Analgesia Guidelines
Find recommended analgesics by species, as well as general information about analgesia for rodents.
Analgesia relieves pain without loss of consciousness.
Pain is difficult to assess in animals, so indirect signs are often used to identify pain, including abnormal posturing, vocalization, decreased appetite, and self-mutilation.
Because of the difficulty in determining when an animal is in pain, animal welfare regulations require providing analgesia whenever a procedure is being performed or a condition is present that is likely to cause pain. In the absence of evidence to the contrary, it is assumed that something that is painful in humans will also be painful in animals.
Analgesia is best provided pre-emptively, or prior to the painful procedure, rather than after observing clinical signs of pain. Systemic and/or local analgesics may also reduce anesthetic requirements. Several viable options exist to relieve pain in laboratory animals.
Opioids: Buprenorphine, fentanyl
Opioids exert their effects on the opiate receptors in the central nervous system. Opioids are effective for acute, deep, or visceral pain.
The most commonly used opioid in laboratory animal medicine is buprenorphine, which manages mild to moderate pain. Potential side effects include respiratory depression, nausea, vomiting, pica (rats), and constipation. Sustained-release buprenorphine has been associated with dermatitis and ulceration at the site of administration in rats and mice.
All opiates are controlled substances, and their use requires special record keeping.
Non-steroidal anti-inflammatory drugs (NSAIDs): Carprofen, meloxicam, ketoprofen
Generally, the NSAID classification applies to drugs that inhibit one or more steps in the metabolism of arachidonic acid (AA). NSAIDs act primarily to reduce the biosynthesis of prostaglandins by inhibiting cyclooxygenase (COX).
NSAIDs are effective for pain associated with inflammation. On their own, NSAIDs are effective against pain of mild to moderate intensity.
Potential side effects include gastric or intestinal ulceration, disturbance of platelet function, and changes in renal function.
Local analgesia: Lidocaine, bupivacaine
Local analgesics may be administered by several techniques. Anesthetic effects are seen within 15 minutes of administration and may last from 45 minutes to several hours, depending on the drug used.
- Infiltration or infusion: Injection beneath the skin and other tissue layers along the site of an incision before or after a procedure.
- Field block, ring block: Injection into soft tissues distant from the actual incision in a pattern that intersects the nerve supplying the surgical site.
- Nerve conduction block: Infusion of a small amount of drug or directly adjacent to the sheath of a nerve supplying the surgical site.
- Topical local anesthetics, such as lidocaine jelly, may be useful for some surgical wounds.
Note that the doses provided do not apply for epidural administration.
Rodents: General information about analgesia
Administration routes for rodents
Administration routes for rodents
Direct routes of administration (e.g., oral gavage or parenteral) are strongly recommended for accurate dosing.
Mild pain or discomfort:
For procedures that cause mild or momentary pain or discomfort, analgesics maybe given in the water. For procedures that cause a mild persistent pain or discomfort, analgesics in the water may be utilized post-operatively, provided that an initial analgesic dose is administered via a direct route during or immediately after the procedure.
Moderate to severe pain:
For procedures that cause moderate to severe pain, post-operative analgesics should be administered directly via parenteral injection or oral gavage. In most cases, a multi-modal regimen should be considered.
Sustained release (SR) formulations of opioid or non-steroidal anti-inflammatory drugs (NSAIDs) are available and may represent excellent options for decreasing stress associated with multiple injections.
Consult with your area veterinarian to develop an appropriate analgesic plan or for more information on acquiring sustained release products.
Administering analgesics via drinking water
Administering analgesics via drinking water
Analgesics may be administered via drinking waterfor procedures causing more than mild momentary pain/discomfort if the Institutional Animal Care and Use Committee (IACUC) protocol includes:
- A clearly stated scientific justification indicating why direct administration cannot be used for the study.
- A description of the methods used to ensure animals consume the appropriate amount of analgesic water and an outline of how clinical assessments of pain will be performed. It is the investigator’s responsibility, in consultation with the area veterinarian, to determine the best methods to accomplish these tasks. Following are example methods:
- Monitoring fluid intake: Measure the volume or weight of the water bottle to ensure an acceptable amount of fluid displacement has occurred within the daily time period. In addition, weigh each animal every day to ensure appropriate fluid and food consumption.
- Clinical assessment of pain: Include identifying signs such as hunched posture, decreased activity or hyperactivity, dehydration determined by a prolonged skin tent when scruffed, ruffled hair coat or lack of grooming, self-mutilation, altered mobility, decreased hindlimb-rearing behavior, decreased fecal output, or poor nest incorporation.
- A description of criteria for providing rescue analgesics (additional doses or routes of analgesia given) or euthanasia for any animals identified as having unexpected or unrelieved pain.
- An outline of procedures for replacing analgesic water when an empty water bottle is identified on weekends, nights, and holidays.
Lab personnel must:
- Provide water bottles containing analgesics at least 12-24 hours before the painful procedure. Rodents are neophobic, and they may initially decline to consume water that contains new substances.
- Document in post-operative records that a daily assessment for the presence or absence of signs of pain was performed.
- Maintain appropriate identification of cages receiving medicated water by properly labeling bottles and provide signage on the cage stating the analgesic used, the date the bottle was made, and the dose of the drug.
Examples of potentially painful procedures in rodents
Examples of potentially painful procedures in rodents
Mild, momentary pain or discomfort
- Percutaneous vascular catheter implantation
- Ear notch
- Superficial tumor inoculation (subcutaneous (SQ) or similar)
- Multiple injections
- Tail snipping (neonatal rodents)
- Embryo transfer (transvaginal)
Mild, persistent pain or discomfort
- Tail snipping (adult rodents)
- Subcutaneous pump or pellet implantation
Moderate pain
- Embryo transfer (surgical)
- Ovariectomy/Orchidectomy
- Tail amputation
- Craniotomy
- Minor laparotomy with minimal organ manipulation
Severe pain
- Orthopedic procedures
- Thoracotomy
- Organ transplant
- Major laparotomy with organ manipulation
- Burns
- Trauma models
Recommended analgesic protocols for rodents
Recommended analgesic protocols for rodents
Mild, momentary pain or discomfort
- Analgesia may not be indicated.
Mild, persistent pain or discomfort
- Use any one of the three types of analgesia: Local, opioid, or NSAID.
- Administer a single dose of injectable analgesia on the day of the procedure.
- Analgesia may be given in the water following the initial injection.
- Provide additional doses as needed based on pain evaluation.
Moderate pain
- Use a combination of at least two of the three types of analgesia. For example, NSAID + opioid or NSAID + local.
- Administer a single dose of injectable analgesia on the day of the procedure.
- Provide additional doses via injection or analgesia in drinking water for at least 1-2 days following the procedure.
- Provide additional or rescue analgesia doses as needed, based on clinical pain evaluation.
Severe pain
- Use all three types of analgesia.
- Where possible, pre-empt the painful event by starting NSAIDs and/or opioids in advance.
- Provide injectable analgesia for at least 3-5 days. Analgesia in the drinking water is not a reliable source.
Mice
Mice
Opioids
Buprenorphine-HCL
Dose: 0.05-0.1 mg/kg
Route: Subcutaneous (SQ), intraperitoneal (IP)
Frequency: Every 4-6 hours for the first 12 hours, and every 8-12 hours afterward. Dosing frequency may be decreased if using multi-modal analgesia consisting of opioid, NSAID, and local analgesia.
BuprenorphineSR™ (Sustained Release)
Dose: 2 mg/kg
Route: SQ
Frequency: Every 72 hours. Administer the first dose 2-4 hours prior to the painful procedure to ensure effective analgesia.
NSAIDs
Carprofen
Dose: 5 mg/kg
Route: SQ, IP
Frequency: Every 24 hours
Meloxicam
Dose: 1-2 mg/kg
Route: SQ, orally (PO)
Frequency: Every 24 hours
Ibuprofen*
Dose: 50-60 mg/kg/day – 10 ml Children’s Motrin in 500 ml water*
Route: PO
Frequency: Continuously in the water (change water every 3 days)
Ketoprofen
Dose: 5 mg/kg
Route: SQ
Frequency: Every 24 hours, for 3 days maximum
Local analgesia
Lidocaine
Dose: 4 mg/kg (0.4 mL/kg of a 1% solution)
Route: Local infiltration
Frequency: Do not exceed 7 mg/kg total dose
Bupivacaine
Dose: 1-2 mg/kg (0.4-0.8 mL/kg of a 0.25% solution)
Route: Local infiltration
Frequency: Do not exceed 6 mg/kg total dose
* All drinking water doses are approximations based on normal daily water consumption for a given species. A neophobic response has been documented when adding drugs to water of rodents, which can cause weight loss, but is usually temporary. The drug should be added to the water several days prior to the painful procedure, to allow rodents the opportunity to acclimate. Drugs delivered via drinking water should not be used as the sole source of analgesia for the first 24 hours after a painful procedure.
Rats
Rats
Opioids
Buprenorphine-HCL
Dose: 0.01-0.05 mg/kg
Route: Subcutaneous (SQ), intraperitoneal (IP)
Frequency: Every 4-6 hours for first 12 hours, and every 8-12 hours afterward. Frequency of dosing may be decreased if using multi-modal analgesia consisting of opioid, NSAID, and local analgesia.
BuprenorphineSR™ (Sustained Release)
Dose: 1.0-1.2 mg/kg
Route: SQ
Frequency: Every 48-72 hours
NSAIDS
Carprofen
Dose: 5 mg/kg
Route: SQ, IP
Frequency: Every 24 hours
Meloxicam
Dose: 1-2 mg/kg
Route: SQ, orally (PO)
Frequency: Every 24 hours
Ibuprofen*
Dose: 60-150 mg/kg/day – 25 ml Children’s Motrin in 475 ml water*
Route: PO
Frequency: Continuously in the water (change water every 3 days)
Ketoprofen**
Dose: 2.5-5 mg/kg
Route: SQ
Frequency: Every 24 hours, for 3 days maximum
Local analgesia
Lidocaine
Dose: 4 mg/kg (0.4 mL/kg of a 1% solution)
Route: Local infiltration
Frequency: Do not exceed 7 mg/kg total dose
Bupivacaine
Dose: 1-2 mg/kg (0.4-0.8 mL/kg of a 0.25% solution)
Route: Local infiltration
Frequency: Do not exceed 6 mg/kg total dose
* All drinking water doses are approximations based on normal daily water consumption for a given species. A neophobic response has been documented when adding drugs to water of rodents, which can cause weight loss, but is usually temporary. The drug should be added to the water several days prior to the painful procedure, to allow rodents the opportunity to acclimate. Drugs delivered via drinking water should not be used as the sole source of analgesia for the first 24 hours after a painful procedure.
** Ketoprofen should be used with caution in rats. Rats given ketoprofen may develop severe gastric ulcers. If used, provide moist food, and watch for side effects such as firm dark feces or a rat that is pale in color indicating possible ulcers. If seen, contact your area veterinarian.
Alternative NSAIDs such as carprofen or meloxicam are preferred.
Hamsters
Hamsters
Opioids
Buprenorphine-HCL (opioid)
Dose: 0.1-0.5 mg/kg
Route: Subcutaneous (SQ)
Frequency: Every 6-12 hours
NSAIDs
Carprofen
Dose: 5 mg/kg
Route: SQ
Frequency: Every 24 hours
Meloxicam
Dose: 1-2 mg/kg
Route: SQ, orally (PO)
Frequency: Every 24 hours
Ketoprofen
Dose: 5 mg/kg
Route: SQ
Frequency: Every 24 hours, for 3 days maximum
Local analgesia
Lidocaine
Dose: 4 mg/kg (0.4 mL/kg of a 1% solution)
Route: Local infiltration
Frequency: Do not exceed 7 mg/kg total dose
Bupivacaine
Dose: 1-2 mg/kg (0.4-0.8 mL/kg of a 0.25% solution)
Route: Local infiltration
Frequency: Do not exceed 6 mg/kg total dose
Guinea pigs
Guinea pigs
Opioids
Buprenorphine-HCL (opioid)
Dose: 0.05-0.1 mg/kg
Route: Subcutaneous (SQ)
Frequency: Every 6-12 hours
NSAIDs
Carprofen
Dose: 2-5 mg/kg
Route: SQ
Frequency: Every 12-24 hours
Meloxicam
Dose: 0.1-0.3 mg/kg
Route: SQ, PO
Frequency: Every 24 hours
Ibuprofen
Dose: 10 mg/kg
Route: PO
Frequency: Every 4 hours
Ketoprofen
Dose: 1-2 mg/kg
Route: SQ
Frequency: Every 24 hours, for 3 days maximum
Local analgesia
Lidocaine
Dose: 4 mg/kg (0.4 mL/kg of a 1% solution)
Route: Local infiltration
Frequency: Do not exceed 7 mg/kg total dose
Bupivacaine
Dose: 1-2 mg/kg (0.4-0.8 mL/kg of a 0.25% solution)
Route: Local infiltration
Frequency: Do not exceed 6 mg/kg total dose
Rabbits
Rabbits
Opioids
Buprenorphine-HCL
Dose: 0.01-0.05 mg/kg
Route: Subcutaneous (SQ), intramuscular (IM)
Frequency: Every 6-12 hours
Fentanyl
Dose: ½ of a 25 mcg/hr patch (do not cut – place surgical tape over ½ of patch)
Route: Trans-dermal patch
Frequency: Every 72 hours
NSAIDs
Carprofen
Dose: 2-4 mg/kg
Route: SQ, orally (PO)
Frequency: Every 24 hours
Meloxicam
Dose: 0.1-0.3 mg/kg
Route: SQ, PO
Frequency: Every 24 hours
Ibuprofen
Dose: 2-7.5 mg/kg
Route: PO
Frequency: Every 12-24 hours
Ketoprofen
Dose: 1-3 mg/kg
Route: IM
Frequency: Every 24 hours, for 3 days maximum
Local analgesia
Lidocaine
Dose: 4 mg/kg (0.4 mL/kg of a 1% solution)
Route: Local infiltration
Frequency: Do not exceed 10 mg/kg total dose
Bupivacaine
Dose: 1-2 mg/kg (0.4-0.8 mL/kg of a 0.25% solution)
Route: Local infiltration
Frequency: Do not exceed 4 mg/kg total dose
Pigs
Pigs
Opioids
Buprenorphine-HCL
Dose: 0.05-0.1 mg/kg
Route: Intramuscular (IM)
Frequency: Every 8-12 hours
BuprenorphineSR™ (Sustained Release)
Dose: 0.1-0.3 mg/kg
Route: Subcutaneous (SQ)
Frequency: Every 72 hours
Tramadol
Dose: 1-4 mg/kg
Route: Orally (PO)
Frequency: Every 8 hours
NSAIDs
Carprofen
Dose: 2-3 mg/kg
Route: SQ, PO
Frequency: Every 12-24 hours
Ketoprofen
Dose: 1-3 mg/kg
Route: IM
Frequency: Every 12-24 hours
Local analgesia
Lidocaine
Dose: 4 mg/kg (0.4 mL/kg of a 1% solution)
Route: Local infiltration
Frequency: Do not exceed 10 mg/kg total dose
Bupivacaine
Dose: 1-2 mg/kg (0.4-0.8 mL/kg of a 0.25% solution)
Route: Local infiltration
Frequency: Do not exceed 4 mg/kg total dose
Sheep
Sheep
Opioids
Buprenorphine-HCL
Dose: 0.005-0.01 mg/kg
Route: Intramuscular (IM)
Frequency: Every 4-6 hours
BuprenorphineSR™ (Sustained Release)
Dose: 0.1-0.3 mg/kg
Route: Subcutaneous (SQ)
Frequency: Every 72 hours
NSAIDs
Carprofen
Dose: 2-4 mg/kg
Route: SQ or intravenous (IV)
Frequency: Every 12-24 hours
Ketoprofen
Dose: 1-3 mg/kg
Route: IM
Frequency: Every 12-24 hours
Flunixin meglumine
Dose: 1.1-2.2 mg/kg
Route: IM or IV
Frequency: Every 24 hours
Local analgesia
Lidocaine
Dose: 4 mg/kg (0.4 mL/kg of a 1% solution)
Route: Local infiltration
Frequency: Do not exceed 10 mg/kg total dose
Bupivacaine
Dose: 1-2 mg/kg (0.4-0.8 mL/kg of a 0.25% solution)
Route: Local infiltration
Frequency: Do not exceed 4 mg/kg total dose
Dogs
Dogs
Opioids
Buprenorphine-HCL
Dose: 0.005-0.02 mg/kg
Route: Intramuscular (IM)
Frequency: Every 6-8 hours
BuprenorphineSR™ (Sustained Release)
Dose: 0.03-0.06 mg/kg
Route: Subcutaneous (SQ)
Frequency: Every 72 hours
Fentanyl
Dose: 1-5 ug/kg/h (following loading dose of 2 ug/kg)
Route: Trans-dermal patch
Frequency: Continuous
Tramadol
Dose: 2-5 mg/kg
Route: Orally (PO)
Frequency: Every 6-8 hours
NSAIDs
Carprofen
Dose: 2-4 mg/kg
Route: SQ, PO
Frequency: Every 12-24 hours
Meloxicam
Dose: 0.2 mg/kg day 1, 0.1 mg/kg afterwards
Route: SQ, PO
Frequency: Every 24 hours
Ketoprofen
Dose: 1-2 mg/kg
Route: SQ, IM
Frequency: Every 24 hours, for 3 days maximum
Local analgesia
Lidocaine
Dose: 4 mg/kg (0.4 mL/kg of a 1% solution)
Route: Local infiltration
Frequency: Do not exceed 10 mg/kg total dose
Bupivacaine
Dose: 1-2 mg/kg (0.4-0.8 mL/kg of a 0.25% solution)
Route: Local infiltration
Frequency: Do not exceed 4 mg/kg total dose
Cats
Cats
Opioids
Buprenorphine-HCL
Dose: 0.005-0.04 mg/kg
Route: Subcutaneous (SQ), intramuscular (IM), orally (PO)
Frequency: Every 6-8 hours
BuprenorphineSR™ (Sustained Release)
Dose: 0.12 mg/kg
Route: SQ
Frequency: Every 72 hours
Fentanyl
Dose: 12.5 mcg/hr
Route: Trans-dermal patch
Frequency: Continuous
Tramadol
Dose: 1-2 mg/kg
Route: PO
Frequency: Every 2-4 hours
NSAIDs
Carprofen
Dose: 1-2 mg/kg
Route: SQ, PO
Frequency: One time only
Meloxicam
Dose: 0.1-0.2 mg/kg PO, SQ day 1; 0.05 mg/kg PO afterwards
Route: PO, SQ on day 1 only; PO subsequent days
Frequency: Every 24 hours, for 3 days maximum
Ketoprofen
Dose: 1 mg/kg
Route: SQ
Frequency: Every 24 hours, for 3 days maximum
Local analgesia
Lidocaine
Dose: 2.5-3 mg/kg (0.3 mL/kg of a 1% solution)
Route: Local infiltration
Frequency: Do not exceed 10 mg/kg total dose
Bupivacaine
Dose: 1-2 mg/kg (0.4-0.8 mL/kg of a 0.25% solution)
Route: Local infiltration
Frequency: Do not exceed 4 mg/kg total dose
Rhesus macaques
Rhesus macaques
Opioids
Buprenorphine-HCL
Dose: 0.01-0.03 mg/kg
Route: Intramuscular (IM)
Frequency: Every 6-8 hours
Tramadol
Dose: 2-4 mg/kg
Route: Orally (PO)
Frequency: Every 12 hours
NSAIDs
Carprofen
Dose: 2-4 mg/kg
Route: Subcutaneous (SQ), PO
Frequency: Every 12-24 hours
Meloxicam
Dose: 0.2 mg/kg day 1, 0.1 mg/kg afterwards
Route: SQ, PO
Frequency: Every 24 hours
Ketoprofen
Dose: 1-2 mg/kg
Route: SQ, IM
Frequency: Every 12-24 hours, for 3 days maximum
Local analgesia
Lidocaine
Dose: 4 mg/kg (0.4 mL/kg of a 1% solution)
Route: Local infiltration
Frequency: Do not exceed 10 mg/kg total dose
Bupivacaine
Dose: 1-2 mg/kg (0.4-0.8 mL/kg of a 0.25% solution)
Route: Local infiltration
Frequency: Do not exceed 4 mg/kg total dose
References for these guidelines are available by request.