Narcotic analgesics, their detection and pain measurement in the horse: a review.

Narcotic analgesics produce pharmacological effects by interacting with specific opiate receptors. At least five major types of opiate receptors have been recognised. These include mu (morphine) and kappa (ethylketazocine) receptor types. Narcotic analgesics which interact with mu receptors produce locomotor and autonomic stimulation at doses that produce little or no analgesia. Therefore, use of these drugs as analgesics in equine medicine has not been very satisfactory. Theoretical considerations suggested that the role of kappa agonists in equine analgesia be investigated. Using a pure kappa agonist, U-50, 488H, good analgesia was produced in the horse with little or no locomotor stimulation or autonomic effects. These data suggest that kappa agonists may be superior analgesics for clinical use in the horse. On the other hand, the locomotor stimulant effects of mu agonist analgesics enable their use as illegal medications. Specifically, these agents produce a good running response, signs of central nervous stimulation and analgesia, all potentially useful effects in a racehorse. Regulatory control of most narcotic analgesics can be obtained by high performance thin layer chromatographic screening. However, effective screening for the fentanyls and small doses of etorphine can only be achieved by use of immunoassay.

Dose-related effects of ethylketazocine on nociception, behaviour and autonomic responses in the horse.

Sensitive methods for measuring the analgesic, physiological and behavioural effects of opioids in the horse have recently been developed. Fentanyl, a prototypic mu-opiate receptor agonist, has been previously shown to produce a syndrome characterized by marked analgesia and locomotor stimulation as well as tachycardia, tachypnoea and behavioural arousal. To determine whether other opiate receptors mediate some of the actions of the narcotic analgesics in the horse, an agent with activity at kappa- and to lesser extent mu-receptors was studied using a vigorous experimental protocol. Like fentanyl, ethylketazocine (EKC) (0.0025-0.012 mg kg-1 i.v.) produced marked dose-related analgesia to noxious thermal stimuli. Modest dose-related increases in locomotor activity, pupil diameter and rectal temperature were also observed. However, in contrast to fentanyl, EKC failed to produce any change in cardiac or respiratory rates and produced behavioural sedation rather than arousal. These data suggest that mu- and possibly kappa-receptors can mediate the actions of narcotics in the horse.

A method for studying cutaneous pain perception and analgesia in horses.

Pain perception and its alteration by analgesic drugs is difficult to measure in the horse. The latency to onset of flexion of a limb in response to a noxious thermal stimulus has been used as a nociceptive end point for analgesic studies in many species. While this method has been employed in the horse, it may be confounded by the spontaneous locomotor activity observed after administration of narcotic analgesics. Consequently, an alternative method of assaying narcotic analgesia that did not involve the equine locomotor apparatus was developed. This report describes the use of the heat-evoked skin-twitch reflex as a reproducible measure of pain threshold and its alteration by the narcotic analgesic fentanyl. This method is compared with the heat-evoked hoof-withdrawal reflex, and the apparatus necessary to elicit both reflexes in the horse is described. Fentanyl, administered at intravenous doses of 0.010, 0.005, and 0.0025 mg/kg, produced a dose-related prolongation of the skin-twitch reflex but failed to alter the latency to hoof withdrawal following noxious thermal stimulation. The skin-twitch reflex is therefore a more sensitive assay of narcotic analgesia in the horse than is the hoof-withdrawal reflex.

Dose-related effects of fentanyl on autonomic and behavioral responses in performance horses.

The dose-related effects of intravenously administered fentanyl (0.010, 0.005, 0.0025 mg/kg) and saline were studied in mature performance horses using a rigorous experimental protocol. Fentanyl produced a dose-related prolongation of the skin twitch reflex latency but did not increase the hoof withdrawal reflex latency. Dose related increases in stepping frequency, cardiac and respiratory rats were observed following fentanyl, while changes in rectal temperature and pupil area were not. These data indicate that fentanyl, a prototypic mu-agonist, produces a syndrome characterized by analgesia, locomotor and sympathetic stimulation in the horse.

Differential effects of phenylbutazone and local anesthetics on nociception in the equine.

The effects of procaine, mepivacaine and phenylbutazone on pain perception in the equine were studied using two behavioral assays of nociception; the thermal evoked hoof withdrawal reflex and skin twitch reflex. Pain perception threshold was measured as the latency from onset of thermal stimuli to reflex withdrawal of the forelimb or contraction of the cutaneous musculature. Procaine 2% and mepivacaine 2% prolonged the hoof withdrawal reflex latency when administered locally by producing a block of the palmar and metacarpal nerves. Significant analgesia lasted 90 min and 210 min for procaine and mepivacaine, respectively. Phenylbutazone (7.3 mg/kg) failed to alter pain thresholds measured over a 36 h post-treatment period. However, pain thresholds rose over time with successive trials. These data suggest that in the equine (1) phenylbutazone does not alter normal cutaneous pain perception, and (2) successive presentation of painful stimuli increases nociceptive thresholds.