Pain in animal experimentation is a major welfare issue, which must be minimized for ethical and legal reasons. Additionally, unrelieved pain may have substantial and poorly controllable effects.
Pain management includes the choice of anesthesia and analgesia agents, their dose, administration method, duration and frequency of treatment, and a pain-monitoring scheme for each individual animal.
An optimal analgesia protocol should relieve pain reliably and lack side effects that might hamper science and animal welfare. In case of surgical or painful procedures, preventive analgesia, defined as pre-, intra- and post-operative analgesia, must be planned to efficiently cover the temporal development of pain and the estimated intensity.
Pre-emptive analgesia is the administration of analgesia before the nociceptive insult to reduce sensitization of the pain pathways. This procedure is recommended when pain is expected during and after surgical or other invasive procedures because many anesthesia agents, such as isoflurane, do not induce analgesia. Pre-emptive analgesia has the potential to be more effective than a similar analgetic treatment initiated after surgery and to reduce the required analgesia dose.
Local anesthetic drugs can be used to limit or block activation of peripheral nociceptors, signal transduction along peripheral fibers of the nociceptive system, and processing of nociceptive signals at the level of the spinal cord.
Multimodal analgesia is a concept that involves different classes of analgetics and/or different sites of drug administration. Administering a combination of two or more drugs with well-established, possibly complementary, pharmacokinetics and mechanism of action has been shown to result in a synergistic or additive effect.
Refinement of administration
Desired and undesired effects of analgetics can largely depend on the administration mode. Additionally, the choice of administration route and interval can affect the animal’s well-being. The selection of the administration mode needs to weigh the respective advantages and disadvantages. The decision should consider the frequency of handling and restraint necessary for repeated administration on one hand and the uncertainties in sufficient dosing associated with self-administration on the other hand. Repeated injections or oral gavage of drugs require restraint of the animal, which can cause additional stress in small laboratory species and might increase existing pain.
To assure continuous and stress-free administration of analgesia, depot formulations of analgesics have been developed for different drugs. These formulations, due to their long release duration, significantly reduce the necessary frequency of drug administration. Respective formulations can on one hand limit the number of necessary injections and associated distress and can on the other hand result in a slow increase in plasma concentrations avoiding high peak concentrations.
Voluntary oral administration
Voluntary oral administration of analgesia is another promising approach that avoids the negative effects of handling. Several routes of oral administration have been described, such as mixing analgetics with flavored gelatin, Nutella, regular diet or (sweetened) drinking water.
These studies in mice and rats have shown that several analgetics are efficient when administered orally and voluntarily. Nevertheless, oral self-administration has been criticized as being less effective than subcutaneous treatment in rats. Reduced bioavailability caused by metabolizing of the drug before it reaches systemic circulation is a known obstacle in this administration route. Moreover, latency to ingestion as well as the total amount ingested by the animals, especially during the resting phase, is difficult to anticipate and is clearly variable for each individual. Thus, voluntary ingestion protocols might be applicable only when pain is mild, or in combination with drug injections, at least during the resting phase of rodents.
--PJirkof 09:01, 27 March 2020 (UTC)
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