动物疼痛评估及建议用药
发布科室：动物实验室 时间：2015年04月13日
第二部分 动物疼痛评估及建议用药
1. USDA Pain and Distress Classifications and Examples
Classification B: 为了进行教学、测试、实验、研究或手术动物已被饲养或保定，但尚未进行上述操作者。Animals being bred, conditioned, or held for use in teaching, testing, experiments, research, or surgery, but not yet used for such purposes.
Examples:
Breeding colonies of any animal species (USDA does not require listing of rats, mice, birds) that are held in legal sized caging and handled in accordance with the Guide and other applicable regulations. Breeding colony includes parents and offspring.
Newly acquired animals that are held in proper caging and handled in accordance with applicable regulations.
l Animals held under proper captive conditions or wild animals that are being observed.
Classification C: 动物进行不致引起疼痛紧迫的教学、测试、实验、研究或使用减轻疼痛的药物者。Animals upon which teaching, research, experiments, or tests will be conducted involving no pain, distress, or use of pain-relieving drugs.
Examples:
l Procedures performed correctly by trained personnel such as the administration of electrolytes/fluids, administration of oral medication, blood collection from a common peripheral vein per standard veterinary practice (dog cephalic, cat jugular) or catheterization of same, standard radiography, parenteral injections of non-irritating substances.
l Euthanasia performed in accordance with the recommendations of the most recent AVMA Panel on Euthanasia, utilizing procedures that produce rapid unconsciousness and subsequent humane death.
l Manual restraint that is no longer than would be required for a simple exam; short period of chair restraint for an adapted nonhuman primate.
Classification D: 动物进行引起疼痛紧迫的教学、测试、实验、研究或手术，且可使用适当的麻醉药、止痛药或镇静药者。Animals upon which experiments, teaching, research, surgery, or tests will be conducted involving accompanying pain or distress to the animals and for which appropriate anesthetic, analgesic, or tranquilizing drugs will be used.
Examples:
l Surgical procedures conducted by trained personnel in accordance with standard veterinary practice such as biopsies, gonadectomy, exposure of blood vessels, chronic catheter implantation, laparotomy or laparoscopy.
l Blood collection by more invasive routes such as intracardiac or periorbital collection from species without a true orbital sinus such as rats and guinea pigs.
l Administration of drugs, chemicals, toxins, or organisms that would be expected to produce pain or distress but which will be alleviated by analgesics.
Classification E: 动物进行引起疼痛紧迫的教学、测试、实验、研究或手术，但因麻醉药、止痛药或镇静药的使用会对上述目的结果有负面影响而不能使用者。Animals upon which teaching, experiments, research, surgery, or tests will be conducted involving accompanying pain or distress to the animals and for which the use of appropriate anesthetic, analgesic, or tranquilizing drugs will adversely affect the procedures, results, or interpretation of the teaching, research, experiments, surgery, or tests.
Examples:
l Procedures producing pain or distress unrelieved by analgesics such as toxicity studies, microbial virulence testing, radiation sickness, and research on stress, shock, or pain.
l Surgical and postsurgical sequella from invasion of body cavities, orthopedic procedures, dentistry or other hard or soft tissue damage that produces unrelieved pain or distress.
l Negative conditioning via electric shocks that would cause pain in humans.
Chairing of nonhuman primates not conditioned to the procedure for the time period used.
2. 实验造成的疼痛及焦虑分级表（USDA Pain Levels）
|
等级
|
等级B
Category B
|
等级C
Category C
|
等级D
Category D
|
等级E
Category E
|
|
说明
|
仅代养、繁殖，未进行实验操作
|
轻微疼痛
不需用药缓解
|
明显疼痛
需用药缓解
|
明显疼痛
不用药缓解
|
|
实例
|
|
1. 保定、秤重
2. 注射、采血
3. 打耳号
4. 人道安乐死
5. 不会造成动物生理状况明显改变的实验
|
1. 穿刺采样
2. 存活与非存活性手术
3. 眼窝采血
4. 食欲丧失
5. 皮肤创伤
6. 结膜炎
7. 角膜水肿
8. 传染病诱发
|
1. 毒性试验、微生物试验或肿瘤试验导致动物重病或濒死
2. 眼睛或皮肤的刺激性试验导致严重临床症状
3. 禁水、禁食时间过长
4. 长时间或重复性电击
5. 烧伤或大规模皮肤创伤
6. 不人道处死
|
|
规范
|
无
|
无
|
应遵守麻醉及镇痛药品使用规范，正确及时给药
|
若必需进行此类实验，应于动物实验申请书说明原因及实验终点的判断
|
3. 辨识疼痛与焦虑（Recognition of Pain and Distress）
Animals should be monitored for pain and distress as appropriate for the condition, procedure and degree of invasiveness. Critical to the assessment of the presence or absence of pain or distress is having the ability to distinguish between normal and abnormal animal behavior. This is especially true when dealing with rodents that often exhibit pain and distress with only subtle changes in their behavior.
应监控动物的疼痛与焦虑来判定对动物的影响程度。相关人员需有能力区别正常与异常的动物行为，来评估动物是否疼痛或焦虑。在啮齿类实验动物，行为的细微变化可真实反应出这些动物的疼痛与焦虑状态。
常见的行为变化如下表：
|
1) Lethargy 不活泼
|
reluctance to move 活动力降低
|
|
2) Abnormal posture 姿势异常
|
Hunched 拱背
|
|
3) Restlessness 躁动
|
pacing, constant motion 踱步、持续运动
|
|
4) Self-mutilation 自残
|
licking, biting, scratching, rubbing 舔，咬，抓，摩擦
|
|
5) Vocalization 发出叫声
|
squeaking when handled 抓取动物时发出叫声
|
|
6) Aggression 出现攻击性
|
biting when handled 抓取动物时咬人
|
|
7) Guarding 警觉状
|
attempting to move away or protect painful area
试图逃脱或保护疼痛的区域
|
|
8) Lack of Grooming 缺乏理毛
|
ruffled or greasy fur coat 毛发粗钢或油腻
|
|
9) Red staining of face 颜面色染
|
red discharge from eyes or nose (rats)
眼鼻出现红色分泌物(大鼠)
|
|
10) Poor appetite 食欲差
|
|
|
11) Weight loss 体重降低
|
loss of >10% of pre-operative body weight
与术前相较，体重降低10％以上
|
4. 用药建议（Recommendation of Analgesics for Use in Small Mammals and Larger Animals）
|
Analgesic
|
Mouse
|
Rat
|
Rabbit
|
Dog
|
Pig
|
|
Opioids
|
|
Buprenorphine
|
0.1 mg/kg SC
|
0.05 mg/kg SC
|
0.01-0.05mg/kg SC
|
0.005-0.02mg/kg IM SC or IV every 6-12 hours
|
0.005-0.02mg/kg IM or IV every 6-12 hours
|
|
Butorphanol
|
1-5 mg/kg SC
|
2 mg/kg SC
|
0.1-0.5 mg/kg SC
|
0.2-0.4 mg/kg SC or IM, every 3-4 hours
|
unknown
|
|
Morphine
|
2-5 mg/kg SC or IM every 4 hours
|
2-5 mg/kg SC or IM every 4 hours
|
2-5 mg/kg SC or IM every 4 hours
|
0.5-5 mg/kg IM every 4 hours
|
0.2-1 mg/kg IM every 4 hours
|
|
Pethidine
|
10-20 mg/kg SC or IM every 2-3 hours
|
10-20 mg/kg SC or IM every 2-3 hours
|
10 mg/kg SC or IM every 2-3 hours
|
10 mg/kg IV or IM every 2-4 hours
|
2 mg/kg IV or IM every 2-4 hours
|
|
NSAIDS
|
|
Ibuprofen
|
30 mg/kg PO, SID
|
15 mg/kg PO, SID
|
unknown
|
unknown
|
unknown
|
|
Carprofen
|
5 mg/kg SC, BID
|
5 mg/kg SC, BID
|
1.5 mg/kg daily, 4 mg/kg SC daily
|
4 mg/kg SC or IV, SID
|
2-4 mg/kg SC or IV once daily (probably 2-3 days)
|
|
Ketoprofen
|
unknown
|
5 mg/kg IM
|
3 mg/kg IM
|
2 mg/kg SC daily (up to 3 days)
|
3 mg/kg SC (once)
|
|
Flunixin
|
2.5 mg/kg SC, BID
|
2.5 mg/kg SC, BID
|
1.1 mg/kg SC, BID
|
1 mg/kg IV or IM every 12 hours (up to 3 days)
|
1 mg/kg IV or SC, SID
|
|
Meloxicam
|
1 mg/kg IM. IP, or SC, SID
|
1.0-2.0 mg/kg SC, SID
|
0.2 mg/kg SC, SID
|
0.2 mg/kg SC, SID
|
0.4 mg/kg once daily IM (for 2 days)
|
|
Acetaminophen
|
Not recommended
|
Not recommended
|
100-300 mg/kg every 4 hours, or 1-2mg/ml drinking water
|
5-15 mg/kg BID to TID
|
unknown
|
|
Analgesic
|
Mouse
|
Rat
|
Rabbit
|
Dog
|
Pig
|
参考文献：
1. 周玉京. 评估与舒缓实验动物之紧迫（Stress）与困扰（Distress）. 中华实验动物学会第21期会讯，台北，台湾，2008.
2. 实验动物管理与使用指南. 2005. 中华实验动物学会出版.
3. FELASA Working Group on Pain and Distress. (1994) Pain and diatress in laboratory rodents and lagomorphs. Laboratory Animals. 28: 97-112.
4. 动物疼痛评估及建议用药(2). 高雄医学大学附设中和纪念医院实验动物中心.
附件下载：