Introduction

Pain is present with many diseases as well as in association with surgical and traumatic conditions. The demonstration of pain is not always obvious; therefore, an animal should be assumed to be experiencing pain in any condition expected to produce pain in humans. The assessment and control of pain is an art as well as a science. Clinicians should keep in mind that the art of pain management is a continual learning experience, requiring assessment and therapeutic adjustment for individual animals even when they are undergoing similar surgical procedures. Therefore, standard or rule-of-thumb analgesic and anaesthetic protocols are not always appropriate.

If we accept that animals can experience pain, then how do we determine if a rabbit is or is not in pain? It is likely that the tolerance of pain by rabbits varies greatly from individual, as it does in other species. This coupled with exotic patients' innate ability to mask significant disease, and probably pain, make it difficult to assess pain. Compared with dogs and cats, very few investigations have been carried out on the assessment and alleviation of pain in rabbits. Most likely, as in cats, the mainstay of pain assessment in rabbits appears to be behavioural.

There are certain behaviours that are commonly seen in rabbits suffering acute trauma or postoperative pain. Such rabbits are often depressed, immobile, silent and appear distanced from their environment. They do not respond normally to petting or attention; rabbits tend to hide when experiencing pain. They may also hyperventilate. In the author's clinic, she has found that rabbits have a very similar response to pain as cats.

Multimodal Analgesia in Rabbits

The process of nociception and pain involves many steps and pathways, so one analgesic agent is unlikely to alleviate pain completely. An effective management plan includes drugs of different classes, each acting at a different part of the pathway; this is termed multimodal analgesia. For example, a rabbit can be premedicated with an opioid, which will modulate pain; ketamine can be used as a part of the induction protocol to reduce wind-up; a local anaesthetic block could be incorporated to inhibit transmission; and a non-steroidal antiinflammatory drug (NSAID) can be added pre- or postoperatively to alter transduction. This approach also allows smaller doses of each drug to be used as the effects are additive and may reduce any undesirable side effects from larger doses of individual drugs.

Constant rate infusions (CRIs) are delivered intravenously, frequently over a long period of time. CRIs have several advantages. They allow the drug to be titrated to effect, resulting in a reduction in the total amount of drug used, frequently result in fewer side effects, less 'rollercoaster' analgesia, fewer haemodynamic effects and are more cost effectiveness. Disadvantages include a slow rise in plasma concentrations to therapeutic levels, which is why a loading dose of the drug is frequently given prior to starting the CRI.

The easiest way to administer a CRI is via an automated mechanical pump system. In veterinary medicine, syringe pump systems are the most common delivery system and are mandatory for the small volumes used for rabbits. These small pumps utilise 1-60 ml syringes for delivery of the drug through an intravenous extension line. The syringe pump is advantageous because it allows very small volumes of drug to be delivered at a constant rate infusion.

Pain Management Options in the Rabbit

There is no doubt that rabbit pain management in clinical practice is presently inadequate. The rabbit has an undeserved reputation for adverse respiratory depression after opiate treatment. In the author's opinion, the rabbit becomes very comfortable and sleeps normally after administration of opioids postoperatively. Fear of these adverse effects has resulted in many rabbits not receiving analgesics after surgery or trauma.

Anaesthetic/Analgesic Drugs Used in Rabbits

The five major classes of analgesics employed for acute pain management are detailed below. All doses used by the author are given in Figure 1.

Figure 1. Tranquilliser/analgesics/anaesthetic drug doses for rabbits.

The following drug doses are those that are used by the author for use in the rabbit. Very few pharmacological studies have been performed with regard to the listed drugs in rabbit.

Opioids

Rabbits continue to have an undeserved reputation of having 'respiratory depression' after administration of opioid drugs. Resting very quietly without pain has been interpreted as respiratory depression. When used appropriately, opioids can be administered to rabbits and are safe and effective for alleviating pain. Opioids in general have a very wide margin of safety and excellent analgesic properties. In veterinary medicine, the most commonly used opioid CRIs are fentanyl, hydromorphone, morphine and butorphanol. Some animals may respond better to one opioid than another, depending on individual variability, breed and source of pain.

Non-Steroidal Antiinflammatory Drugs

NSAIDs are excellent agents for alleviation of acute postoperative and traumatic pain. As in other species, there are concerns about preoperative use of NSAIDs in rabbits. The main concern relates to inhibition of prostaglandin synthesis, which may lead to gastrointestinal erosion, impaired renal function and bleeding. The advantages of this category of drugs are their long duration of action and that no Drug Enforcement Administration (DEA) or controlled drug (in the UK) paperwork is required. In young rabbits with no evidence of renal disease, this group of drugs is a good choice. Meloxicam has recently become available as an injectable and oral form, and is the most commonly used NSAID in the rabbit because of its ideal dosing formulation. It has primary COX-2 inhibition. NSAIDs should not be used in animals with pre-existing renal disease, hypovolaemia, bleeding disorders or if severe surgical haemorrhage is anticipated. Flunixin meglumine is a NSAID and is a very potent inhibitor of cyclo-oxygenase.

Local Anesthetics

Local anaesthetic agents can be employed successfully in rabbits. The two most commonly used agents are lidocaine and bupivacaine. Suitable dosages and anticipated duration of action are shown in Figure 1.

Alpha-2 Agonists

Alpha-2 agonists, such as medetomidine, possess analgesic, sedation and muscle relaxant properties. These drugs are usually reserved for healthy animals because of the cardiopulmonary depression that accompanies their use. Microdose medetomidine preserves the blood pressure effects in healthy animals with good cardiac output, and provides good analgesic, sedation and muscle relaxation when used with a tranquilliser and opioid. These drugs have been used by the author in cardiovascularly stable rabbits at the low dose to help decrease the stress response.

NMDA Antagonists

The NMDA receptor plays an important role in the central sensitisation, and there is much interest in developing drugs that can inhibit this receptor. In veterinary medicine a commonly used NMDA antagonist is ketamine, which may be effective at preventing, or at least lessening, wind-up at subanaesthetic doses. When used with gaseous anaesthesia and opioids there is a reported opioid-sparing and gas anaesthetic-sparing effect seen. It is interesting to note that only minute amounts of ketamine need to be used via a CRI to have analgesic effects. Therefore, the cardiovascular effects that commonly occur with the anaesthetic doses of ketamine do not occur at the analgesic dose. The author uses microdose ketamine CRIs with opioid CRIs during surgery in the rabbit. When the CRIs are combined there is an overall gas anaesthetic-sparing effect.

Epidural Anaesthesia/ Analgesia in Rabbits

Epidural drugs achieve pain relief with less to no systemic effects, compared with drugs administered intramuscularly or intravenously. This factor is important in small mammals when the administered drug has negative side effects, such as cardiac and respiratory depression. Epidural drugs may decrease recovery time, which is always an advantage when working with rabbits. The improvement in recovery time occurs because of the decreased percentage of gaseous anaesthesia needed when used in conjunction with an epidural anaesthetic. In most small mammals, after epidural injection of lidocaine, analgesia develops within 10-15 minutes and lasts 60-90 minutes. Bupivacaine can provide up to 6-8 hours of surgical analgesia. Rabbits have been treated with lidocaine (1.5%) at 0.4 ml/kg. Morphine at 0.22 mg/kg that is administered into the epidural space provides prolonged postoperative analgesia for up to 24 hours.

Dental Nerve Blocks

This is a local block procedure that is used along with opioids and NSAIDs for dental procedures. The anaesthetic used is lidocaine (2%) mixed with bupivicaine (0.5%) in a 0.5 ml syringe administered with a 25 gauge needle. For each kilogram body weight mix 0.05 ml of lidocaine with 0.18 ml of bupivicaine and 0.27 ml of sterile water (can increase amount of sterile water to increase the total volume to be given). The total volume will be divided into the number of sites to block. The dental blocks are the infraorbital, mental, maxillary, mandibular and palatine nerve blocks.