Because the anatomic structures and neurophysiologic mechanisms leading to the perception of pain are similar in humans and non-human animals, it is reasonable to assume that if a stimulus:

• is painful to humans,
• is damaging or potentially damaging to tissues, or
• induces escape and emotional responses in an animal,

it must be considered to be painful to that animal.

The choice of post-surgical analgesic drug must take into consideration (and be appropriate for) the estimated level and duration of post-surgical/post-procedural pain/discomfort associated with the specific surgery/procedure.

Generally speaking, analgesics should be provided as early in the exercise as possible. Providing analgesic PRIOR to the initiation of the painful stimulus is most preferred; providing analgesia during the procedure (of an anesthetized animal) is considered the minimal standard when pre-procedural analgesia is not possible.

This concept of pre-emptive analgesic is important to the stability of the research animal and the outcome of the research data.  An additional benefit of pre-emptive analgesia is that the amount of anesthetics required for proper anesthesia are often reduced, further benefiting the animal with a rapid return to normal, while saving critical research dollars.

For analgesic drugs that are administered via the oral route, the drug must:

• be administered via oral gavage at the appropriate dosing frequency, or
• if administered via the drinking water, the drug must be placed in the drinking water starting a minimum of 7 days prior to the surgery/painful procedure in order for the animal to be “exposed”, and, presumably, adapted to the altered taste of the water at the time of the surgery/procedure. This prepatory step is necessary to overcome ‘neophobia,’ a behavioral adaptation of rodents (especially rats) whereby they may not consume adequate quantities of fluids when a new taste sensation is recognized. Placing a flavored analgesic in the water post procedure may allow for association of the ‘pain’ with the new flavor and thereby rejection of the flavored water resulting in inadequate analgesia.

Duke utilizes a tiered system of analgesic delivery, based upon generalized observations of degrees of pain or discomfort.  These include:

P1: Survival Surgery/Survival Procedures Estimated to Cause MARKED Post-Surgery/Post-Procedural Pain

P2: Survival Surgery/Survival Procedures Estimated to Cause MODERATE Post-Surgery/Post-Procedural Pain
P3: Survival Surgery/Survival Procedures Estimated to Cause MILD Post-Surgery/Post-Procedural Pain

P1:  Survival Surgery/Survival Procedures Estimated to Cause MARKED Post-Surgery/Post-Procedural Pain.  (Examples: any surgery involving thoracotomy or celiotomy; transplantation of an organ; limb amputation; extensive orthopedic surgery; cecal ligation and puncture):

• Drug	Mouse	Rat	Hamster	Gerbil	Guinea Pig
  Morphine	10 mg/kg SQ or IM every 4 hours	10 mg/kg SQ or IM every 4 hours	10 mg/kg SQ or IM every 4 hours	10 mg/kg SQ or IM every 4 hours	10 mg/kg SQ or IM every 4 hours
  Codeine	20 mg/kg SQ every 4 hours	50 mg/kg SQ every 4 hours			40 mg/kg SQ every 4 hours
  Oxymorphone	0.15 mg/kg SQ or IM every 4 hours	0.22-0.33 mg/kg SQ every 4 hours	0.2-0.5 mg/kg SQ or IM every 6 hours	0.2-0.5 mg/kg SQ or IM every 6 hours

 P2:  Survival Surgery/Survival Procedures Estimated to Cause MODERATE Post-Surgery/Post-Procedural Pain   (Examples: most laparoscopic (i.e. intra-abdominal) surgeries; limited orthopedic surgery; intra-cranial surgery):

• Drug	Mouse	Rat	Hamster	Gerbil	Guinea Pig
  Ketoprofen	5mg/kg SQ SID	5mg/kg SQ SID	5mg/kg SQ SID	5mg/kg SQ SID	5mg/kg SQ SID
  Meperidine	20 mg/kg SQ or IM every 3 hours	20 mg/kg SQ or IM every 3 hours	20 mg/kg SQ or IM every 3 hours	20 mg/kg SQ or IM every 3 hours
  Nalbuphine	4-8 mg/kg SQ or IM every 3 hours	2-5 mg/kg SQ every 4 hours	4-8 mg/kg SQ or IM every 3 hours	4-8 mg/kg SQ or IM every 3 hours	1-2 mg/kg IM every 4 hours
  Pentazocine	10 mg/kg SQ every 4 hours	10 mg/kg SQ every 4 hours
  Butorphanol	2 mg/kg SQ every 4 hours	5 mg/kg SQ every 4 hours	5 mg/kg SQ every 4 hours	5 mg/kg SQ every 4 hours
  Buprenorphine	0.05-0.1 mg/kg SQ every 12 hours	0.1-0.5 mg/kg SQ every 12 hours	0.5 mg/kg SQ every 8 hours	0.2 mg/kg every 8 hours	0.05 mg/kg SQ every 12 hours
  Carprofen	5 mg/kg SQ every 12 hours	5 mg/kg SQ every 12 hours
  Aspirin	300 mg/kg orally every 24 hours	100 mg/kg orally every 24 hours			86 mg/kg orally every 24 hours
  Ibuprofen	7.5 mg/kg orally every 24 hours	30 mg/kg orally every 24 hours
  Phenylbutazone	30 mg/kg orally every 24 hours	20 mg/kg orally every 24 hours			40 mg/kg orally every 24 hours
  Acetaminophen	300 mg/kg orally every 24 hours	300 mg/kg orally every 24 hours

 P3:  Survival Surgery/Survival Procedures Estimated to Cause MILD Post-Surgery/Post-Procedural Pain:  (Examples: Placement of subcutaneous tumors or subcutaneous osmotic pumps; placement of chronic indwelling vascular cannulaes; orchiectomy) 

• Drug	Mouse	Rat	Hamster	Gerbil	Guinea Pig
  Ketoprofen	5mg/kg SQ SID	5mg/kg SQ SID	5mg/kg SQ SID	5mg/kg SQ SID	5mg/kg SQ SID
  Flunixin			2.5 mg/kg IM every 12 hours	2.5 mg/kg IM every 12 hours
  Aspirin	300 mg/kg orally every 24 hours	100 mg/kg orally every 24 hours			86 mg/kg orally every 24 hours
  Ibuprofen	7.5 mg/kg orally every 24 hours	30 mg/kg orally every 24 hours
  Phenylbutazone	30 mg/kg orally every 24 hours	20 mg/kg orally every 24 hours			40 mg/kg orally every 24 hours
  Acetaminophen	300 mg/kg orally every 24 hours	300 mg/kg orally every 24 hours

SQ=subcutaneous
IM=intramuscular

 For purposes of administering a drug via the drinking water:

• 	Rat	Mouse	Hamster	Gerbil	Guinea Pig
  Normal* Daily Water Consumption	8-11 ml/100 gm  body weight/day	15 ml/100 gm body weight/day	30 ml/day	4-7 ml/100gm body weight/day	10 ml/100 gm body weight/day

 *Animals that have been subjected to a painful procedure/surgery will not drink the “normal” amount of water for a minimum of 24 hours post-surgery/post-procedure.    It is estimated that normal water consumption will be reduced by at least 50%. 

 Amount of orally-administered drug to mix/administer per ml of drinking water: 

• Drug	Rat-Normal Water Consumption	Rat-50% Decrease in Water Consumption	Mouse-Normal Water Consumption	Mouse-50% Decrease in Water Consumption	Guinea Pig-Normal Water Consumption	Guinea Pig-50% Decrease in Water Consumption
  Aspirin	0.9 mg/ml	1.8 mg/ml	2 mg/ml	4 mg/ml	0.9 mg/ml	1.8 mg/ml
  Ibuprofen	0.3 mg/ml	0.6 mg/ml	.05 mg/ml	0.1 mg/ml
  Phenylbutazone	0.2 mg/ml	0.4 mg/ml	0.2 mg/ml	0.4 mg/ml	0.4 mg/ml	0.8 mg/ml
  Acetaminophen	2.7 mg/ml	5.4 mg/m	2.0 mg/ml	4.0 mg/ml

 Local Anesthetics:  Even with general anesthesia, the topical, subcutaneous (at surgical incision site), intra-articular, etc. administration of a local anesthetic is recommended in order to provide additional post-surgical analgesia.  Local anesthetics should not be used alone to provide post-surgical/post-procedural analgesia.

• Agent	Potency (Procaine=1)	Onset	Duration*	Topical Use	Infiltration Use	Nerve Block Use
  Procaine (Novacaine)	1	Slow	30-90 minutes	-	1-2%	1-2%
  Chloroprocaine (Nesacaine)	2.4:1	Fast	Up to 2 hours	-	1-2%	1-2%
  Lidocaine (Xylocaine)	2:1	Fast	2 hours	2-4%	0.5-2%	0.5-2%
  Mipivacaine (Carbocaine)	2.5:1	Fast	2-4 hours	-	1-2%	1-2%
  Tetracaine (Ponticaine)	12:1	Slow	3-8 hours	0.2%	0.1%	0.1%
  Hexycaine (Cyclaine)	1-2:1	Fast	3-6 hours	5%	0.5-1%	2%
  Bupivicaine (Marcaine)	8:1	Intermediate	24 -48 hours	-	0.25%	0.5%

 * Duration is given for larger species.  Duration in rodents (with their higher metabolic rate) should be considered less.