Analgesia Recommendations for Laboratory Mice
Pain Levels and Examples
1. Momentary Pain
Description: Brief, transient pain that typically does not require analgesia.
Examples:
- Tail vein injections
- Ear tagging
- Subcutaneous implants with no undermining and no skin incision
2. Mild Pain
Description: Minor discomfort that minimally interferes with normal physiology and requires short-term analgesia).
Examples:
- Minor surgical procedures (e.g. small skin incisions, small biopsies, intracranial injections through small drill sites with no tissue undermining)
3. Moderate Pain
Description: Quantifiable pain that frequently interferes with normal physiology and requires effective analgesia to ensure animal welfare.
Examples:
- Subcutaneous implants with undermining (i.e. implants/pumps)
- Large biopsies
- Small incision abdominal surgeries (i.e. ovariectomies, castrations, kidney capsule implants)
- Orthopedic procedures (i.e., small joint defects)
- Intracranial injections requiring muscle or bone removal
4. Severe Pain
Description: Quantifiable intense pain that continually interferes with normal physiology and necessitates significant analgesic protocols.
Examples:
- Thoracotomy
- Large incision abdominal surgeries
- Major orthopedic surgeries (i.e. amputations)
Analgesia Standards
Multimodal Analgesia:
- Combination of opioids, NSAIDs, local anesthetics and supportive care for enhanced pain relief
1. Momentary Pain
- No analgesia typically required.
- Single dose NSAIDs may be used.
2. Mild Pain
- Single dose of either NSAIDs, local anesthetics, or opioids
- Local Anesthetics:
- Bupivacaine: Injected at incision site (≤ 2 mg/kg diluted appropriately).
- Opioids:
- Buprenorphine: 0.1-0.5 mg/kg subcutaneously may provide analgesia up to 4-6 hours.
- NSAIDs:
- Meloxicam: 10 mg/kg subcutaneously may provide analgesia up to 8-12 hours.
- Carprofen: 5 mg/kg subcutaneously may provide analgesia up to 12 hours; 20 mg/kg subcutaneously may provide analgesia up to 24 hours.
3. Moderate Pain
- Opioid and NSAID should be provided for at least 48 hours. Pain scoring is required to be performed and recorded for 24 hours past the end of the pain management protocol.
- Opioids:
- Buprenorphine: 0.1-0.5 mg/kg subcutaneously may provide analgesia up to 4-6 hours so dosing must be repeated before the end of the effective analgesic time period, or at the time that an animal begins to show any signs of pain.
- Extended-Release Buprenorphine:
- Ethiqa: 3.25 mg/kg subcutaneously may provide analgesia up to 72 hours.
- Buprenorphine Base ER Lab (compounded): 0.6 mg/kg subcutaneously may provide analgesia up to 48 hours.
- NSAIDs:
- Meloxicam: 10 mg/kg subcutaneously may provide analgesia up to 8-12 hours so dosing must be repeated before the end of the effective analgesic time period, or at the time that an animal begins to show any signs of pain.
- Carprofen: 5 mg/kg subcutaneously may provide analgesia up to12 hours so must be repeatedly administered; 20 mg/kg subcutaneously may provide analgesia up to 24 hours so dosing must be repeated before the end of the effective analgesic time period, or at the time that an animal begins to show any signs of pain.
4. Severe Pain
- MULTIMODAL ANALGESIA IS REQUIRED! Opioid and NSAID +/- local anesthetic (if appropriate) should be provided for 48-72 hours. Pain scoring is required to be performed and recorded for 24 hours past the end of the pain management protocol.
- Local Anesthetics:
- Bupivacaine: Injected at incision site (≤ 2 mg/kg diluted appropriately).
- Nocita: injected in all tissue layers at incision site (≤ 0.4 mL/kg diluted appropriately).
- Opioids:
- Buprenorphine: 0.1-0.5 mg/kg subcutaneously may provide analgesia up to 4-6 hours so dosing must be repeated before the end of the effective analgesic time period, or at the time that an animal begins to show any signs of pain.
- Extended-Release Buprenorphine:
- Ethiqa: 3.25 mg/kg subcutaneously may provide analgesia up to 72 hours.
- Buprenorphine Base ER Lab (compounded): 0.6 mg/kg subcutaneously may provide analgesia up to 48 hours and may need to be repeated.
- NSAIDs:
- Meloxicam: 10 mg/kg subcutaneously may provide analgesia up to 8-12 hours so dosing must be repeated before the end of the effective analgesic time period, or at the time that an animal begins to show any signs of pain.
- Carprofen: 5 mg/kg subcutaneously may provide analgesia for up to 12 hours so must be repeatedly administered;20 mg/kg subcutaneously may provide analgesia up to 24 hours so dosing must be repeated before the end of the effective analgesic time period, or at the time that an animal begins to show any signs of pain.
Additional Considerations
- Preemptive Analgesia: Administer analgesics before the onset of pain is required.
- Monitoring: Regularly assess pain levels and adjust analgesic protocols as needed (see below).
Any administration of substances must be documented. In addition, all monitoring (intra and post operatively) must be documented.
If a lab performs research with quantifiable outcomes that would be adversely affected by the standard pain protocols, robust justification (including references) for NOT following these requirements must be included in the animal use protocol.
Pain Scoring Using the Grimace Scale
The grimace scale is a method of assessing pain in laboratory rodents by observing changes in their facial expressions.
This website: https://nc3rs.org.uk/3rs-resources/grimace-scales, has posters of grimace scales in mice.
Key Facial Action Units for Mice:
- Orbital Tightening: Squinting or closing of the eyes.
- Nose Bulge: Bulging of the nose.
- Cheek Bulge: Bulging of the cheeks.
- Ear Position: Ears pulled back or flattened.
- Whisker Change: Whiskers pulled back or forward.
Scoring:
- 0: Feature is absent.
- 1: Feature is moderately present.
- 2: Feature is obviously present.
Application:
- Pre-Procedure: Observe and score the animal’s baseline facial expressions.
- Post-Procedure: Regularly observe and score the animal’s facial expressions to assess pain levels and adjust analgesic protocols as needed.
- Frequency of Grimace Scoring is based on pain severity.
- Mild: Immediately after the procedure, 1 check prior to end of day and 24 hours post procedure.
- Moderate: Immediately after the procedure,1 check prior to end of day then every 12 hours for 72 hours post procedure.
- Severe: Immediately after procedure, 1 check prior to end of day, then every 12 hours for 72-96 hours post procedure (24 hours past pain control).
Example:
- Orbital Tightening:
- 0: Eyes open normally.
- 1: Eyes partially closed.
- 2: Eyes fully closed.
If a lab wants to use a different method of evaluating pain, they need to provide scientific justification with references in the “Alternatives” section of the protocol.