between the epithelial cells, while thiscondition does not exist in stallions or
in bulls.
Xylazine, an alpha2-adrenergic agonist, used widely in several species as a
sedative, is also a reliable emetic, particularly in cats, in which it stimulates the
chemoreceptor trigger zone (CTZ) in the medulla oblongata, while it does not
induce emesis in species such as ruminants and horses lacking the vomiting reflex.
In the preceding examples, the interspecies differences were easily explained by
anatomical, biochemical, histological, or physiological differences. However, this
is seldom the case when species are compared for functions involving the central
nervous system, for example with some behavioural responses and the response to
pain. The International Association for the Study of Pain (ISAP) defines pain in
man as “an unpleasant sensory and emotional experience associated with actual or
potential tissue damage, or described in terms of such damage”. This definition is
not directly transposable to animals due to its cognitive dimension. Therefore,
pharmacologists prefer the use of the word “nociception” to describe what they
observe, as for any other somatosensation. There is evidence of nociception across
all domestic species including fish. However, what is particularly difficult to
appreciate let alone quantify, when evaluating the benefit of analgesic therapy in
animals, is the level of suffering across species, because suffering implies a mental
dimension and there are no means of quantifying levels of suffering.
Observations of animal behaviour as a basis for assessing pain can be very
misleading, especially when using some resilient behaviour. Resilience is a passive
adaptative strategy to cope with adversity including pain. For example, the ass is a
resilient species that expresses its pain only at a high threshold, while the opposite
applies to horses (Ashley et al. 2005 ). This creates problems for the assessment of
presence and level of pain and the efficacy of analgesics in asses; conditions such as
colic can proceed to advanced irreversible stages before they are detected. Resil-
ience may also be observed in dogs in some circumstances; Hansen ( 2003 ) reported
that, until recently, dogs in his intensive care unit did not receive analgesics after
major surgery, in part because they did not meet the expectations of their caregivers
for pain behaviour. Some strains of beagles have been deliberately selected and/or
trained to express resilient and passive behaviour as a desirable trait in investiga-
tions concerning toxicology assessment but these unresponsive dogs are inappro-
priate for testing analgesic drugs (Toutain, unpublished observations). There is
experimental evidence in both mice and man that responsiveness to pain may be
modulated by social status and the social environment and also that empathy exists
in animals; it has been reported that expression of pain in a test subject may be
influenced by the presence or absence of a familiar conspecific animal, rendering
the assessment of analgesic efficacy complicated (Gioiosa et al. 2009 ; Langford
et al. 2006 ). For fish, the situation is even less clear and there is no consolidated
indicator of pain, so that efficacy of analgesia associated with general anaesthesia is
often judged by the ability to handle fish without difficulty. For a review on the
difficulties of assessing pain, see Anil et al. ( 2002 ). Animal pain, including anthro-
pomorphic considerations, is reviewed in the chapter, “Pain and Analgesia in
Domestic Animal Species” of this text.
Species Differences in Pharmacokinetics and Pharmacodynamics 29