Management of post-operative pain after surgical procedures

Pain in laboratory animals is a major animal welfare problem that must be addressed if we are to apply Russell and Burch’s principle of refinement – ‘to reduce to an absolute minimum the pain and distress experienced by those animals that are used’ (in research procedures). In order to provide effective analgesia, it is essential that we have a good knowledge and understanding of animal pain. We need to know when pain might occur and how long it might last, and assess how well it responds to therapy. We also need to consider the advantages and the disadvantages of the various methods of managing pain, and how we can best apply these in different situations. If we are to manage pain relief optimally, and monitor the effects of our therapy, then we will need to recognise the presence of pain and assess its severity. When developing our understanding of this area, we will also need some information about the basic mechanisms involved in pain perception. More fundamentally, we must accept that pain occurs in animals – that it can result in suffering, in a similar way to pain in humans – and so  become convinced that its avoidance and alleviation need to be given a high priority.

Since pain is a subjective experience, it is doubtful that we will ever be able to demonstrate its presence in animals conclusively, but the growing body of evidence supporting conscious emotional states suggests we should assume a capacity for pain in animals. This view is reflected in the legislation that controls our treatment of animals. Irrespective of whether animals experience pain or simply respond to activation of sensory nerve (nociceptor) pathways, this process results in major physiological and pathophysiological changes. Consequently, pain or nociception will represent a source of uncontrolled variation in research and may introduce specific confounding factors in some studies. We can therefore advocate the control or elimination of both pain and nociception on both scientific and welfare grounds.

Although we would wish to alleviate pain either because of concerns for animal welfare or to reduce a potential confounding factor in a research project, a number of concerns have been advanced to justify withholding analgesics.

“Alleviation of post-operative pain will result in the animal injuring itself”

Pain has a protective function and is of value in warning of tissue damage in an individual. Pain arising from injured tissues often results in the animal or human immobilizing the affected area since this will help to prevent further injury. However this response is also harmful since the immobility and muscle spasm it produces can cause muscle wasting and weakness. Thoracic and abdominal pain may reduce ventilation and cause hypoxia and hypercapnia. Pain may also cause a marked reduction in food and water consumption. Pain in humans has been shown to prolong the metabolic response to surgery, to increase the requirement for hospital care following operative procedures and to have a range of other detrimental effects.

Provided that surgery has been carried out competently, administration of analgesics to encourage resumption of normal activity by controlling pain, rarely results in problems associated with the removal of pain’s protective function. Claims that analgesic administration results in skin suture removal are unsubstantiated, and contrary to findings in our laboratory. In certain circumstances, for example, after major orthopaedic surgery, additional measures to protect and support the operative site may be required, but this is preferable to allowing an animal to experience unrelieved pain. All that is required in these circumstances is to temporarily reduce the animal’s cage or pen size, or to provide additional external fixation or support for the wound. It must be emphasized that these measures are very rarely necessary, and in our institute, administration of analgesics to laboratory animals after a wide variety of surgical procedures has not resulted in any adverse clinical effects.

“Analgesic drugs have undesirable side-effects such as respiratory depression”

In medical clinical practice, analgesic drugs were frequently withheld because of fears of their undesirable side-effects such as respiratory depression and addiction. This attitude has changed significantly. Side-effects of opioids, such as respiratory depression, are generally less marked in animals than in people and should rarely be a significant consideration when planning a post-operative care regimen. It is, however, important to consider the potential interactions between analgesic therapy and research protocols, and this is discussed in more detail below.

“We do not know the appropriate dose rates and dosage regimens”

Another factor that may limit the use of analgesic drugs is a lack of knowledge of appropriate dose rates and dosage regimens. Safe dose rates are available for a range of drugs in several common laboratory species, but these need to be adjusted to provide effective pain relief to the particular animal being treated – and this requires successful assessment of pain (see below).

“Pain-relieving drugs might adversely affect the results of an experiment”

It is clear that some research scientists are reluctant to administer pain-relieving drugs because their use might adversely affect the results of an experiment. Although there will be occasions when the use of one or other type of analgesic is contra-indicated, it is extremely unlikely that there will be no suitable analgesic that could be administered. More usually, the reluctance to administer analgesics is based upon the misconceived idea that the use of any additional medication in an experimental animal is undesirable. The influence of analgesic administration in a research protocol should be considered in the context of the overall response of the animal to anaesthesia and surgery. As discussed above, the responses to surgical stress may overshadow any possible adverse interactions associated with analgesic administration. In many instances the intra-operative support provided to animals fails to control variables such as body temperature, respiratory function and blood pressure. It seems illogical to assume that these changes are unimportant, but that administration of an analgesic will be of overriding significance. It is an ethical responsibility of a research worker to provide a reasoned, scientific justification if analgesic drugs are to be withheld. 

It is also important to realize that the presence of pain can produce a range of undesirable physiological changes, which may radically alter the rate of recovery from surgical procedures.  In animals, post-surgical pain can reduce food and water consumption, interfere with normal respiration (for example, after thoracotomy) and reduce a whole range of ‘self-maintenance’ behaviours. The immobility caused by pain can lead to muscle spasm, can cause atrophy of areas and can slow healing. Prolonged immobility can also cause pressure sores, urine scalding and faeces soiling and can greatly complicate animal care routines. Immobility in mice also results in a fall in body temperature, and this can have significant and wide-ranging metabolic effects. Positive effects of analgesics have also been reported, for example administration of NSAIDs improved outcomes from embryo transfer in mice.

Finally, there may be legal constraints concerning analgesic use that can restrict their administration. In many countries, the use of the majority of opioids is controlled by legislation (e.g. the Misuse of Drugs Act in the UK). Complying with this legislation often requires careful record keeping of the purchase, storage and dispensing of opioids and may restrict the persons who are able to dispense and administer these substances. In some countries, the degree of record keeping required can act as a strong disincentive to the use of these analgesics in animals. Legislative control, together with genuine safety concerns, may also limit the dispensing of this class of analgesics for use by investigators or technicians. These issues can be addressed by using non-opioid analgesics when these would be appropriate, and by evolving systems of prescribing and supply that make it easier to meet legislative requirements.