The Efficacy And Mechanism Of Diclofenac Sodium On The Neuropathic Pain In Rats

ObjectiveTo obseve the effects of diclofenac sodium on mechanical hyperalgia, substance P (SP) and calcitonin gene-related peptide (CGRP) expression in dorsal root ganglion (DRG) neurons and dorsal horn, as well as the structure of gastrointestinal mucosa in chronic constriction injury (CCI) rats.Materials and MethodsForty male SD rats weighing 240-260g were randomly divided into 5 groups : 1) Sham operation group; 2) Control group ( treated with CCI) ; 3) diclofenac sodium 2mg/kg group; 4) diclofenac sodium 4mg/kg group; 5) diclofenac sodium 10mg/kg group . From 8th day post-ligation. Nature saline, different dose of diclofenac sodium were administered by injecting into gastric cavity twice per day for 7 days according to different groups, respectively. Before and after drug injection(at 1^st,3^rd,5^th,7^th day), the posterior Paw Withdrawal Mechanical Threshold (PWMT) was measured by Von Frey hair, and the expressions of SP and CGRP in L4-5 dorsal root ganglion (DRG) neurons and dorsal horn were detected by immunohistochemistry method. Meanwhile, the structure of gastrointestinal mucosa was observed in light microscope.Results(1) The effects of diclofenac sodium on PWMTAt pre-drug , different time post-drug, the right posterior PWMTs of Control group, diclofenac sodium 2mg/kg group, 4mg/kg group, 10mg/kg group were significantly decreased compared with that of Sham operation group (p<0.01). At 5^th and 7^th day post-drug, the PWMTs of 4mg/kg group were significantly increased compared with that of pre-durg and control group(P<0.01或P<0.05). At different time post-drug, the PWMTs of10mg/kg group were significantly increased compared with that of pre-durg and control group(P<0.01). and the effect of diclofenac sodium was dose-dependent (p<0.05).(2) The effects of diclofenac sodium on the structure of gastrointestinal mucosa.At 7^th day post-drug, there were no any ulcer and bleeding in gastrointestinal mucosa of all five groups macroscopically. Under microscope, in Sham operation and Control group, the structure of gastrointestinal mucosa was intact without obvious inflammatory cells soakage. In 2mg/kg group, the structure of gastric mucosa was slightly incrassate, but the intestinal mucosa was intact. In 4mg/kg group, gastric mucosa gland became minor, the wall of the gland became tenuis, intestinal villi became minor and short, beaker cell decreased. In 10mg/kg group, gastric mucosa gland was hyperplastic and incrassate, intestinal villi became minor and short, acidophilic cell increased with inflammatory cells soakage.(3) The effects of diclofenac sodium on SP and CGRP expressions in DRG neuronsAt 7^th day post-drug, in Control group, diclofenac sodium 2mg/kg group, 4mg/kg group, 10mg/kg group, the average optical density (OD) of SP and CGRP in the right L4-5 DRG neurons were significantly increased compared with that of sham operation group(P <0.01).In 4mg/kg group, 10mg/kg group, the average optical density (OD) of SP and CGRP in the right L4-5 DRG neurons were significantly decreased compared with that of control group(P<0.01或P<0.05).(4) The effects of diclofenac sodium on SP and CGRP expressions in the I, II layerof dorsal horn.At 7^th day post-drug, in Control group, diclofenac sodium 2mg/kg group, 4mg/kg group, 10mg/kg group, the average optical density (OD) of SP and CGRP in the dorsal horn were significantly increased compared with that of sham operation group(P <0.01).In 4mg/kg group, 10mg/kg group, the average optical density (OD) of SP and CGRP in the dorsal horn were significantly decreased compared with that of control group(P<0.01或P<0.05).ConclusionsDiclofenac sodium can dose-dependently (4mg/kg,10mg/kg) decrease the mechanical hyperalgia. The possible mechanism might be reducing SP and CGRP expressions in DRG neurons and dorsal horn in CCI rats; When administerd in large dose, it can damage gastrointestinal mucosa obviously, thus this dose shoud be cautious in rats and we should constrain dose in clinic.