Most alpha 2 agonists exist as racemic mixtures, with most of the pharmacologi-
cal activity associated with one enantiomer; dexmedetomidine, the enantiomer of
medetomidine, is one such example.
4.5 Tramadol
Tramadol has been introduced recently into veterinary medicine, although it has
been used in humans for a number of years. Its pharmacology is of interest in that its
actions resemble those of opioids as well as having effects on catecholamine uptake
(Kayser et al. 1992 ), somewhat similar to alpha 2 agonists. In combination, these
actions have proved to be most effective in humans. In man, tramadol is metabo-
lised to an active metabolite, leading to increased duration of action (Lewis and Hau
1996 ). Tramadol consists of a racemic mixture in which, interestingly, the two
enantiomers are both pharmacologically active, but on different CNS systems. In
view of its relatively high cost, tramadol’s use in animals has been restricted to
small animal species, in which it has a shorter duration of action (Kukanich
and Papich 2004 ). This may be related to limited conversion to the active metabo-
lite (McMillan et al. 2008 ), a property also reported in some groups of humans
(Ogunleye 2001 ). There seems to be a range of activity in different species, which
may be associated with active metabolite formation (Pypendop and Ilkew 2008 )
The relatively wide safety margin and limited side-effects (Scott and Perry 2000 ;
Raffa 2001 ) have led to a number of clinical applications in the control of moderate
to severe clinical pain, particularly for the control of post-operative pain in dogs
and cats.
4.6 Treatment of Neuropathic Pain
An important development in pain detection and control in domestic animals has
been the recognition that animals, like humans, experience neuropathic pain. There
are several factors involved in the pathogenesis of neuropathic pain, involving glial
cells (McMahon et al. 2005 ), neuronal calcium channels (Li et al. 2006 ) and
neuronal sodium channels (Waxman 2007 ), as well as a role for glutamate-
mediated pathways (Ikeda et al. 2007 ). This has led to the use of anticonvulsant
drugs, which interact with glutamate receptors of the NMDA subtype and calcium
channels, in the prevention and treatment of neuropathic pain, both as single agents
and/or as adjuncts to other analgesic therapies such as NSAIDs (Caraceni et al.
1999 ; Blaupied et al. 2005 ). The two drugs most commonly used in veterinary
medicine are amantadine and gabapentin (Lascelles et al.2007b; Lamont et al.
2000 ). Most reports of clinical use have been in dogs. In dogs, unlike humans, in
which species the drug is excreted almost totally unchanged in urine, there is
significant metabolism of gabapentin (Vollmer et al. 1986 ). Another drug that
182 A. Livingston