| Objective To observe the effect of electroacupuncture of different frequencies on alleviating pain responses in a rat model of acute gout arthritis;To investigate the involvement of opioid peptides in electroacupuncture-induced alleviation of pain responses of rat model of acute gout arthritis.Methods Part 1(1)Healthy adult male Sprague-Dawley(SD)rats were randomly divided into Vehicle group and MSU group.Rats of MSU group were injected with1.25 mg/50 μl monosodium urate in the rear side of left ankle in 30-40° angle,following the interior side of Achilles tendon.Rats of Vehicle group were injected with the same volume of phosphate buffered saline(PBS).The mechanical paw withdrawal threshold(PWT),thermal paw withdrawal latency(PWL),ongoing pain score and the ankle swelling of these two groups were measured before and 2 h,6 h,8h,24 h and 48 h after the model establishment.(2)Healthy adult male SD rats were randomly divided into Vehicle group and MSU group.Rats of MSU group were injected with 1.25 mg/50 μl monosodium urate in the rear side of left ankle in 30-40°angle,following the interior side of Achilles tendon.Rats of Vehicle group were injected with the same volume of PBS.We evaluated the pathology changes of ankle synovial tissue after the model establishment.Part 2(1)Healthy adult male SD rats were randomly divided into Vehicle group,MSU group,2Hz EA group,100 Hz EA group,2/100 Hz EA group and Sham EA group.Acute gout arthritis was established in each group as indicated above in part 1.Rats were treated with EA at 8 h and 24 h after the model establishment.Electroacupuncture(Corresponding frequency,starting at 0.5 m A,plus 0.5m A per minutes,total 30 min)was administered at bilateral points Zusanli(ST36)and Kunlun(BL60).Sham EA: needles were only inserted into the skin without power supply.The PWT was measured before and 4 h,8 h,24 h and 48 h after the model establishment.(2)Healthy adult male SD rats were randomly divided into Vehicle group,MSU group,2/100 Hz EA group and Indomethacin(Indo)group.The model establishment and EA treatment were as the same as part 1.Indomethacin(10 mg/kg,i.p.)was injected intraperitoneally at 8h after model establishment in Indo group.The PWT was measured before model establishment and 4 h,8 h thereater.EA group was treated with electroacupuncture and the Indo group were injected with indomethacin at 7.5h after the model establishment.Part 3(1)Healthy adult male SD rats were randomly divided into Vehicle group,MSU group,EA group,EA+NALX group,EA+IL NALX group,EA+CL NALX group.The model establishment and EA treatment were as the same as part2.Rats of EA group were injected with the same volume of PBS.Rats of the EA+NALX group was injected with naloxone(2mg/kg,i.p.)intraperitoneally at 0.5h before EA treatment.Rats of the EA+IL NALX group and EA+CL NALX group were injected with naloxone(40 μg /kg)into ipsilateral(IL)or contralateral(CL)ankle joint respectively at 0.5h before EA treatment.In addition to the Vehicle group and MSU group,each group was treated with electroacupuncture at 7.5h after the model establishment.PWT was measured before model establishment and 4 h,8 h thereafter.(2)Healthy adult male SD rats were randomly divided into Vehicle group,MSU group,EA group,EA+β-FNLT group,EA+NLTD group,EA+Nor-BNI group The model establishment and EA treatment were as the same as part 2.β-funaltrexamine(50 μg/ankle),naltrindole(76 μg/ankle)and norbinaltorphimine(48.7 μg/ankle)was respectively injected into the ipsilateral side ankle of rats of EA+β-FNLT group,EA+NLTD group,EA+Nor-BNI group.Each group was treated with electroacupuncture at 7.5h after the model establishment except Vehicle and MSU group.PWT was measured before model establishment and4 h,8 h thereafter.(3)Healthy adult male SD rats were randomly divided into Vehicle group,MSU group,EA group,EA+CL β-FNLT group,EA+CL NLTD group and EA+CL Nor-BNI group.The model establishment and EA treatment were as the same as part 2.β-funaltrexamine(50 μg/ankle),naltrindole(76 μg/ankle)and norbinaltorphimine(48.7 μg/ankle)was respectively injected into the contralateral side ankle of rats of EA+CL β-FNLT group,EA+CL NLTD group and EA+CL Nor-BNI group.Each group was treated with electroacupuncture at 7.5h after the model establishment except Vehicle and MSU group.PWT was measured before model establishment and 4 h,8 h thereafter.(4)Healthy adult male SD rats were randomly divided into Vehicle group,MSU group,IL DAMGO group,CL DAMGO group,IL U50488 group,CL U50488 group.DAMGO(4.9 μg/ankle)or U50488(1μg/ankle)was respectively injected into the ipsilateral ankle of rats of DAMGO group and U50488 group.PWT was measured before model establishment and 6h,8h thereafter.(5)Healthy adult male SD rats were randomly divided into Vehicle group,NALX group,β-FNLT group,NLTD group and Nor-BNI group.Naloxone(2mg/kg),β-funaltrexamine(50 μg/ankle),norbinaltorphimine(48.7 μg/ankle)or naltrindole(76μg/ankle)was respectively injected into the left ankle of rats of NALX group,β-FNLT group,Nor-BNI group and NLTD group.Rats of Vehicle group were injected with the same volume of PBS.PWT of left ankle of rats was measured before drugs injection and 4h thereafter.Results Part 1(1)2h after the model establishment,MSU group showed obvious ankle joint swelling compared with Vehicle group.The swelling lasted up to 48 h.MSU group showed obvious ongoing pain behavior and PWT began to decline significantly 2h after model establishment(P<0.05).4 h after the model establishment,PWL also exhibited significant decline(P<0.05).These pain-related behaviors lasted until 24 h after the model establishment(P<0.01).(2)MSU group showed extensive inflammatory cell infiltration compared with Vehicle group.Part 2(1)Compared with MSU group,PWT in 2Hz EA group and Sham EA group showed no difference(P>0.05),PWT in 100 Hz EA group increased significantly(P<0.05),and PWT in 2/100 Hz EA group increased significantly(P<0.01).(2)Compared with MSU group,PWT in Indo group increased(P<0.05),PWT in 2/100 Hz EA group increased significantly(P<0.01);The increase of PWT in 2/100 Hz EA group is comparable with Indo group(P<0.05).Part 3(1)Compared with EA group,PWT in EA+NALX group and EA+IL NALX group decreased significantly(P<0.01),PWT in EA+CL NALX group showed no difference(P>0.05).(2)Compared with EA group,PWT in EA+β-FNLT group and EA+Nor-BNI group decreased significantly(P<0.01),PWT in EA+NLTD group showed no difference(P>0.05).(3)Compared with EA group,PWT in EA+CL β-FNLT group,EA+CL NALX group and EA+CL NLTD group showed no difference(P>0.05).(4)Compared with MSU group,PWT in IL DAMGO group and IL U50488 group increased significantly(P<0.01),PWT in CL DAMGO group and CL U50488 group showed no difference(P>0.05).(5)Compared with Veh group,the PWT in NALX group,β-FNLT group,NLTD group and Nor-BNI group were no difference(P>0.05).Conclusions Our study demonstrated that 100 Hz EA and 2/100 Hz EA effectively alleviates pain response in a rat model of acute gout arthritis,of which 2/100 Hz EA showed better therapeutic potentials;The analgesic effect of EA on acute gout arthritis is largely mediated via peripheral μ and κ-opioid receptors. |
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