A broad range of conditions are associated with pain (e.g., acute or chronic inflammatory disease, neoplasm, trauma and iatrogenic causes such as surgery). Pain should not only be treated from a welfare and ethical point of view, but also from a medical perspective. It is well documented that poor pain management in the post-operative period has detrimental effects on the recovery, including wound healing and maximal restoration of function of the patient.

Managing pain in exotic companion mammals requires recognition of pain in these species. Once pain is recognized or suspected, this should be addressed by looking at all treatment options and taking unwanted side-effects into consideration.

Recognizing Pain

Pain is a highly subjective and individual experience and similar surgeries or disease states will be experienced differently by every individual. In addition, assessment of pain is difficult as many of the displayed signs are subtle. It is therefore best when behavioral changes are observed by people spending a fair amount of time with the animal. General behavioral characteristics frequently seen in animals with pain are: diminished general activity, altered posture, altered gait such as lameness, aggression in animals that are otherwise very friendly, apathy in animals that are otherwise fierce, vocalizations which differ in pitch and patter n from the normal interactive sounds, hiding in the back of the cage facing away from the observer, lack of grooming behavior resulting in ruffled and unkempt appearance of the hair coat, diminished food and water intake, bruxism especially in abdominal pain, and finally aversive response to external palpation of the animal. Prey species will attempt to hide pain to avoid predation.

Pharmacological Pain Management

Different classes of analgesic drugs can be used to prevent, eliminate or reduce the nociceptive input at different stages, forming the basis of a multimodal approach to pain management. The advantage of a multimodal approach is that different classes of analgesic drugs can have additive or synergistic effects, while the dose of the individual drugs can be lowered which in turn might reduce side effects and increase safety. Another important aspect to increase the efficacy of analgesic therapy is preemptive analgesia. It has been shown that previous experiences of pain can increase the aversiveness of subsequent painful events, pain might be treated best before it is actually present.

Therapeutics

The broad range of analgesic drugs used in more common companion species such as dogs and cats are also used in the exotic companion mammal species.

NSAIDs

NSAIDs exert their analgesic effects by inhibiting the enzymes cyclo-oxygenase 1 and 2 (COX-1 and COX-2). The COX enzymes are responsible for the production of prostaglandins which play an important role in inflammatory processes, but also in regulating renal and gastro-intestinal mucosal perfusion. In addition, they have an antipyretic activity.

Frequently, warnings are given for using NSAIDs for long-term treatment and in animals with hepatic, renal or gastro­ intestinal disorders. It is good to be cautious when using NSAIDs and make sure hydration of the patient is in order. Addressing chronic pain, however, may be more important than the perceived potential side effects. It is good to realize that people with, for instance, rheumatoid arthritis, use NSAIDs for years in a row, even when minor renal disease is present. When hepatic or renal failure is present, it has been advised in elderly to reduce the dose of pain medication to adjust for the impaired clearance of these drugs.

Meloxicam and carprofen, both potent COX-2 inhibitors, are currently the most frequently used NSAIDs in exotic companion mammal species.

Opioids and Tramadol

Opioids are used for the management of moderate to severe pain. They exert their analgesic effects by binding to the opioid µ-, κ- , and/or δ-opioid receptors. These drugs inhibit ascending nociceptive input, activate descending inhibitory pathways, and decrease neurotransmitter release. They might also be active peripherally in inflamed tissues. General side effects which can be seen after use of opioids include sedation, respiratory depression, and reduced gastrointestinal motility. It should be noted, however, that pain in itself can also result in respiratory depression, abnormal behavior, depressed food intake, and ileus. The use of opioids should therefore not be withheld in any animal which is experiencing pain.

Buprenorphine is a full µ-opioid receptor agonist with potent analgesic actions. It is thought to have less side effects, such as respiratory depression, nausea and dysphoria, compared to the other opioids. Profound sedation may be seen at doses greater than 20 µg/kg. The duration of action may vary from 6 to 12 hours. Before giving the next dose, it is advised to re-assess the animal to identify whether sedative effects or negative side effects are encountered. Based on these findings the subsequent dose can be adjusted.

Butorphanol also provides analgesia in several exotic companion mammal species. It is assumed that butorphanol has agonistic effects on µ-, δ- and κ-opioid receptor with the highest affinity for the κ-opioid receptor. Its clinical effects seem similar to buprenorphine. The duration of its analgesic actions, however, is significantly shorter. It also has a greater sedative effect and potentially results in more respiratory suppression.

Fentanyl, a short acting and very potent µ-opioid receptor agonist with potent analgesic actions can be used as a constant rate infusion (CRI). Fentanyl CRI is most often used during surgery and in the post-operative period. Respiratory depression is a potential serious side effect warranting frequent assessment of the ventilatory status of these patients.

Tramadol is not a typical opioid, with effects on the µ-opioid receptor, the serotonin-, the catecholamine- and the GABA-system. Palatability of tramadol is a significant problem in rabbits. In ferrets, palatability issues have not been reported. During a pharmacokinetic study in rabbits, a dose of 11 mg/kg did not result in plasma concentrations considered analgesic in people. No pharmacokinetic data are available in ferrets, but a dose of 10 mg/kg once daily has been suggested. Tramadol cannot be used in chinchillas as levels which may be analgesic will result in severe neurological signs.

Local Anesthetics and Locoregional Techniques

The use of local anesthetics - e.g., bupivacaine and lidocaine - can be very effective in preventing stimuli reaching the spinal cord and are very useful additions in a pain management plan. The good predictability of drug effect with respect to both desired and unwanted side effects of local anesthetics, together with insensitivity to species specific physiology makes locoregional techniques an excellent choice. Techniques that can be used are incisional line blocks, local infiltration, ring blocks, splash-blocks, topical application, conductive nerve block and epidural anesthesia. Care must be taken not to exceed maximum doses which need to be calculated beforehand, often requiring diluting the drug to obtain an adequate volume. Maximum doses are 1 to 2 mg/kg whereby it is important to realize that bupivacaine is twice as potent as lidocaine. Adding opioids such as morphine or buprenorphine to a local block can increase the duration of analgesia significantly.

Dental blocks are well described in rabbits and ferrets. These included the infraorbital nerve block, mental nerve block, mandibular nerve block and the maxillary nerve block. Intra-testicular blocks are also described. Allow at least 5 minutes for the local anesthetic to be fully effective.

Conclusion

Although a lot of data on clinical efficacy, pharmacokinetics and pharmacodynamics of analgesic drugs and specific behaviors related to pain are lacking in exotic companion mammal species, pain management does not really differ between species. Analgesic treatment is a dynamic, practical and subjective process. Therefore ‘clinical experience’ from colleagues and appropriate training in pain physiology and pain management is at least as valuable as ‘hard scientific’ data. People are therefore encouraged to maintain adequate record keeping and follow up, in addition to reporting on clinical experience with analgesics in rabbits and ferrets until more scientific evidence is available.

References

1.  Barter LS. Rabbit analgesia. Veterinary Clinics of North America: Exotic Animal Practice. 2011;14(1):93–104.

2.  van Oostrom H, Schoemaker NJ, Uilenreef JJ. Pain management in ferrets. Veterinary Clinics of North America: Exotic Animal Practice. 2011;14(1):105–116.

3.  Johnson AG, Day RO. The problems and pitfalls of NSAID therapy in the elderly (Part I). Drugs & Aging. 1991;1(2):130–143.