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Assessment of a von Frey device for evaluation of the antinociceptive effects of morphine and its application in pharmacodynamic modeling of morphine in dogs

Butch KuKanich DVM, PhD1,2, B. Duncan X. Lascelles BVSc, PhD3, and Mark G. Papich DVM, MS4
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  • 1 Department of Molecular Biomedical Sciences, Pharmacology and Comparative Pain Research Laboratories, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 2 Present address is the Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506-5802.
  • | 3 Department of Clinical Sciences, Pharmacology and Comparative Pain Research Laboratories, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 4 Department of Molecular Biomedical Sciences, Pharmacology and Comparative Pain Research Laboratories, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

Abstract

Objective—To assess the use of a von Frey device as a mechanical nociceptive stimulus for evaluation of the antinociceptive effects of morphine in dogs and its potential application in the pharmacodynamic modeling of morphine in that species.

Animals—6 healthy Beagles.

Procedure—von Frey thresholds were measured in all dogs before and at intervals after they received no treatment (control dogs) and IV administration of morphine sulfate (1 mg/kg; treated dogs) in a crossover study. The von Frey device consisted of a rigid tip (0.5 mm in diameter) and an electronic load cell; the operator was unaware of recorded measurements.

Results—Application of the von Frey device was simple and well tolerated by all dogs and caused no apparent tissue damage. No significant changes in thresholds were detected in the control dogs at 8 hourly measurements, indicating a lack of acquired tolerance, learned aversion, or local hyperalgesia. When assessed as a group, treated dogs had significantly high thresholds for 4 hours following morphine administration, compared with baseline values; individually, thresholds decreased to baseline values within (mean ± SE) 2.8 ± 0.6 hours. The maximal effect (change from baseline values) was 213 ± 43%, and the plasma morphine concentration to achieve 50% maximal effect was 13.92 ± 2.39 ng/mL.

Conclusions and Clinical Relevance—Data suggest that, in dogs, evaluation of the antinociceptive effect and pharmacodynamic modeling of a dose of morphine sulfate (1 mg/kg, IV) can be successfully achieved by use of a von Frey device. (Am J Vet Res 2005;66:1616–1622)

Abstract

Objective—To assess the use of a von Frey device as a mechanical nociceptive stimulus for evaluation of the antinociceptive effects of morphine in dogs and its potential application in the pharmacodynamic modeling of morphine in that species.

Animals—6 healthy Beagles.

Procedure—von Frey thresholds were measured in all dogs before and at intervals after they received no treatment (control dogs) and IV administration of morphine sulfate (1 mg/kg; treated dogs) in a crossover study. The von Frey device consisted of a rigid tip (0.5 mm in diameter) and an electronic load cell; the operator was unaware of recorded measurements.

Results—Application of the von Frey device was simple and well tolerated by all dogs and caused no apparent tissue damage. No significant changes in thresholds were detected in the control dogs at 8 hourly measurements, indicating a lack of acquired tolerance, learned aversion, or local hyperalgesia. When assessed as a group, treated dogs had significantly high thresholds for 4 hours following morphine administration, compared with baseline values; individually, thresholds decreased to baseline values within (mean ± SE) 2.8 ± 0.6 hours. The maximal effect (change from baseline values) was 213 ± 43%, and the plasma morphine concentration to achieve 50% maximal effect was 13.92 ± 2.39 ng/mL.

Conclusions and Clinical Relevance—Data suggest that, in dogs, evaluation of the antinociceptive effect and pharmacodynamic modeling of a dose of morphine sulfate (1 mg/kg, IV) can be successfully achieved by use of a von Frey device. (Am J Vet Res 2005;66:1616–1622)