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Vet Anaesth Analg. 2014 May;41(3):297-304. doi: 10.1111/vaa.12140. Epub 2014 Feb 27.

Characterisation of tramadol, morphine and tapentadol in an acute pain model in Beagle dogs.

Author information

1
Grünenthal GmbH, Grünenthal Innovation, Global Preclinical R&D, Aachen, Germany.

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 antinociceptive 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:

Beagle dog; acute nociceptive pain; morphine; tapentadol; tramadol

PMID:
24576316
DOI:
10.1111/vaa.12140
[Indexed for MEDLINE]

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