Analgesia (Guideline)

Guidelines: The IACUC has provided a set of guidance documents (Policies, Guidelines, and Informational Sheets) for use when planning animal procedures at the University of Iowa. An exception to a Guideline must be described and justified in the Animal Protocol and approved during the normal review process.

Purpose

The purpose of these guidelines is to describe appropriate analgesia regimens for the management of pain in animals used in teaching, research and testing at the University of Iowa. These guidelines include minimum analgesia recommendations. Animals should be monitored for an appropriate time period to determine if analgesia provisions are adequate. Any animal showing evidence of pain should be provided analgesia. If analgesia cannot be provided due to scientific reasons, the rationale should be described and approved in the Animal Protocol.

Recognition of Pain

Adequate alleviation of pain in laboratory animals requires the training and knowledge to recognize signs of pain which may differ between species. An information sheet titled “Pain Recognition in Laboratory Animals” is provided for reference, and veterinary consultation is available for personnel training and advice on pain recognition in unique models.

Pre-Emptive Use of Analgesic Agents

Pre-emptive analgesia should be provided whenever possible. Analgesia provisions are most effective at reducing the intensity of painful stimulation when given prior to the painful event.

Advantages of pre-emptive use of analgesics:
- Reduces the intensity of painful stimulation
- Improves the animal's comfort level after surgery
- Decreases the amount of anesthesia required to maintain a surgical plane
- Results in a smoother recovery

Multi-Modal Use of Analgesic Agents

Multi-modal analgesia (giving multiple drugs with different mechanisms of action) provides the best analgesia possible
- e.g., local analgesia + opioid + NSAID (when appropriate)
- Classes, dosages, routes and frequency of administration are listed in the “Common Analgesic Agents” section of these guidelines

Minimum Analgesia Requirements for Mammals

Subcutaneous wounding, implantations or procedures without incising through muscle wall:
- NSAIDS
- Analgesia should be provided for a minimum of 24 hours post-op
Incisions into retro-peritoneal or abdominal cavity or the muscle wall:
- NSAIDS and/or Opioids
- Analgesia should be provided for a minimum of 48 hours post-op
Incisions into thoracic cavity through the muscle wall:
- Opioids
- Analgesia should be provided for a minimum of 48 hours post-op
Craniotomy
- NSAIDS and/or Opioids
- Analgesia should be provided for a minimum of 48 hours post-op

Local Anesthesia Along Intended Incisions (Line Blocks)

Table: Formulary for rats and mice

Local Anesthetic	Dose	Application	Notes
Lidocaine	Dilute to 0.5%, do not exceed 7mg/kg total dose; Incisional line block	Inject locally before surgical incision	Faster onset than bupivacaine (2-3 minutes after injection) but short (<1hour) duration of action
Bupivacaine	Dilute to .25%, do not exceed 8mg/kg total dose; incisional line block	Inject locally before surgical incision	Slower onset than lidocaine (20+ minutes) but longer (4-8 hour) duration of action
0.5% Lidocaine/0.25% Bupivacaine mixture	See formulation below; do not exceed maximum doses	Inject locally before surgical incision	Best option – rapid action of lidocaine with prolonged action of bupivacaine

Dilutions:

Lidocaine
Dilute the 2% (20 mg/ml) Lidocaine 1:4 to get final concentration of 0.5% (5 mg/ml)
- Example: 0.5 mL of 2% lidocaine + 1.5 mL sterile saline
- Label with drug, concentration, and expiration date
- See “IACUC Guidelines: Use of Drugs and Chemicals in Laboratory Animals” for further details (proper handling, expiration guidance, etc.)

Bupivacaine
Dilute the 0.5% (5 mg/ml) Bupivacaine 1:2 to get final concentration of 0.25%
- Example: 0.5 mL of 0.5% bupivacaine + 0.5 mL sterile saline
- Label with drug, concentration, and expiration date
- See “IACUC Guidelines: Use of Drugs and Chemicals in Laboratory Animals” for further details (proper handling, expiration guidance, etc.)

50/50 Mixture of Lidocaine/Bupivacaine
Dilute 2% (20 mg/ml) Lidocaine 1:4 and 0.5% (5mg/mL) Bupivacaine 1:2 in the same vial
- Example: 0.5 mL 2% lidocaine + 1 mL 0.5% bupivacaine + 0.5 mL sterile saline
- Label with drug, concentration, and expiration date
- See “IACUC Guidelines: Use of Drugs and Chemicals in Laboratory Animals” for further details (proper handling, expiration guidance, etc.)

Maximum Volumes

Weight of Mouse	Maximum Volume Diluted Lidocaine (0.5%) or Mixture Do not exceed:	Maximum Volume Diluted Bupivicaine (0.25%) Do not exceed:
25g	0.03ml	0.08ml
35g	0.05ml	0.11ml
45g	0.06ml	0.14ml
55g	0.07ml	0.17ml

Weight of Rat	Maximum Volume Diluted Lidocaine (0.5%) Do not exceed:	Maximum Volume Diluted Bupivicaine (0.25%) Do not exceed:
250g	0.35ml	0.8ml
350g	0.49ml	1.12ml
250g	0.63ml	1.44ml
550g	0.77ml	1.76ml

Line Block Procedure:

Determine maximum dose that can be used depending on weight of animal
Anesthetize the animal, and prepare skin for aseptic surgery
Inject local anesthetic into the subcutaneous space (“line block”) below the planned incision line, while withdrawing needle along incision line

Local Anesthetics should be used pre-operatively (before the first incision) and can be used in conjunction with opioid analgesics and/or NSAIDs for controlling moderate to severe pain. Intramuscular and intravenous injection of local anesthetics must be avoided. Systemic toxicity (seizures, heart rhythm disturbances and death) results from overdose or accidental intravenous injection.

Common Analgesic Agents

The following is a list of commonly used analgesic agents by species. This list is not inclusive; other analgesic agents may be listed and used in an Animal Protocol.

Other accepted resources for appropriate analgesics include the following formularies:

Plumb’s Veterinary Drug Handbook (Plumb)
Anesthesia and Analgesia in Laboratory Animals (ACLAM)
Formulary for Laboratory Animals (Hawk)
Exotic Animal Formulary (Carpenter & Marion)
Swine in the Laboratory (Swindle)
Sheep and Goat Medicine (Pew)

Appropriate analgesic drugs and dosage(s) should be determined in consultation with an OAR or IACUC veterinarian.

Mouse analgesics:

Class	Agent	Dose/Route/Frequency
Local	Bupivacaine 0.25% Lidocaine 0.5%	See above
NSAID	Flunixin meglumine	2.5 mg/kg SC every 12-24 hours
NSAID	Meloxicam /Meloxicam-SR*	1-5 mg/kg SC every 24 hours
NSAID	Carprofen	5 mg/kg SC every 24 hours
Opioid	Buprenorphine	0.05-2.5 mg/kg SC or IP every 6-8 hours
Opioid	Buprenorphine ER-LAB (sustained release)**	0.5-2.0 mg/kg SC every 48 hours
Opioid	Butorphanol	0.2-2 mg/kg SC or IP every 2-4 hours
Opioid	Oxymorphone	0.2-0.5 mg/kg SC every 6-12 hours

*Meloxicam-SR is a new product which claims 72 hours of duration in cats and dogs. Independent studies have not demonstrated efficacy beyond 24 hours post-administration in rodents. Use of this product in rodents is under continuing review by OAR veterinarians and requires close monitoring for signs of pain if expected effect is greater than 24 hours.

**Contact OAR Veterinarians for prescription and training

Rat analgesics:

Class	Agent	Dose/Route/Frequency
Local	Bupivacaine 0.25% Lidocaine 0.5%	See above
NSAID	Ketoprofen	5 mg/kg SC or PO every 24 hours
NSAID	Meloxicam / Meloxicam-SR*	1-2 mg/kg SC or PO every 24 hours
NSAID	Carprofen	5 mg/kg SC every 24 hours
Opioid	Buprenorphine	0.02-0.5 mg/kg SC, IV or IP every 6-8 hours
Opioid	Buprenorphine ER-LAB (sustained release)**	1.0-1.2 mg/kg SC every 48 hours
Opioid	Butorphanol	0.2-2 mg/kg SC or IP every 2-4 hours
Opioid	Oxymorphone	0.2-0.5 mg/kg SC every 6-12 hours

**Contact OAR Veterinarians for prescription and training

Rabbit Analgesics

Class	Agent	Dose/Route/Frequency
Local	Bupivacaine 0.25% Lidocaine 0.5%	Line block, consult with vet staff
NSAID	Carprofen	1-2.2 mg/kg PO every 12 hours
NSAID	Flunixin meglumine	1-2 mg/kg SC or IM every 12-24 hours
NSAID	Ketoprofen	3 mg/kg SC every 24 hours
NSAID	Meloxicam	0.2-0.6 mg/kg SC or PO every 24 hours
Opioid	Buprenorphine	0.01-0.05 mg/kg SC, IM or IV every 6-12 hours
Opioid	Buprenorphine ER (sustained release)**	0.1-0.3 mg/kg SC every 48-72 hours
Opioid	Butorphanol	0.1-1 mg/kg SC, IM or IV every 4-6 hours
Opioid	Oxymorphone	0.05-0.2 mg/kg SC or IM every 8-12hours

**Contact OAR Veterinarians for prescription and training

Pig Analgesics

Class	Agent	Dose/Route/Frequency
Local	Bupivacaine 0.25% Lidocaine 0.5%	Line block, consult with vet staff
NSAID	Carprofen	2-3 mg/kg IM, SC or PO every 24 hours
NSAID	Flunixin meglumine	1-4 mg/kg IM or SC every 12-24 hours
NSAID	Ketoprofen	1-3 mg/kg IM, SC or PO every 24 hours
NSAID	Meloxicam	0.4 mg/kg SC every 24 hours
NSAID	Phenylbutazone	4-8 mg/kg PO every 12 hours
Opioid	Buprenorphine	0.005-0.1 mg/kg IM, SC or IV every 8-12 hours 0.005-0.01 recommended for augmenting anesthesia; 0.01-0.1 recommended for post-operative pain control
Opioid	Buprenorphine ER (sustained release)**	0.12-0.2 mg/kg SC every 48-72 hours
Opioid	Butorphanol	0.1-0.3 mg/kg IM, SC or IV every 8-12 hours
Opioid	Oxymorphone	0.15 mg/kg IM or SC every 4 hours

Sheep Analgesics

Class	Agent	Dose/Route/Frequency
Local	Bupivacaine 0.25% Lidocaine 0.5%	Line block, consult with vet staff
NSAID	Carprofen	4 mg/kg SC every 24 hours
NSAID	Flunixin meglumine	1-2 mg/kg IM, IV or PO every 12-24 hours
Opioid	Ketoprofen	2-3 mg/kg IM, IV or PO every 24 hours
Opioid	Phenylbutazone	2-6 mg/kg IV or PO every 12 hours
Opioid	Buprenorphine ER (sustained release)**	0.05-0.3 mg/kg SC or IM every 48-72 hours
Opioid	Buprenorphine	0.005-0.01 mg/kg IM every 4-6 hours
Opioid	Butorphanol	0.5 mg/kg SC every 2-3 hours

**Contact OAR Veterinarians for prescription and training

Ferret Analgesics

Class	Agent	Dose/Route/Frequency
Local	Bupivacaine 0.25% Lidocaine 0.5%	Line block, consult with vet staff
NSAID	Carprofen	1 mg/kg PO every 12-24 hours
NSAID	Flunixin meglumine	0.3-2 mg/kg SC every 12-24 hours
NSAID	Ketoprofen	1 mg/kg PO, SC or IM every 24 hours
Opioid	Buprenorphine	0.01-0.03 mg/kg SC, IM or IV every 8-12 hours
Opioid	Butorphanol	0.05-0.5 mg/kg SC, IM or IV every 8-12 hours
Opioid	Oxymorphone	0.05-0.2 mg/kg SC, IM or IV every 8-12 hours

Aquatic Species:

There are currently no pharmacokinetically based recommendations regarding efficacious drug dosing of analgesics that can be safely administered to Xenopus frogs, Danio fish, or many other aquatic animals. Limited lethality data suggest narrow safety indices for semi-terrestrial species such as the bullfrog. In fully aquatic species, analgesic agents with sedating qualities (e.g. opioids) carry the risk of drowning due to over sedation. Analgesic drugs and doses should be chosen and used very carefully. Consultation with an IACUC or OAR veterinarian prior to administration of analgesic agents and doses is required.

Some published analgesic doses for various amphibian species include:

Class	Agent	Dose/Route/Frequency
NSAID	Flunixin meglumine	25 mg/kg intraceolomic (q24-48 hours)
Opioid	Buprenorphine	14 mg/kg into dorsal lymph sac (duration variable) OR 38 mg/kg SQ (duration >4 hours in leopard frogs)
Opioid	Butorphanol	25 mg/kg intraceolomic q12 hours
Alpha agonist	Dexmedetomidine	120 mg/kg dorsal lymph sac q24 hours
Alpha agonist	Xylazine	10 mg/kg intracoelomic q12-24 hours

Non-pharmacologic methods of pain management

When pharmacological intervention (i.e. analgesic agents) is not possible or in addition to pharmacological intervention, these methods can be employed to decrease pain:

Skilled surgeon (reduce unintentional surgical trauma)
Acclimation of animals prior to surgery
Enhance environment to minimize stress (soft bedding, easy food access, soft food, warm temperature, decrease human traffic, decrease noise)
Fluid therapy to sustain hydration

Last Reviewed by the IACUC 7/17/2023