Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses

Rohrbach, Hélène; Korpivaara, Toni; Schatzmann, U.; Spadavecchia, Claudia

doi:10.1111/j.1467-2995.2009.00466.x

Cited by 76 publications

(68 citation statements)

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“…The most commonly used drugs are the alpha 2 adrenoreceptor agonists (a 2 -agonists); detomidine, xylazine and romifidine, and their sedative and analgesic effects are extensively described in the literature (NANNARONE et al, 2007;ROHRBACH et al, 2009;VALVERDE, 2010). However, due to the insufficient stability of sedation and the short period of action, it is common to combine a 2 -agonists with other drugs, principally opioids, to induce neuroleptanalgesic effects that result in a better degree of sedation/analgesia and more prolonged effects (CLARKE; PATON, 1988;SOLANO et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

A comparison of detomidine in combination with saline, morphine or methadone in horses submitted to experimental oral stimuli

et al. 2015

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A comparison of detomidine in combination with saline, morphine or methadone in horses submitted to experimental oral stimuli Comparação entre a associação da detomidina à solução salina, à morfina ou à metadona em cavalos submetidos aos estímulos experimentais na cavidade oral AbstractThis study aimed to compare the sedative and cardiopulmonary effects of detomidine in combination with saline, morphine or methadone and to determine whether the addition of these opioids increases the degree of sedation in horses submitted to experimental oral stimuli. In a blinded, randomized, experimental study, six adult mares were evaluated using a crossover design with at least 15 days between trials: 10µg/kg detomidine in combination with saline (D/SAL), 0.1mg/kg morphine (D/ MORPH) or 0.1mg/kg methadone (D/METH). The degree of sedation, response to oral stimuli and cardiopulmonary parameters were monitored for 120 minutes. Parametric data were analyzed using the ANOVA and Tukey's tests, and non-parametric data were analyzed with the Kruskal-Wallis and Friedman's tests with the post-Dunn test (P<0.05). The degree of sedation was significantly greater for the D/SAL than for the D/MORPH and D/METH treatments at 30 min. The horses´ responses to the oral stimuli decreased significantly following all treatments at 5 and 30 min from baseline values. The heart rate, respiratory rate, arterial pH and blood gas variables were all similar among the treatment groups. Mean arterial blood pressure was significantly higher in the D/MORPH group when compared with the D/SAL group between 75 and 120 min. It was concluded that all treatments provided sedative effects with mild cardiopulmonary changes. However the addition of morphine or methadone to detomidine did not improve the degree of sedation in horses submitted to experimental oral stimuli. Key words: Alpha 2 adrenoreceptor agonists, dental, equine, opioids ResumoObjetivou-se comparar os efeitos sedativos e cardiorrespiratórios da detomidina associada à solução salina, à morfina ou à metadona e determinar se a associação desses opioides poderia incrementar o grau de sedação em cavalos submetidos aos estímulos na cavidade oral. Em estudo cego, com delineamento aleatório foram avaliadas 06 éguas, com intervalo mínimo de 15 dias entre cada avaliação, sendo submetidos aos protocolos de sedação com detomidina (10mg/kg, IV) associada à solução salina (D/SAL), a 0,1mg/kg (IV) de morfina (D/MORF) ou a 0,1mg/kg (IV) de metadona (D/MET).

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Section: Introductionmentioning

confidence: 99%

A comparison of detomidine in combination with saline, morphine or methadone in horses submitted to experimental oral stimuli

et al. 2015

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“…While the extent of antinociception was comparable among the three drugs, the duration of the antinociceptive activity was drug specific, being longer for romifidine (0.08 mg/kg) than for detomidine (0.02 mg/kg) and xylazine (1 mg/kg). Interestingly, the same was not true for sedation, which was maximal in respect to magnitude and duration for detomidine (Rohrbach et al 2009). …”

Section: Alpha-2 Agonistsmentioning

confidence: 96%

“…From the results obtained in horses it appears that the experimental model applied to quantitatively assess temporal summation is valid and reliable and can be used as an additional tool to assess efficacy of analgesic drugs in these species (Spadavecchia et al 2005, Rohrbach et al 2009). …”

Section: Temporal Summation: Background and Experiences In Horsesmentioning

confidence: 99%

“…Later, the antinociceptive properties of xylazine, romifidine and detomidine, administered intravenously at sedative equipotent doses, were compared in a prospective, blinded, crossover experimental trial using the NWR model (Rohrbach et al 2009). While the extent of antinociception was comparable among the three drugs, the duration of the antinociceptive activity was drug specific, being longer for romifidine (0.08 mg/kg) than for detomidine (0.02 mg/kg) and xylazine (1 mg/kg).…”

Section: Alpha-2 Agonistsmentioning

confidence: 99%

“…Furthermore, all these models merely allow the definition of a single threshold value for each experimental condition, typically measured as the time necessary to obtain a behavioural reaction after stimulation onset. As an alternative, the Nociceptive Withdrawal Reflex (NWR) model has been proposed to investigate the physiology of nociception and to evaluate its modulation by analgesic and anaesthetic drugs in horses (Spadavecchia et al 2002, Spadavecchia et al 2003, Spadavecchia et al 2007, Rohrbach et al 2009). This model not only allows a more reliable definition of the nociceptive threshold through neurophysiological characterization of the elicited response (Spadavecchia et al 2002), but also allows to plot a stimulus-response curve together with the assessment of temporal summation mechanisms (Spadavecchia et al 2004).…”

Section: Introductionmentioning

confidence: 99%

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The model of the Nociceptive Withdrawal Reflex in horses

Spadavecchia¹,

Rohrbach²,

Levionnois³

et al. 2016

PHK

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Summary: In equine pain research, the Nociceptive Withdrawal Reflex (NWR) model has been proposed as an alternative to classical thermal, mechanical and electrical models to investigate the physiology of nociception. This model does not only allow a more reliable definition of the nociceptive threshold through neurophysiological characterization of the elicited response , but also consents plotting a stimulus-response curve as well as the evaluation of temporal summation mechanisms. Aim of this report is to summarize the experience and results obtained using the NWR model in horses over the last 15 years, firstly with the purpose of describing its physiological characteristics and secondly with the aim of evaluating its pharmacological modulation through analgesic and anaesthetic compounds. The NWR can be elicited in horses through electrical transcutaneous stimulation of a peripheral sensory nerve and is recorded through electromyographic electrodes from the muscles involved in the withdrawal reaction. As the non-nociceptive fibres have lower threshold to electrical stimuli than the nociceptive one, it is impossible to differentiate between the two groups on the stimulus side. So, the only guidance to assess the quality of the stimulus and the recruitment of nociceptive afferents should rely on the characteristics of the electromyographic response, most of all on the timing of its various components. A reflex response can be considered to be a true NWR only if it appears within a time epoch compatible with the conduction velocity of the A fibers. Furthermore a clearly recognizable EMG burst in the epoch of interest has to be accompanied by a consistent aversive behavioural reaction, thus allowing the definition of a reliable NWR threshold. Responses to stimulation intensities below and above thresholds can be quantified to draw a stimulus response curve. Furthermore, through repeated stimulation at subthreshold intensities, it is possible to elicit the phenomenon of temporal summation, considered to be the early phase of the wind up phenomenon and of relevant interest to study central integrative mechanisms of pain processing. Alpha-2 agonists, opioids, systemic lidocaine, ketamine and inhalation anaesthetics have been investigated using the NWR model in horses. Drug-specific modulation of NWR threshold, stimulus-response curves and temporal summation are summarized for each tested compound.

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