Analgesic Drugs

Analgesic Drugs - Rats & Mice

The Use of Analgesics in Rats and Mice

Rationale

The Animal Welfare Act (AWA) defines a painful procedure as any procedure that would reasonably be expected to cause more than slight or momentary pain and/or distress in a human being to which that procedure is applied. Emory University’s Institutional Animal Care and Use Committee adopts this definition for all species and expects analgesics to be used to alleviate pain unless there is scientific justification to do otherwise.

In addition, well-established studies have shown repeatedly that effective analgesia enhances locomotion, increases appetite, and reduces the time of postoperative recovery for humans, rodents, rabbits, which are particularly sensitive to pain and inflammation, and other species. As a general rule, for maximal effectiveness, analgesics should be first administered before the animal is fully recovered from anesthesia and should be continued for the next 48-72 hours. However, as little as a single post-operative dose, in many circumstances, is sufficient to dramatically and positively influence recovery.

Mechanism of Action

Analgesics can act through several mechanisms. Centrally-acting agents, such as morphine, meperidine, codeine, nalbuphine and buprenorphine, interact with the endogenous opioid systems in the CNS. Substances that act locally at the nociceptor, such as local anesthetics, antihistamines, and alpha-2 adrenoreceptor agonists (i.e. xylazine, clonidine, metomidate), block nerve impulses. Nonsteroidal anti-inflammatory drugs (NSAID), such as aspirin, flunixin meglumine and acetaminophen, inhibit the production of the chemical mediators that activate peripheral nociceptors.

Nonsteriodal Anti-Inflammatory Drugs

NSAIDs are sufficiently potent to treat musculoskeletal, incisional, and acute, mild visceral pain. They inhibit the production of metabolic products of arachidonic acid (prostaglandins, prostacyclin) which are potent chemical mediators of inflammation that activate peripheral nociceptors. Because of different sites of action, these agents are synergistic with opioids. However, combinations of NSAIDs should not be used together as they may cause gastritis/gastric ulceration, or renal failure. Platelet inhibition is also a risk especially with agents with cyclooxygenase I activity. Carprofen (Zenecarp) has low cyclooxygenase 1 inhibitory effects and a low potential for renal or gastric toxicity (safer than flunixin). It is very effective when combined with opioids or buprenorphine and has a 24-48 hour duration of efficacy in most species.

Opioids

For the control of acute or chronic visceral pain, opioids are the most powerful and effective analgesics. Bradycardia, respiratory depression, excessive sedation, nausea, ileus and pica may be side effects. Opioid agonist-antagonists, such as buprenorphine, have minimal side effects. Opioids and opioid agonist-antagonists may increase CSF pressure and should be used with caution in craniotomy cases. In addition, the use of most of these agents is strictly controlled by the federal government requiring specialized licensure and the need to record every drop used. The use of traditional, parenterally-administered opioid analgesics such as morphine are generally impractical in rodents because of their high metabolic rates which necessitates intensive dosing schedules to maintain therapeutic blood concentrations. Buprenorphine is the most commonly used opoid in rodents due to its longer durations of action witn minimal side effects. Sustained release buprenorphine formulations are now available that release the drug over a 72-hour period after injection. The administration of NSAIDS concomitantly with opioids may allow the effective use of lower doses of opioids with fewer side effects and adequate pain management.