Abstract
Objective
To evaluate the analgesic potential of the centrally acting analgesics tramadol, morphine
and the novel analgesic tapentadol in a pre-clinical research model of acute nociceptive
pain, the tail-flick model in dogs.
Study design
Prospective part-randomized pre-clinical research trial.
Animals
Fifteen male Beagle dogs (HsdCpb:DOBE), aged 12–15 months.
Methods
On different occasions separated by at least 1 week, dogs received intravenous (IV)
administrations of tramadol (6.81, 10.0 mg kg−1), tapentadol (2.15, 4.64, 6.81 mg kg−1) or morphine (0.464, 0.681, 1.0 mg kg−1) with subsequent measurement of tail withdrawal latencies from a thermal stimulus
(for each treatment n = 5). Blood samples were collected immediately after the pharmacodynamic measurements
of tramadol to determine pharmacokinetics and the active metabolite O-demethyltramadol (M1).
Results
Tapentadol and morphine induced dose-dependent antinociception with ED50-values of
4.3 mg kg−1 and 0.71 mg kg−1, respectively. In contrast, tramadol did not induce antinociception at any dose tested.
Measurements of the serum levels of tramadol and the M1 metabolite revealed only marginal
amounts of the M1 metabolite, which explains the absence of the antinociptive effect
of tramadol in this experimental pain model in dogs.
Conclusions and clinical relevance
Different breeds of dogs might not or only poorly respond to treatment with tramadol
due to low metabolism of the drug. Tapentadol and morphine which act directly on μ-opioid
receptors without the need for metabolic activation are demonstrated to induce potent
antinociception in the experimental model used and should also provide a reliable
pain management in the clinical situation. The non-opioid mechanisms of tramadol do
not provide antinociception in this experimental setting. This contrasts to many clinical
situations described in the literature, where tramadol appears to provide useful analgesia
in dogs for post-operative pain relief and in more chronically pain states.
Keywords
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Article info
Publication history
Accepted:
July 15,
2013
Received:
February 4,
2013
Identification
Copyright
© 2014 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Inc. All rights reserved.
