Clinical Management of Pain in Rodents

Abstract

The use of effective regimens for mitigating pain remain underutilized in research rodents despite the general acceptance of both the ethical imperative and regulatory requirements intended to maximize animal welfare. Factors contributing to this gap between the need for and the actual use of analgesia include lack of sufficient evidence-based data on effective regimens, under-dosing due to labor required to dose analgesics at appropriate intervals, concerns that the use of analgesics may impact study outcomes, and beliefs that rodents recover quickly from invasive procedures and as such do not need analgesics. Fundamentally, any discussion of clinical management of pain in rodents must recognize that nociceptive pathways and pain signaling mechanisms are highly conserved across mammalian species, and that central processing of pain is largely equivalent in rodents and other larger research species such as dogs, cats, or primates. Other obstacles to effective pain management in rodents have been the lack of objective, science-driven data on pain assessment, and the availability of appropriate pharmacological tools for pain mitigation. To address this deficit, we have reviewed and summarized the available publications on pain management in rats, mice and guinea pigs. Different drug classes and specific pharmacokinetic profiles, recommended dosages, and routes of administration are discussed, and updated recommendations are provided. Nonpharmacologic tools for increasing the comfort and wellbeing of research animals are also discussed. The potential adverse effects of analgesics are also reviewed. While gaps still exist in our understanding of clinical pain management in rodents, effective pharmacologic and nonpharmacologic strategies are available that can and should be used to provide analgesia while minimizing adverse effects. The key to effective clinical management of pain is thoughtful planning that incorporates study needs and veterinary guidance, knowledge of the pharmacokinetics and mechanisms of action of drugs being considered, careful attention to individual differences, and establishing an institutional culture that commits to pain management for all species as a central component of animal welfare.

‘All Ears’: A Questionnaire of 1516 Owner Perceptions of the Mental Abilities of Pet Rabbits, Subsequent Resource Provision, and the Effect on Welfare

“…There is strong evidence to suggest vertebrates experience pain as of their anatomy and physiology, as well as their behavioral reactions to noxious stimuli [ 28 , 29 ]. Foley et al [ 29 ] state that small research animals (such as rabbits) undoubtedly centrally process pain equally to other large animals such as cats, dogs, and primates.…”

“…It has been shown across many laboratory animal pain studies that small mammal pain is often underestimated and under-dosed, leading to a significant welfare impact [ 29 , 30 , 31 ]. If trained veterinarians and experts in small laboratory mammal physiology are underestimating pain in their subjects, one can only imagine the deficit in knowledge and assessment in pain of the pet rabbits owned by the general public.…”

A Review of Pain Assessment Methods in Laboratory Rodents

“…51 in both human and veterinary medicine is to assess the response to analgesia (assuming that an effective dose of analgesic is administered). 40 Assessing animals before and after analgesic administration or comparing animals that received different agents or routes can often reveal whether the analgesic regimen is effective (Figure 8). 22 With this approach, it is important to understand the direction in which the chosen assessment parameter will change if pain is alleviated.…”

Cutaneous Radiation Injuries: Models, Assessment and Treatments

“…Use of a fentanyl patch should be considered. Because pain in animal models can be difficult to evaluate, a test or tool is needed to be better quantify the pain, especially in rodents (168). Euthanasia criteria must also be carefully designed and closely monitored.…”