a random number table method:sham operation group (S group),neuropathic pain group (NP group) and amitriptyline group (A group).Spared nerve injury was produced by exposing the sciatic nerve and its branches and ligation and transection of tibial nerve and common fibular nerve in anesthetized rats.Amitriptyline 10 mg/kg was intraperitoneally injected every day on 14-35 days after establishing the model in group A,while the equal volume of normal saline was given instead of amitriptyline in S and NP groups.The mechanical paw withdrawal threshold (MWT) was measured on 3,7,14,21,28 and 35 days after establishing the model in each group.The forced swimming test was performed on day 36 after establishing the model,and immobility time,climbing time and swimming time were recorded.The rats were then sacrificed,and brain tissues in BLA were obtained for determination of the expression of HDAC5 and phosphorylated HDAC5 (p-HDAC5) (by Western blot) and expressionof HDAC5 mRNA (by real-time quantitative polymerase chain reaction).Results Compared with group S,the MWT was significantly decreased at each time point,the immobility time was prolonged,and the swimming time and climbing time were shortened in group NP,and the MWT was significantly decreased on days 14,21 and 28 after establishing the model,the expression of p-HDAC5 was down-regulated,and the expression of HDAC5 mRNA was up-regulated in group A (P＜0.05).Compared with group NP,the MWT was significantly increased on days 21,28 and 35 after establishing the model,the immobility time was shortened,the climbing time was prolonged,the expression of p-HDAC5 was up-regulated,and the expression of HDAC5 mRNA was down-regulated in group A (P＜0.05or 0.01).Conclusion The mechanism by which amitriptyline improves depression is associated with promoting the phosphorylation of HDAC5 in BLA of rats with NP.