| In this experiment, nefopam was used as the main object in the postoperative analgesia of dogs, jointed with tetrahydropalmatine or lappaconitine, and explored the dose of the joint drug. Measured pain threshold of rats with the YLS-3E electronic pressure tenderness to determine the dose of joint analgesic drug, set up the laparotomy exploration model in the rats to compare analgesic effect of two joint drugs, simultaneously established the ovariohysterectomy model in dogs to verify the effectiveness, applicability and safety of them, and provided the basis of theoretical and experimental for clinical application and popularization in small animals.The research including:(1) Determined the best doses of analgesic drugs. 90 wistar rats were divided into nine groups, high, medium and low dose groups of nefopam, tetrahydropalmatine and lappacontine, applied electronic pressure tenderness to measure pain threshold of rats, and observed the change of the rats pain threshold to determine the optimal dose of drugs.(2) To compare the effect of compound analgesic drugs. 80 wistar rats, were divided into eight groups, respectively nefopam with tetrahydropalmatine compound group: N75-T75 group, N75-T50 group,N50-T75 group, N50-T50 group, and nefopam with lappacontine compound group: N75-L75 group, N75-L50 group, N50-L75 group and the N50-L50 group, compared the pain threshold change of each group, selected the group which its pain threshold increased significantly as the best analgesia group.(3) Efficacy assessment of postoperative. 40 wistar rats were randomly divided into 4 groups, including nefopam with tetrahydropalmatine group(NFP-T group), the nefopam group(NFP group), tramadol group(TR group), blank control group(SAL group), and the dose of NFP-T group received from the second phase, NFP group was given with nefopam hydrochloride at 100μg/10 g, TR group was given tramadol hydrochloride at 72μg/10 g. Laparotomy model in rats was established, and the drugs were given 1h before operation by intraperitoneal injection, observed specificity pain behavior of rats after operation to assesse the analgesic effect of the joint drugs.(4) The clinical application of the joint drug. 24 local healthy dogs were divided into three groups, including nefopam joint group(NFP-THP group), nefopam control groud(NFP group, intravenous injection of 1 mg/kg nefopam hydrochloride injection) and tramadol group(TR group, intravenous injection of 2 mg/kg of tramadol hydrochloride injection). Ovariohysterectomy pain model in dogs was setted up, each dog received immediately analgesic drugs after surgery, scored by Glasgow composite pain score, and recorded respiration rate, heart rate at 2h,4h,8h,12 h,24h after surgery, collectted blood samples at 4h, 8h, 24 h after the administration to detect the change of biochemical parameters of liver and kidney function.Results showed that:(1) The best analgesic dose of three drugs in rats are that nefopam is 100μg/10 g, tetrahydropalmatine is 100μg/10 g., lappaconitine is 22μg/10 g.(2) Analgesic strength of the N75-T75 group is equal to 72μg/10 g of tramadol or 100μg/10 g of nefopam. Each group of the lappacontine did not show better analgesic effect.(3) In the laparotomy model in rats, the behavior score of N75-L75 group was significantly lower than the other three groups(P <0.05), and it showed that analgesic strength of the joint group is higher than 72μg/10 g of tramadol hydrochloride or 100μg/10 g of nefopam, and the joint drugs can provide effective analgesia after surgery in rats.(4) In the ovariohysterectomy model in dogs, the score of the joint group is significantly lower than TR group and NFP group during 2-6h after the surgery(P <0.05), the score of 8-24 h after surgery is no significant difference among groups(P >0.05). Respiration rate has significant differences with NFP group during 4-8h after surgery(P <0.05), has significant difference with TR group during 8-12 h after surgery(P >0.05), heart rate of NFP-THP group has no significant difference with TR groups and NFP group during 2-12 h after surgery(P> 0.05), and biochemical indices of liver and kidney have no abnormal values 24 h after surgery, and have no significant difference with NFP group and TR group(P <0.05).We conclude that:(1) The joint drugs of compounding 1mg/kg of nefopam and 1mg/kg of tetrahydropalmatine can provide better analgesic strength than 2mg/kg of tramadol within 6h after operation of dog, and they have the similar effect after that.(2) The joint drug of compounding 1mg/kg nefopam and 1mg/kg tetrahydropalmatine can effectively improve physiological function after surgery, and have no significant impact on primary biochemical parameters of liver and kidney. |
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