Effect of detomidine on visceral and somatic nociception and duodenal motility in conscious adult horses

https://doi.org/10.1111/j.1467-2995.2008.00441.xGet rights and content

Abstract

Objective

To evaluate the effects of detomidine on visceral and somatic nociception, heart and respiratory rates, sedation, and duodenal motility and to correlate these effects with serum detomidine concentrations.

Study design

Nonrandomized, experimental trial.

Animals

Five adult horses, each with a permanent gastric cannula weighing 534 ± 46 kg.

Methods

Visceral nociception was evaluated by colorectal (CRD) and duodenal distension (DD). The duodenal balloon was used to assess motility. Somatic nociception was assessed via thermal threshold (TT). Nose–to–ground (NTG) height was used as a measure of sedation. Serum was collected for pharmacokinetic analysis. Detomidine (10 or 20 μg kg−1) was administered intravenously. Data were analyzed by means of a three–factor anova with fixed factors of treatment and time and random factor of horse. When a significant time × treatment interaction was detected, differences were compared with a simple t–test or Bonferroni t–test. Significance was set at p < 0.05.

Results

Detomidine produced a significant, dose–dependent decrease in NTG height, heart rate, and skin temperature and a significant, nondose–dependent decrease in respiratory rate. Colorectal distension threshold was significantly increased with 10 μg kg−1 for 15 minutes and for at least 165 minutes with 20 μg kg−1. Duodenal distension threshold was significantly increased at 15 minutes for the 20 μg kg−1 dose. A significant change in TT was not observed at either dose. A marked, immediate decrease in amplitude of duodenal contractions followed detomidine administration at both doses for 50 minutes.

Conclusions and clinical relevance

Detomidine caused a longer period of visceral anti–nociception as determined by CRD but a shorter period of anti–nociception as determined by DD than has been previously reported. The lack of somatic anti–nociception as determined by TT testing may be related to the marked decrease in skin temperature, likely caused by peripheral vasoconstriction and the low temperature cut–off of the testing device.

Introduction

Detomidine is an alpha–2–adrenoreceptor agonist commonly used in horses to provide both sedation and analgesia. Its sedative and analgesic effects are produced via binding to alpha–2 receptors in the locus ceruleus complex in the brainstem and spinal cord (Owens et al. 1996; Daunt & Steffey 2002). It produces profound muscle relaxation by causing inhibition of excitatory neurotransmitter release from spinal interneurons (Nollet et al. 2003). These actions result in the characteristic dose–dependent head drop, ataxia, and decreases in heart rate, respiratory rate and gastrointestinal motility (Daunt et al. 1993; Daunt 1995; Freeman & England 2000; Wilson et al. 2002).

Detomidine has documented analgesic properties in horses. For example, detomidine was shown to be an effective analgesic in a laminitis model of chronic pain and a model of cutaneous thermal stimulation, using a heat lamp, although not in a chronic tendon injury model (Kamerling et al. 1988; Chambers et al. 1993; Owens et al. 1996). Detomidine also produced visceral analgesia in a cecal distension model (Lowe & Hilfiger 1986) and is used clinically as both a sedative for diagnostic procedures and therapeutically to alleviate abdominal pain in horses (Clarke & Taylor 1986). The duration of action in these reports is variable, and few studies have documented the effects of doses at the lower end of the recommended range (0.01–0.02 mg kg−1).

The purposes of this study were threefold to: (1) evaluate the somatic and visceral analgesic effects of detomidine using a cutaneous thermal threshold (TT) model of somatic nociception and colorectal (CRD) and duodenal distension (DD) models of visceral nociception; (2) correlate plasma detomidine concentrations with its analgesic effects; and (3) objectively assess the effects of detomidine on duodenal motility.

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Animals

Five adult Thoroughbred horses (three mares, two geldings, weighing 534 ± 46, range 491–615 kg) each with a permanently implanted gastric cannula (Campbell–Thompson & Merritt 1987) were used in the study. Between trials, horses were housed on pasture where they had free access to water, mineral block, paddock grass, coastal hay and received 10% sweet feed twice daily to maintain body condition. The horses were moved to a stall 12–18 hours prior to each trial where they had free access to water

Results

All horses remained standing and restrained in the stocks, during both treatments, with no obvious untoward effects. The duodenal balloon was not placed in one horse during the 10 μg kg−1 treatment as a result of a technical malfunction. Baseline DD threshold pressures (Fig. 1) did not differ significantly between doses (26 ± 3 and 29 ± 7 mmHg for the 10 and 20 μg kg−1 doses, respectively). Following the 20 μg kg−1 dose, there was a significant increase in threshold pressure at 15 minutes to

Discussion

Detomidine produced a dose–dependent anti–nociceptive effect in response to visceral distension but a somatic anti–nociceptive effect in response to a thermal stimulus was not demonstrated. The doses used in this study (10 and 20 μg kg−1) are representative of those used clinically for sedation and analgesia of the horse for both diagnostic and therapeutic purposes. Because the anti–nociceptive effects of detomidine have been previously documented at higher doses, the aim was to compare the two

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