Staff Training

The approach to rodent analgesia in laboratory animal medicine has undergone significant changes during the last decade,^1,2 and the need and benefits for analgesia in rodents has been clearly demonstrated. In spite of this, there are still personnel working with rodents who consider pain management to be unnecessary by making statement such as “rodents feel less pain than other mammals,” “pain is advantageous because it limits rodents' activity,” “analgesia conceals clinical deterioration,” or “alleviation of post-operative pain will result in the rodent injuring itself.” Obviously none of these statements are substantiated by scientific data. On the contrary, studies have shown that rodents are likely to experience pain at similar levels as other mammals. Pain may preclude rodents from being able to access food and water, and may lead to self-mutilation³— therefore, it must be addressed. Another stated justification for not using analgesia is that analgesics will adversely affect the results of an experiment.³ Analgesics do have an effect on a rodent’s physiology and behavior, however, this must be considered against the physiological effects of pain,which may include impairment of bowel motility and immune suppression.^4-9 Some may argue that the deleterious effects of pain far surpass any mild metabolic derangement caused by analgesia. The benefits of analgesia commonly surpass the rare and undesirable side effects which can arise from analgesic use. Because of the increased number of scientific studies regarding the detrimental side effects of pain, there is an increased use of appropriate analgesia in rodents.^1,2,10 Institutional Animal Care and Use Committees (IACUCs) must consider this argument and guard itself against “automatically” approving a surgical protocol without analgesics just because an investigator states that analgesics will interfere with data, even when references are provided.

Pain causes physiological and psychological changes in rodents such as ventilation, perfusion and cardiovascular abnormalities, increased metabolic demand, tissue catabolism, impaired immune function, increased risk of sepsis, delayed wound healing, a prolonged period of recovery, and abnormal behavior. ^4-9,11,12 Additionally, studies have demonstrated that a lack of control of acute pain increases the possibility of chronic pain.¹³ All of these have the potential to affect the results of an experiment, and increase morbidity and mortality.¹⁴ Beyond these reasons, we also have an ethical obligation to provide humane care and to comply with regulatory guidelines.^14,15

An understanding of the pharmacology, physiology, and specific applications of individual analgesics is vital in order to select the appropriate analgesic( s) for each case. The rodent’s health, age, strain, and the amount and duration of pain expected from a procedure are just a few of the considerations when choosing an analgesic protocol.^16-18 In some cases, like surgical procedures, the potential for pain is obvious. In other cases, the potential for pain is not as apparent. For example, more subtle sources of pain may occur from rodent models of arthritis, cancers (e.g. bone neoplasm), and infectious diseases (e.g. ulcerated lesions where pain can be chronic and subtle).^19-24 Every attempt should be made at treating pain preemptively, rather than waiting until a rodent is exhibiting signs of pain.²⁵ This prevents noxious stimuli from activating the central nervous system, which decreases the benefit and effectiveness effectiveness of the analgesic. Pre-emptive analgesia reduces peripheral inflammation, thereby decreasing the potential for central nervous system hypersensitivity. ²⁶ An analgesic protocol should include a multi-modal approach that incorporates analgesic agents from various classes such as opioids and nonsteroidal anti-inflammatory drugs (NSAIDS).^3,27 This approach allows analgesics to act at various points of the pain cascade, which leads to synergistic or additive activity and decreases overall drug toxicity. ^3,27 An optimal protocol of pain relief should include a preemptive and multi-modal approach with pre-, intra-, and post-procedural pain management.^3,25,27

Challenges of Pain Detection and Provision of Analgesia in Rodents
Detection of pain and the provision of analgesia in rodents is challenging because it is difficult to assess physiological and behavioral changes associated with pain in these animals. ^3,14,15,28 This is due to the fact that rodents are small, nocturnal animals, vocalize at ultrasonic frequencies and often mask signs of pain.^29-34 Therefore, pain detection in rodents utilizes subtle behavioral clues that alert personnel to their condition.^17,35-39 There is no universally accepted standard guideline or score sheet used to determine if a rodent is experiencing pain. ^15,35,38