20 Aug 2018
Elisabetta Mancinelli
Job Title
Figure 1. A rabbit in pain may show non-specific signs. In some cases, the animal may show reluctance to move, and its appearance and posture may be abnormal.
In an issue of Veterinary Clinics of North America: Exotic Animal Practice, Flecknell (2018) discussed the effective use of analgesics in small mammals.
This is an important topic, as managing pain effectively in these species is challenging and requires pain intensity to be assessed. If pain assessment tools are largely used for other species, they are still in an early stage of development for small mammals. Despite the fact mechanisms of nociception and pain are similar for all mammals commonly presented to a veterinary practice, pain detection and assessment remains challenging in species such as rabbits and rodents.
If one fails to appreciate and recognise normal behaviour; habits (such as being nocturnal and prey species with the tendency to freeze in the presence of an observer); and general appearance of small rodents, ferrets, and rabbits, signs associated with pain may be overlooked. This results in the fact an appropriate analgesic plan cannot be established nor adjusted to suit the need of each individual.
A validated system to recognise pain and evaluate the efficacy of analgesic drugs administered would be helpful, as parameters used may fail to identify pain at an early stage, fail to indicate pain intensity and result in unalleviated pain for some time before clinical signs become apparent (Dunbar et al, 2016). However, assessment of specific behaviours and use of grimace scales to assess facial expression can be used in many of these species to overcome these difficulties and help make clinical decisions.
Observing spontaneous behaviour in a veterinary practice setting can be challenging, as the smells, sounds and sights of other patients, which may be predators of small mammals, may alter or even result in suppression of all behaviours. The initial assessment should be made, if at all possible, without disturbing the animal, and in a quiet and predator-free area free from all clues, including smells, sights and sounds.
Signs of pain may be non-specific and indication of an underlying health issue. Nevertheless, these signs are useful when examination suggests presence of pain – due to otitis, dental disease or arthritis, for example. They can also be helpful when assessing animals after surgical procedures when some pain is expected and inevitable. The animal’s appearance and posture (such as hunched) may be abnormal (Figures 1 and 2). Its coat may be unkempt and ruffled because of a lack of grooming and have the presence of piloerection.
Rats may have a red to blackish discharge around their eyes and nose, due to a buildup of secretions from their harderian glands (chromodacryorrhea). This buildup of material is a non-specific sign of disease, pain and other stress. It is important to remember freezing or hiding may be a normal response to an animal in pain or feeling threatened. However, a normal inquisitive and exploring behaviour may still be seen during these preliminary observations. The animal should then be examined more closely.
Abnormal gait and posture or signs of aggression may be seen. When handled, rather than attempting to escape, animals in pain may be apathetic or aggressive and bite.
When examining an animal, it may respond to manipulation or palpation of a painful area by vocalising or trying to bite. Remember, some mammals, such as guinea pigs, tend to vocalise loudly even if not in pain, and may respond to any manipulation by tensing its muscles and remaining immobile.
Pain scales, based on behavioural changes considered reliable indicators of pain, have been validated in dogs and cats, greatly improving the management of pain in these species. Similar scales have been developed for some small mammal species and rabbits, but are still in early stages. Nevertheless, pain with a visceral component – for example, after abdominal surgery or orchiectomy – often produces some characteristic behaviours in rats, mice, rabbits, and guinea pigs (Roughan and Flecknell, 2004; Wright-Williams et al, 2013; Leach et al, 2009a; 2009b; Ellen et al, 2016).
Flecknell (2018) suggested, given the shared characteristics of these behaviours, it is probable similar behaviours may be of value in assessing pain in other, less familiar species. Contraction of the abdominal muscles producing a hollowed-out appearance to the flanks, pressing of the abdomen on to the ground, back arching, staggering when performing normal behaviours and teeth grinding may be more specific signs of pain in some small mammal species. These behaviours may be seen frequently with moderate to severe pain (for example, 4 to 5 abnormal behaviours in 5 to 10-minute period in rats).
Rabbits may show a similar frequency, but may only do so if observed remotely. Even well-socialised rabbits, with a familiar observer, may reduce the incidence of these behaviours. Guinea pigs are even less demonstrative, and may require a prolonged period of observation or use of remote monitoring, which is usually impractical in a busy practice. Recording food and water intake is the simplest way of following an animal’s progress after surgery or during treatment of any disease condition.
In addition, using facial expressions and possibly the assessment of highly motivated behaviours (such as nest building or burrowing in mice and rats) may be more useful in clinical settings.
Facial grimace scoring systems (using facial expressions to assess pain) have been developed in rabbits, rats and mice to evaluate the degree of pain (Keating et al, 2012; Leach et al, 2011; 2012; Langford et al, 2010; Matsumiya et al, 2012; Sotocinal et al, 2011).
These systems seem to better correlate to clinical postoperative pain and similar approaches may be applicable in a wide range of species (Descovich et al, 2017), but care must be used because other factors can also result in animals showing the same facial expressions (Defensor et al, 2012). Facial expression may also be less susceptible to changing as a result of the non-specific effects of analgesics. Using grimace scales, in combination with other indicators, may provide the best means of assessing pain in many species.
It is exceptionally important to become familiar with normal behaviour patterns of rabbits and small mammals, as careful observation of these patterns and their changes facilitates detection of abnormalities. Many of the signs of pain are non-specific and can occur in response to non-painful stimuli as well.
Furthermore, history and clinical findings will need to be assessed for each individual alongside their behaviour and general appearance. However, it is also important to appreciate observation of normal behaviours and activity level, as well as pain assessment, takes time. This, coupled with the lack of familiarity vets have with many species, makes adequate pain assessment more challenging. Owners may be a valuable asset in these cases (Flecknell, 2018).
Flecknell (2018) stressed a similar approach to preventive analgesia widely recommended in larger species should be used in small mammals. Furthermore, effective pain relief after surgery should be considered part of an integrated approach to perioperative care. Distress and discomfort should also be alleviated as extensive evidence exists that, in people, stress and anxiety may increase the degree of pain experienced and the need for pain relief.
The choice of the most appropriate analgesic drug to use, its dose and frequency of administration is critical in species such as rabbits and rodents. However, other factors should be considered to try to minimise postoperative pain and ensure an uncomplicated recovery from surgery – such as careful surgical technique, gentle tissue handling, provision of appropriate nutritional and fluid support, adequate nursing care in a stress and predator-free environment, and avoidance of hypothermia during and following surgery.
A range of analgesic drugs is available for use, either alone or in combination, in rabbits and other small mammal species, such as NSAIDs, opioids and local anaesthetics.
Many of these species (such as rats and mice) are often used as laboratory models in studies regarding safety and efficacy of analgesic agents. Therefore, the number of relative publications found in scientific journals is enormous.
If extensive data is available for rats and mice, less information concerning rabbits, guinea pigs, hamsters and gerbils exists. No data of this type exists for other small mammals, such as chinchillas or chipmunks.
The spread of these animals in the pet industry has also lead to an increase in the number of publications dedicated to exotic companion mammal species. However, a small part of this body of literature is still composed of properly designed studies (Jekl et al, 2017). The large amount of information available often leads to extrapolation of dose rates from a variety of different sources.
Furthermore, the tests performed in lab settings on healthy, pathogen-free animals kept in controlled conditions are not always directly relevant to the types of pain seen in veterinary practice, or directly applicable to pet individuals, often unhealthy or kept in suboptimal situations.
Dose rates need to be estimated very carefully in clinical practice. Further consideration needs to be given to the fact few studies exist on the efficacy of analgesics in clinically relevant situations and information available has often been obtained from clinical experience, and often recommended based on dose rates initially estimated by direct extrapolation from other species.
When applied in clinical situations and found to be at least safe, these dose rates become established in textbooks and review articles, even if efficacy has not been evaluated reliably. It is, therefore, important to continue to review analgesic use because recommendations change more frequently than for the more familiar companion animal species (Flecknell, 2018).
Most published data available for meloxicam and carprofen show a marked species variation in NSAIDs efficacy between species with high dose rates often required in mice compared to rats. In rabbits, high doses of meloxicam are needed for postoperative analgesia, and these need to be combined with local anaesthesia or opioids for effective pain relief (Leach 2009b; Cooper et al, 2009; Goldschlager et al, 2013).
This highlights the care needed when extrapolating between species, without means of evaluating clinical efficacy. Several studies have been published on the use of meloxicam in rabbits and should be reviewed (Turner et al, 2006a; 2006b; Karachalios et al, 2007; Leach et al, 2009b; Carpenter et al, 2009; Cooper et al, 2009; Fredholm et al, 2013; Goldschlager et al, 2013; Eshar and Weese, 2014; Delk et al, 2014; Khan and Rampal, 2014).
Buprenorphine is probably one of the opioid agents most extensively used in small mammals as the degree of analgesia provided is generally sufficient to control most postsurgical-related pain. Higher doses generally provide a longer duration of action (range four to eight hours at commonly used dosages, depending on species; Roughan and Flecknell, 2002; Gades et al, 2000; Jirkof et al, 2015; Sauer et al, 2016).
Patch formulations of opioids (such as fentanyl) have been used in rabbits, with reports indicating effective plasma concentrations could be produced, but this was complicated by rapid hair regrowth. Using depilating agents resulted in rapid fentanyl absorption and signs of sedation, but with no demonstration of efficacy (Foley et al, 2001).
The reported reduction in gut motility caused by opioids in rabbits, guinea pigs and chinchillas does not seem to be a problem in clinical practice. Any side effect produced by opioid administration is likely to be minimal compared with the effects of surgery in producing ileus. Furthermore, provision of effective pain relief encourages the animals to resume feeding rapidly, helps re-establish normal gut function and speeds up recovery.
Plasma concentrations of tramadol were found to be variable in the rabbit after oral administration (Souza and Cox, 2008). As its clinical efficacy remains unclear, tramadol should be used in rabbits only when other agents are considered unsuitable or as an oral formulation to provide more prolonged analgesia in animals once home, perhaps in combination with an NSAID when more potent analgesia is required (Flecknell, 2018).
The use of local anaesthetics in small mammals has long been neglected due to misinterpretation of some early studies, resulting in textbooks stating these agents were highly toxic in rodents.
Clinical experience and laboratory studies (data are available for small rodents and, although fewer, rabbits and guinea pigs) have indicated the agents can all be used safely and effectively, and be administered as splash blocks, local infiltration, blocking specific sensory nerves and the epidural or intrathecal route. When using these agents in small mammals, the total safe dosage (and additive effects if more agents are used in combination) should be calculated and prepared for use. In small patients, the volume of agent can be increased by dilution, but this may reduce its duration of action (Flecknell, 2018).
Continued provision of effective pain relief is also required once the animal is back in its home environment. In laboratory settings, one approach involves the addition of analgesics to the drinking water. However, several significant problems are associated with this method, which may result in a variable dose being administered. In summary, it is better to provide the owners with a syringe and a small, but precise, quantity of oral medication.
Clinical judgement is essential when choosing an appropriate analgesic regimen for a particular patient. It is, therefore, important to attempt to assess pain (for example, acute or chronic) to evaluate the efficacy of the analgesic plan administered.
However, a typical regimen likely to provide effective analgesia after ovariohysterectomy or similar surgery in rabbits or mammary tumour removal in rats may include buprenorphine preoperatively, meloxicam or carprofen during recovery from anaesthesia, followed by repeated doses of the NSAID by mouth for at least one to two days following surgery. If needed, the buprenorphine dosing could be repeated five to seven hours after recovery. Adding a local anaesthetic block seems particularly effective during procedures such as orchiectomy, where infiltration of the surgical site is easy. To provide both immediate local anaesthetic effects and some postsurgical analgesia, lidocaine may be combined with bupivacaine.
As in other species, pain should be managed effectively as part of the treatment plan for the condition affecting the patient. Use of an analgesic should always be considered, particularly when procedures likely to exacerbate the degree of pain are undertaken.
