STANDARD OPERATING PROCEDURE #102
RABBIT ANALGESIA
1. PURPOSE
The intent of this Standard Operating Procedure (SOP) is to describe methods of assessing pain in rabbits and mitigating
pain by administration of analgesic medications.
2. RESPONSIBILITY
Principal investigator (PI) and their research staff, veterinary care staff.
3. GENERAL CONSIDERATIONS
3.1. A procedure which would be expected to be painful if it were done on humans must be considered painful to the
animal.
3.2. When there is a question of whether or not a procedure is painful, the animal should receive the benefit of
analgesia.
3.3. Analgesia should be provided at an appropriate dose and frequency to control pain.
3.4. Any deviation from this procedure must be justified by the investigator and approved by the appropriate Facility
Animal Care Committee (FACC).
4. PAIN RECOGNITION AND ASSESSMENT
4.1. Adapt the frequency of observation to the invasiveness of the procedure (minimum once a day).
4.2. Start by observing the animal from a distance so the animal's behavior is not altered by the presence of the
observer. Then proceed to observe the animal more closely.
4.3. Look for any changes in the behavior. Report animals which appear to be in pain to the veterinary care staff.
4.4. Common clinical signs indicative of pain or distress include:
4.4.1. Avoidance, teeth grinding, vocalization and aggressiveness (mainly if the animal cannot escape)
4.4.2. Spontaneous activities are reduced. The animal is isolated from the social group
4.4.3. Altered gait
4.4.4. Hunched posture
4.4.5. Piloerection
4.4.6. Reduced grooming; dark-red stain around the eyes and at nostrils
4.4.7. Reduced appetite and subsequent weight loss
Note: The most reliable signs of pain and distress are the changes in behavior. This implies a good knowledge of
species and individual normal behavior by the observer.
SOP 102.02 – Rabbit Analgesia Page 1 of 6
4.5. Rabbit Grimace Scale (Keating et al. 2012)
The rabbit grimace scale is a standardized behavioral coding system that demonstrates facial expressions which
can be used to assess pain in the laboratory rabbit.
SOP 102.02 – Rabbit Analgesia Page 2 of 6
5. ANALGESIA PLAN
5.1. If possible, provide analgesia before the painful stimulus, as it is more effective in preventing pain (e.g. give
analgesic before surgery).
5.2. Try to use a combination of analgesics, which is often more effective than using a single agent.
For example, combination of buprenorphine, carprofen, and local infiltration of lidocaine/bupivacaine.
5.3. For surgical procedures, extend analgesia from pre-op to 72 hours post-op, unless otherwise specified in the
Animal Use protocol (AUP) and approved by the FACC.
6. LOCAL ANALGESIA
6.1. Infiltrate or apply local analgesic to areas where a painful stimulus may be induced. Repeat application of local
agent at specified intervals to maintain analgesia. In some cases a sedative is recommended when using local
analgesia.
Analgesic Dose Route Duration Note
Lidocaine < 2 mg/kg SC, 30–60 min. Use lidocaine HCl 2% (20mg/ml) injectable
Infiltration solution.
of surgical Because this drug is acidic, it is
wounds recommended to dilute it 3:1 with sodium
bicarbonate injectable solution (at 5 or
8.4%).
Dilution must be prepared immediately
before use and should not be stored. Diluted
solution is as effective but induction of
analgesia is slightly prolonged.
* Dilution with sodium bicarbonate is not
necessary if lidocaine is to be administered
to an anesthetized animal.
Bupivacaine < 2 mg/kg SC, 3–4 hr. Use bupivacaine HCl 0.50% (5mg/ml)
Infiltration injectable solution.
of surgical Same comment as for lidocaine.
wounds
* Lidocaine- < 2 mg/kg SC, 30min.-4 hr. Same comment as for lidocaine.
bupivacaine Infiltration Combining both drugs allows for rapid
mixture of surgical induction and prolonged effect.
wounds
Use a 1:1 mixture of lidocaine HCl 2%
(20mg/ml) injectable solution and
bupivacaine HCl 0.50% (5mg/ml) injectable
solution.
Discard mixture after 3 months.
EMLA cream Thick spread Topical 30–60 min. Shave or pluck the fur and apply a thick layer
of cream ideally 10 minutes before the
painful procedure.
Use only on intact skin.
*most commonly used
SOP 102.02 – Rabbit Analgesia Page 3 of 6
7. GENERAL ANALGESIA
Rabbit
Analgesic Dose Route Frequency Note
*Buprenorphine 0.05–0.1 Preferred: 8–12 hr. Mild to moderate pain.
mg/kg IM, IV, Controlled drug.
sublingual,
gingival
Other: SC
*Buprenorphine 0.12 mg/kg SC Once Buprenorphine SR (0.6mg/ml) is a sustained
Slow Release release buprenorphine product that has
(SR) been developed to provide 72 hours of
analgesia and is specifically designed for use
in rodents.
See administration instructions in section
7.2.
Controlled drug.
*Carprofen 4-5 mg/kg SC, PO 12–24 hr. Mild to moderate pain.
*Ketoprofen 2-5 mg/kg SC, IM, IV 12–24 hr. Mild to moderate pain.
*Meloxicam 0.3-0.5 mg/kg SC, PO 24 hr. Mild to moderate pain.
Fentanyl 25μg Patch Every 3 days, Moderate to severe pain.
starting 24h Controlled drug.
prior to
surgery
Morphine- 2 ml/kg/hr IV Constant rate Moderate to severe pain.
Lidocaine- infusion To a 500ml bag of fluids, add morphine
Ketamine 60mg, lidocaine 750mg and ketamine
Combination 150mg.
Controlled drugs.
*most commonly used
7.1. Administration of non-steroidal anti-inflammatory drugs (NSAIDs):
7.1.1. NSAIDs include carprofen, ketoprofen and meloxicam.
7.1.2. Ensure good water intake and monitor hydration status during the treatment period.
7.1.3. Suspend water restriction prior to administration of NSAIDs.
7.1.4. To minimize chances for adverse drug interactions, a washout period of 5-7 days is recommended before
switching between NSAIDs.
7.2. Administration instructions for buprenorphine slow release (SR):
7.2.1. Avoid contact with the skin to prevent the development of injection site reactions.
7.2.2. Draw up the buprenorphine SR with an 18g needle and change to a 23g needle prior to administration
7.2.3. Administer subcutaneously on back of neck between the shoulder blades, preferably while the animal is
anesthetized.
7.2.4. Administer slowly and finish injecting before the needle is pulled out.
7.2.5. Pinch the injection site for approximately 10 seconds after removing the needle
7.2.6. Do not combine the buprenorphine SR with any other drugs in the same syringe and do not attempt to dilute
the formulation.
SOP 102.02 – Rabbit Analgesia Page 4 of 6
8. REFERENCES
8.1. DiVincenti L Jr, Meirelles LA, Westcott RA. (2016). Safety and clinical effectiveness of a compounded sustained-
release formulation of buprenorphine for postoperative analgesia in New Zealand White rabbits. J Am Vet Med
Assoc. 2016 Apr 1;248(7):795-801.
8.2. Keating SCJ, Thomas AA, Flecknell PA, Leach MC (2012) Evaluation of EMLA Cream for Preventing Pain during
Tattooing of Rabbits: Changes in Physiological, Behavioural and Facial Expression Responses. PLoS ONE7(9):
e44437. https://doi.org/10.1371/journal.pone.0044437
SOP REVISION HISTORY
DATE NEW VERSION
2015.04.22 6.1 Use lidocaine HCl 2% (20mg/ml) injectable solution.
2015.04.22 6.1 Use bupivacaine HCl 0.50% (5mg/ml) injectable solution.
2015.04.22 6.1 Lidocaine-bupivacaine mixture: Discard mixture after 3 months.
7. Carprofen, ketoprofen and meloxicam:
2016.09.02 Ensure good water intake and monitor hydration status.
Suspend water restriction prior to administration.
2016.09.06 7. Buprenorphine route of administration: SC Preferred: IM, IV, sublingual, gingival Other: SC
7.1. Administration of non-steroidal anti-inflammatory drugs (NSAIDs):
7.1.1. NSAIDs include carprofen, ketoprofen and meloxicam.
2017.01.27 7.1.2. Ensure good water intake and monitor hydration status during the treatment period.
7.1.3. Suspend water restriction prior to administration of NSAIDs.
7.1.4. To minimize chances for adverse drug interactions, a washout period of 5-7 days is recommended before switching between NSAIDs.
2017.02.13 4.5 Grimace Scale Image replaced with NC3Rs poster image
Buprenorphine Slow Release (SR)
Dose: 0.12 mg/kg
Route of administration: SC
2017.10.17 Frequency: once
Note: Buprenorphine SR (0.6mg/ml) is a sustained release buprenorphine product that has been developed to provide 72 hours of analgesia and is specifically
designed for use in rodents. See administration instructions in section 7.2.
Controlled drug.
2018.10.12 7.2.6. Do not combine the buprenorphine SR with any other drugs in the same syringe and do not attempt to dilute the formulation.
2020.04.20 4.1. Adapt the frequency of observation to the protocol invasiveness of the procedure (minimum once a day).
2020.04.20 6.1 (Added routes for local analgesics)
2020.04.20 7.2.3. Administer subcutaneously on back of neck between the shoulder blades, preferably while the animal is anesthetized.
Approved by the McGill University Animal Care Committee Page 5 of 5
Written by: Jim Gourdon, Comparative Medicine & Animal Resources Centre SOP 102.02 – Rabbit Analgesia
Revised on (yyyy-mm-dd): 2020-04-20 Revision # 02 Effective date (yyyy-mm-dd):2008-09-01
