Studies on renal safety and preventive analgesic efficacy of tramadol and parecoxib in dogs : thesis in fulfilment of the degree of Doctor of Philosophy in Veterinary Clinical Science, Institute of Veterinary Animal and Biomedical Sciences, College of Sciences, Massey University, Palmerston North, New Zealand
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Date
2008
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Massey University
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Abstract
Ovariohysterectomy and castration are common surgical procedures in small animal practice
that can result in clinically significant postoperative pain. One way of controlling
postoperative pain is administration of a single analgesic or a combination of different classes
of analgesics prior to the onset of noxious stimuli. A constraint to the perioperative use of
traditional opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is their undesirable
side effects. In this series of experiments, the preventive (pre-emptive) analgesic efficacy of
two popular human analgesics, tramadol (an ?atypical? opioid) and parecoxib (a NSAID with
selective COX-2 inhibition) was evaluated in dogs.
Initially, the efficacy and renal safety of parecoxib, tramadol and a combination of parecoxib,
tramadol and pindolol (a -adrenoceptor blocker and 5-HT1A/1B antagonist) were screened
in anaesthetised healthy dogs. These analgesics increased the dogs? nociceptive threshold to
mechanical stimuli, without causing significant alterations in the dogs? glomerular filtration
rate (GFR) estimated by plasma iohexol clearance. Subsequently, the efficacy of tramadol
was compared with morphine, in dogs undergoing ovariohysterectomy or castration. The
Glasgow composite measure pain scale-short form score (CMPS-SF) and changes in intraoperative
electroencephalogram (EEG) responses were used to assess the efficacy of
analgesics. Of the three treatment groups (preoperative morphine, 0.5 mg kg-1; preoperative
tramadol, 3 mg kg-1; a ?combination? of preoperative low-dose morphine, 0.1 mg kg-1, and
postoperative tramadol 3 mg kg-1), dogs given the ?combination? had significantly lower pain
scores after ovariohysterectomy. In castrated dogs, preoperative tramadol (3 mg kg-1) and
morphine (0.5 mg kg-1) were tested and no significant difference in the CMPS-SF score were
observed between them. Changes in EEG variables were not specific between the treatment
groups in ovariohysterectomised dogs.
Finally, the efficacy of test drugs was evaluated against acute noxious electrical stimulation
in anaesthetised dogs, using EEG. Median frequency of the EEG, a reliable indicator of
nociception, increased significantly in tramadol and parecoxib groups, compared to
morphine, after electrical stimulation. These studies demonstrated that tramadol and
parecoxib can produce analgesia in dogs with insignificant side effects. The efficacy of
tramadol appears to vary with the type of noxious stimulus. A complete prevention of
noxious input by administration of analgesics pre- and post-operatively could have important
clinical applications.
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Keywords
Analgesics, Anaesthesia, Pain relief, Dog surgery, Pain in animals