control of chronic pain following some surgeries (Cassuto et al. 1985 ; Doherty and
Frazier 1998 ).
4.2 Opioids
Drugs of the opioid class have a long history in the control of pain in domestic
animals. Their pharmacological actions are the same or very similar to those
described in humans. The opioid receptors, described as mu, kappa and delta or
OP3, OP2 and OP1, respectively, and various subtypes and orphan receptors have
been identified in all domestic species. The endogenous peptides that bind to the
receptors have been described (Nolan 2000 ).
There are, however, species differences in the distribution and location of opioid
receptors and consequently differences have been described in the responses to
various opioid drugs. Fortunately, the significant and major role of endogenous
opioid peptides as processors of nociceptive information within the CNS is present
and similar in all domestic species, including non-mammalian species. Hence, the
use of opioid drugs as analgesic agents is practised across the species spectrum.
Recommended dose rates in a range of species of domestic animals have been
published for a wide range of opioid analgesics, including buprenorphine, butor-
phanol, fentanyl, methadone, morphine, nalbuphine, oxymorphone, pentazocine
and pethidine and also for naloxone the opioid antagonist. The species for which
clinical and dosage data are available include laboratory animals (Flecknell 1996 ),
dogs and cats (Papich 2000 ) and farm animals (Thurman et al. 1996 ) as well as birds
(Machin 2005 ) and reptiles (Mosley 2005 ). Factors determining dosage of opioids in
domestic animals include hepato-metabolism, which is particularly rapid in labora-
tory rodents (Morris 1995 ), the sensitivity of dogs to the emetic actions of morphine,
and an oft reported but rarely seen hypotensive effect associated with histamine
release. In cats, dysphoria or other CNS effects are occasionally seen with opioid
use, but this is usually associated only with very high dose rates (Papich 2000 ).
However, in horses, excitement or stereotypical behaviour may occur, particularly
with the mu agonists at lower dose rates (Mama et al. 1992 ). Similar effects have
also been reported in ruminants (Livingston et al. 1991 ). Pigs seem to require
relatively high doses to provide effective analgesia but other behavioural effects
have not been reported. The most significant side-effect associated with opioid use
in humans is respiratory depression and this is also the case in domestic animals in
cases of overdose. Another major human concern with opioid use is that of its
dependence/abuse. Whilst both tolerance and dependence can also be demonstrated
in domestic animals, the administration of opioids is usually restricted to short-term
dosing for either acute pain or perioperative use and therefore dependence is not
considered to be an issue in these clinical situations. Drugs such as morphine, which
have pharmacologically active glucuronide metabolites in humans, also show this
characteristic in animals but, because of variations in the rates of hepatometabolism,
the significance of these metabolites in animals is uncertain.
176 A. Livingston