Opioids in horses refer to a class of drugs that interact with opioid receptors in the central nervous system to produce analgesic effects. These substances are used in veterinary medicine for pain management, sedation, and anesthesia in equine patients. Opioids such as morphine, butorphanol, and buprenorphine are commonly administered to horses to alleviate pain associated with surgical procedures, injury, or chronic conditions. The pharmacokinetics and pharmacodynamics of opioids in horses can vary, influencing their efficacy and safety profiles. This topic includes a collection of peer-reviewed research studies and scholarly articles that explore the use, effects, and considerations of opioid administration in equine veterinary practice.
Pallarols NB, Lamuraglia R, Guglielminetti A, Ortiz de Elguea MF, Carossino M, Funcia JP.Xylazine and remifentanil in constant rate infusion (CRI) could be used for sedation in horses without adverse effects. The objective was to evaluate behavioral and cardiopulmonary effects of an intravenous (IV) infusion of xylazine and remifentanil for sedation in horses. Xylazine (0.8 mg/kg IV) followed after 3 minutes by a CRI of xylazine and remifentanil (0.65 mg/kg/h and 6 μg/kg/h, respectively) was administered in 10 healthy horses for 60 minutes. Sedation, ataxia, and cardiopulmonary, hematological, and blood gases variables were evaluated. Heart rate decreased significantly durin...
Martins FC, Keating SC, Clark-Price SC, Schaeffer DJ, Lascola KM, DiMaio Knych H.To determine the physiologic and behavioral effects and pharmacokinetic profile of hydromorphone administered intravenously (IV) to horses. Methods: Prospective, randomized, crossover study. Methods: A group of six adult healthy horses weighing 585.2 ± 58.7 kg. Methods: Each horse was administered IV hydromorphone (0.025 mg kg; treatment H0.025), hydromorphone (0.05 mg kg; treatment H0.05) or 0.9% saline in random order with a 7 day washout period. For each treatment, physiologic, hematologic, abdominal borborygmi scores and behavioral data were recorded over 5 hours and fecal output was tota...
Mirra A, Birras J, Diez Bernal S, Spadavecchia C.Epidural administration of morphine has been shown to be an effective analgesic strategy in horses; however, the possible occurrence of side effects limits its usage. In order to decrease their frequency, it is important to target the minimal effective plasma concentration and avoid overdosing. As to date species-specific pharmacokinetics data are not available for epidural morphine, the dosing regimen is usually established on the basis of clinical reports and personal experience. In certain physiological conditions, like gestation, the outcome of an empirical dosing scheme can be unpredictab...
Reed RA, Knych HK, Barletta M, Sakai DM, Ruch MM, Smyth CA, Ryan CA.To compare the pharmacokinetics and pharmacodynamics of hydromorphone in horses after intravenous (IV) and intramuscular (IM) administration. Methods: Randomized, masked, crossover design. Methods: A total of six adult horses weighing [mean ± standard deviation (SD))] 447 ± 61 kg. Methods: Horses were administered three treatments with a 7 day washout. Treatments were hydromorphone 0.04 mg kg IV with saline administered IM (H-IV), hydromorphone 0.04 mg kg IM with saline IV (H-IM), or saline IV and IM (P). Blood was collected for hydromorphone plasma concentration at multiple time points for ...
Gozalo-Marcilla M, Moreira da Silva R, Pacca Loureiro Luna S, Rodrigues de Oliveira A, Werneck Fonseca M, Peporine Lopes N, Taylor PM, Pelligand L.The alpha(α) -agonist detomidine is used for equine sedation with opioids such as methadone. We retrieved the data from two randomized, crossover studies where detomidine and methadone were given intravenously alone or combined as boli (STUDY 1) (Gozalo-Marcilla et al., 2017, Veterinary Anaesthesia and Analgesia, 2017, 44, 1116) or as 2-hr constant rate infusions (STUDY 2) (Gozalo-Marcilla et al., 2019, Equine Veterinary Journal, 51, 530). Plasma drug concentrations were measured with a validated tandem Mass Spectrometry assay. We used nonlinear mixed effect modelling and took pharmacokinetic...
Skiöldebrand E, Ley C, Björklund U, Lindahl A, Hansson E.Osteoarthritis is a pain-associated progressive disease and pain mediators, such as opioid receptors, expressed in articular cartilage could represent novel therapeutic targets. Acute and chronic stages of OA indicate different metabolic abilities of the chondrocytes depending on inflammatory state. This study aimed to investigate the response of healthy and osteoarthritic chondrocytes and their expression and release of pain mediators in response to acute inflammation. Interleukin-1 beta (IL-1β) and lipopolysaccharide (LPS) were used to induce an acute inflammatory response in cultured equin...
Briefer Freymond S, Bardou D, Beuret S, Bachmann I, Zuberbühler K, Briefer EF.Although stereotypic behaviors are a common problem in captive animals, why certain individuals are more prone to develop them remains elusive. In horses, individuals show considerable differences in how they perceive and react to external events, suggesting that this may partially account for the emergence of stereotypies in this species. In this study, we focused on crib-biting, the most common stereotypy displayed by horses. We compared how established crib-biters ("CB" = 19) and normal controls ("C" = 18) differed in response to a standard "personality" assessment test battery, i.e., react...
Frigerio MA, Gómez Cisneros D, Santiago Llorente I, Manso-DÃaz G, López-Sanromán J.Chemical restraint is often used to perform diagnostic and minor surgical procedures; α2 -adrenoceptor agonists are the most commonly used drugs; however, the combination with an opiate can induce a profound sedation. There is a lack of kinematic studies examining the effects of the combination of these drugs on locomotor patterns. Objective: The objective of the study was to evaluate the duration of the effects of sedation with detomidine and detomidine combined with a low dose of butorphanol on the movement patterns of horses. Methods: The study was a controlled, randomised, blinded and cro...
Tessier C, Pitaud JP, Thorin C, Touzot-Jourde G.There are no data investigating the effect of systemic morphine on the size of the stomach or the food consumption in horses. Objective: To evaluate gastrointestinal side effects of morphine administered systemically in healthy horses by the means of clinical and ultrasonographic evaluations. Methods: In vivo experiment. Methods: On day 1 of the experiment, six healthy French Trotter mares were evaluated clinically and an abdominal ultrasonography was performed three times 4Â h apart to record the size of the stomach, the number of contractions per minute of the duodenum, jejunum, caecum, left...
Hamamoto-Hardman BD, Steffey EP, Weiner D, McKemie DS, Kass P, Knych HK.The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5Â mg/kg, or saline control. Blood samples were collected up to 72Â hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total prote...
Schwarzbach SV, Melo CF, Xavier PLP, Roballo KC, Cordeiro YG, Ambrósio CE, Fukumasu H, Carregaro AB.Osteoarthritis (OA) is one of the main locomotor disorders in horses. Although nonsteroidal anti-inflammatory drugs are the first-line treatment for OA, opioids could also be used. In previous studies, opioids showed promising anti-inflammatory and analgesic effects. In this study, we aimed to investigate the effects of two opioids (morphine and methadone) against inflammation in lipopolysaccharide (LPS)-stimulated synoviocytes by analyzing microsomal prostaglandin E synthase-1 (mPGES-1) and prostaglandin-endoperoxide synthase 2 (PTGS2) expression. Synoviocytes were obtained from the joints at...
Reed R, Barletta M, Mitchell K, Hanafi A, Bullington A, Knych H, Quandt J, Ryan C, Giguère S.Describe the pharmacokinetics and pharmacodynamics of intravenous hydromorphone in healthy horses. Methods: Masked, randomized, cross-over, Latin square design. Methods: A group of eight healthy adult horses METHODS: Horses were administered each of four treatments with an 8 day washout. Treatments groups included intravenous hydromorphone 0.02 mg kg (LD), 0.04 mg kg (MD), 0.08 mg kg (HD) and saline (P). Blood samples for hydromorphone analysis were obtained for 24 hours after treatment. Plasma hydromorphone was quantified and pharmacokinetic parameters were determined using non-compartmental ...
Levionnois OL, Graubner C, Spadavecchia C.To investigate the pharmacological profile and side effects of buprenorphine administered as a sustained-release formulation in horses. Methods: Pilot trial. Methods: A total of four experimental horses, aged 18-27 years and weighing 508-578 kg. Methods: Buprenorphine (0.1 mg kg) was mixed as a freshly prepared sterile solution with a sustained-release drug carrier. It was administered by the subcutaneous (n = 2) or intramuscular (n = 2) route. During the experiment, the horses were closely monitored, equipped with a step counter and blood samples were collected for quantification of bup...
Hemmings A, Parker MO, Hale C, McBride SD.Spontaneous stereotypic behaviours are repetitive, compulsive, topographically invariant response patterns commonly observed in captive or domestic animals, which have been linked to dysfunction of basal ganglia input/output pathways. There is evidence that endogenous opioids play a key regulatory role in basal ganglia direct and indirect pathways, but their precise role, both causally and functionally, in spontaneous stereotypic behaviour is unclear. Here we examined the profile of mu- and delta-opioid receptors (density [Bmax] and affinity [Kd]) of basal ganglia structures in stereotypy (nâ€...
Rowland AL, Glass KG, Grady ST, Cummings KJ, Hinrichs K, Watts AE.To determine the influence of epidural detomidine and morphine on serum corticosteroid concentrations and pain-related behavioral responses in mares during and after ovariectomy via colpotomy. Methods: Blinded prospective study. Methods: Nine university-owned mares. Methods: Five of 9 horses received caudal epidural detomidine hydrochloride (0.01 mg/kg) and morphine sulfate (0.1 mg/kg) prior to surgery. All horses received local anesthetic around the ovarian pedicle, 0.02 mg/kg butorphanol IV at the start of the procedure and after first ovary removal, were sedated as required throughout the p...
Sandbaumhüter FA, Vimercati S, Thormann W, Mevissen M.The anesthetic ketamine is often combined with analgesics and benzodiazepines in equine medicine. Therefore, drug-drug interactions are possible. Enzyme kinetics for ketamine N-demethylation were determined using equine CYP3A94, CYP3A95 and CYP3A97, and the effect of medetomidine, diazepam and methadone on the ketamine metabolism was studied in vitro. Ketamine was incubated with the CYPs or equine liver microsomes (ELM) alone or in presence of medetomidine, diazepam and/or methadone for different times. Norketamine levels were determined using enantioselective capillary electrophoresis (CE) wi...
This work proposes an application of a minimal complexity physiologically based pharmacokinetic model to predict tramadol concentration vs time profiles in horses. Tramadol is an opioid analgesic also used for veterinary treatments. Researchers and medical doctors can profit from the application of mathematical models as supporting tools to optimize the pharmacological treatment of animal species. The proposed model is based on physiology but adopts the minimal compartmental architecture necessary to describe the experimental data. The model features a system of ordinary differential equations...
Dönselmann Im Sande P, Hopster K, Kästner S.Various opioids are available for use in equine medicine. Studies directly comparing their analgesic effects and side effects are rare. Therefore, the aim of this study was to compare the antinociceptive effect and the duration of analgesia of two different doses of morphine, butorphanol and levomethadone in horses. Methods: Eight adult, healthy horses were used for this randomized, placebo-controlled, blinded cross-over trail. Each horse received placebo (P = 0.9% saline) and morphine (M = 0.1 mg/kg; M = 0.2 mg/kg), butorphanol (B = 0.1 mg/kg; B = 0.2 mg/kg) and levomethadone (L...
Wetmore LA, Pascoe PJ, Shilo-Benjamini Y, Lindsey JC.OBJECTIVE To determine the locomotor response to the administration of fentanyl in horses with and without the G57C polymorphism of the μ-opioid receptor. ANIMALS 20 horses of various breeds and ages (10 horses heterozygous for the G57C polymorphism and 10 age-, breed-, and sex-matched horses that did not have the G57C polymorphism). PROCEDURES The number of steps each horse took was counted over consecutive 2-minute periods for 20 minutes to determine a baseline value. The horse then received a bolus of fentanyl (20 μg/kg, IV), and the number of steps was again counted during consecutive 2-...
Madry MM, Spycher BS, Kupper J, Fuerst A, Baumgartner MR, Kraemer T, Naegeli H.Compared to blood or urine, drugs can be detected for much longer periods in the long hair of horses. The aim of this study was to establish and validate a highly sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the detection and quantification of frequently prescribed opioids, sedatives and non-steroidal anti-inflammatory agents in the mane and tail hair of horses. Based on an average growth rate of about 2 cm per month, times of administration reported by horse owners or veterinary physicians were related to drug localizations in hair. Hair samples were collecte...
Knych HK, Steffey EP, White AM, McKemie DS.Tramadol is an analgesic agent used in man and a number of veterinary species. The pharmacokinetics and behavioural effects of tramadol and its active metabolite have been described in mature horses, but not in young foals. Objective: To characterise the pharmacokinetics, metabolism and some induced behavioural and physiological responses following i.v. tramadol administration in the same group of foals on 4 different occasions, from a few days after birth to age 43 days. Methods: Experimental. Methods: Tramadol was administered i.v. (3 mg/kg bwt) to a group of 8 foals on 4 separate occasion...
General anaesthesia in horses is associated with elevated mortality rate in subjects suffering of heaves. Target-controlled infusion (TCI) of sedative-hypnotic medications and opioids represents a total intravenous anaesthesia (TIVA) method validated in veterinary medicine. Since there are no data concerning the impact of these classes of drugs in inducing bronchial hyperresponsiveness (BHR) in horses, the aim of this study was to investigate the effect propofol and remifentanil on the contractile response of equine airway smooth muscle. The influence of propofol and remifentanil on the contra...
Hunter BG, Parker JE, Wehrman R, Stang B, Cebra CK.To determine synovial concentrations of morphine after intravenous regional limb perfusion (IVRLP) with morphine or morphine in combination with gentamicin in clinically healthy, standing sedated horses. Methods: Experimental. Methods: Adult horses (n = 6). Methods: IVRLP was performed using 0.1 mg/kg morphine (M) in standing sedated horses. After a 3-week washout period, IVRLP was performed on the same forelimb with a combination of 0.1 mg/kg morphine and 1 g gentamicin (M/G). Synovial fluid from the middle carpal joint of the perfused limb and jugular blood samples were collected i...
Taylor PM, Hoare HR, de Vries A, Love EJ, Coumbe KM, White KL, Murrell JC.Buprenorphine, a μ-agonist opioid, has recently been licensed for equine use, but butorphanol, a κ-agonist opioid, is more commonly used in horses. The effect of the 2 opioids has not previously been compared in a large clinical study. Objective: To compare post operative analgesia and physiological variables in horses undergoing elective surgery following premedication with either buprenorphine or butorphanol in a conventional clinical setting. Methods: Multicentre, prospective, randomised, blinded clinical investigation. Methods: Eighty-nine healthy horses admitted for elective surgery to ...
Wang CC, Hartmann-Fischbach P, Krueger TR, Wells TL, Simonson A, Compton JC.Due to opiorphin's analgesic and antidepressant functions, its illicit use is rumored in some racing jurisdictions. Opiorphin is very difficult to detect due to its hydrophilic nature and rapid degradation in plasma and urine samples. METHODOLOGY & RESULTS: We have developed a sensitive, reliable method for opiorphin detection and confirmation in equine samples, using EDTA to inhibit analyte degradation between the time of collection and analysis. Opiorphin was extracted by weak cation exchange followed by analysis using HILIC-MS/MS. The method was validated and the LOD was determined to b...
Hertzsch R, Emmerich IU, Lachenmeier DW, Sproll C, Monakhova YB, Aboling S, Bachmann U, Vervuert I.Opioid alkaloids were identified in the urine of horses during an anti-doping control and in a case of intoxication. In both cases, it was suspected that the horses had ingested poppy-contaminated feed. To verify this suspicion, possible opioid alkaloid sources in Germany were identified through a literature research. Additionally, the contaminated feed was botanically and chemically analysed. The results indicated that both cases were most probably caused by the poppy in the feed. This highlights the previously underestimated risk of an intake of poppy-contaminated feed in horses. Recommendat...
Carregaro AB, Freitas GC, Ribeiro MH, Xavier NV, Dória RG.Continuous-rate infusion (CRI) of drugs results in more stable plasma drug concentrations than administration of intermittent boluses, thus providing greater stability of physiological parameters. The aim of this study was to evaluate the physiologic and analgesic effects of the administration of morphine, butorphanol, tramadol or methadone by CRI in horses with induced synovitis of the radiocarpal joint. Results: Increased values of cardiorespiratory parameters and body temperature were observed in all groups after initiation of opioid administration, and these increases were sustained throug...
Ohta M, Wakuno A, Okada J, Kodaira K, Nagata S, Ito M, Oku K.To evaluate the effects of IV fentanyl administration on the end-tidal sevoflurane concentration (ET(SEVO)) in thoroughbred racehorses, the ET(SEVO) required for internal fixation of longitudinal fractures was compared between horses anesthetized with sevoflurane-fentanyl (Group SF; n=9) and those anesthetized with sevoflurane alone (Group S; n=9). The loading dose of fentanyl (5.0 µg/kg) was administered over 15 min followed by a maintenance dose of fentanyl (0.1 µg/kg/min) throughout the operation in Group SF. The mean ET(SEVO) during the operation in Group SF (2.6 ± 0.2%) was significant...
Nogueira GP, Barnabe RC.Thoroughbred fillies were divided into three groups according to age: group 1, 7 fillies aged 1 to 2 years (G1) starting the training program; group 2, 9 fillies aged 2 to 3 years (G2) in a full training program; group 3, 8 older fillies 3 to 4 years of age (G3) training and racing. Blood samples were collected weekly from July to December. Cortisol was quantified using a solid phase DPC kit. The intra- and interassay coefficients of variation were 12.5% and 15.65% and sensitivity was 1.9 +/- 0.2 nmol/l. The semester average of cortisol levels varied between groups: G1 = 148.8 +/- 6.7, G2 = 12...
Kohn CW, Muir WW.Comparison of the visceral analgesic effects of xylazine, morphine, butorphanol, pentazocine, meperidine, dipyrone, and flunixin in a cecal distention model of colic pain indicated that xylazine produces the most relief from abdominal discomfort. Repeated administration of xylazine may reduce visceral pain so effectively that the seriousness of abdominal disease is obscured. Xylazine decreased propulsive motility in the jejunum and pelvic flexure of healthy ponies. Morphine and butorphanol also gave relief from visceral pain in the cecal distention model. Morphine may inhibit colonic, and buto...
Hamra JG, Kamerling SG, Wolfsheimer KJ, Bagwell CA.Diurnal variation in nociceptive sensitivity and plasma immunoreactive beta-endorphin (ir-BEND) concentrations was examined in eight healthy Thoroughbred horses. Pain thresholds, ir-BEND concentrations, rectal temperature, heart rate, respiratory rate and pupil diameter were measured over a 24 hour period. Nociceptive sensitivity was determined using two objective measures of pain: the skin-twitch reflex latency and the hoof withdrawal reflex latency. Significant variation in both nociceptive thresholds and ir-BEND concentrations were noted over the 24 hour period, with elevated pain threshold...
Clark JO, Clark TP.Critical to reducing patient morbidity as well as heightened ethical awareness, alleviation of pain in animals has become integral to medical case management and surgical procedures. Pharmacotherapy is directed at peripheral nociceptors, primary and secondary spinal neurons, and pain-processing areas in the CNS. Accordingly, three primary pharmacologic strategies have evolved: drugs that bind to and activate opioid receptors, drugs that bind to and activate alpha 2 receptors, and drugs that reduce de novo prostaglandin synthesis. In horses, the two predominant types of pain encountered are mus...
Tessier C, Pitaud JP, Thorin C, Touzot-Jourde G.There are no data investigating the effect of systemic morphine on the size of the stomach or the food consumption in horses. Objective: To evaluate gastrointestinal side effects of morphine administered systemically in healthy horses by the means of clinical and ultrasonographic evaluations. Methods: In vivo experiment. Methods: On day 1 of the experiment, six healthy French Trotter mares were evaluated clinically and an abdominal ultrasonography was performed three times 4Â h apart to record the size of the stomach, the number of contractions per minute of the duodenum, jejunum, caecum, left...
Muir WW, Skarda RT, Sheehan WC.The cardiopulmonary effects of the narcotic agonists morphine, meperidine, oxymorphone, and methadone and of the partial agonist pentazocine were examined in the pain-free adult horse. The drugs produced dysphoric followed by euphoric effects. Increases in heart rate, arterial blood pressure, and cardiac output were observed in all horses with all drugs. Arterial blood pressure remained increased even after heart rate and cardiac output had returned to base-line values. Respiratory rate generally remained unchanged or increased shortly after drug administration and then decreased insignificant...
Poller C, Hopster K, Rohn K, Kästner SB.Aim of the study was to compare the effect of neuroleptic sedation with acepromazine and neuroleptanalgesia with acepromazine and buprenorphine on thermal thresholds (TT) obtained at the nostrils and at the withers. The study was carried out as a randomized, blinded, controlled trial with cross-over design. Thermal thresholds were determined by incremental contact heat applied to the skin above the nostril (N) or the withers (W). Eleven horses were treated with saline (S), acepromazine (0.05 mg/kg) (ACE) or acepromazine and buprenorphine (0.0075 mg/kg) (AB) intravenously (IV). Single stimula...
Rigotti C, De Vries A, Taylor PM.A prospective, randomised, blinded, clinical trial in 47 ponies compared butorphanol and buprenorphine administered intravenously with detomidine prior to castration under anaesthesia. Detomidine 12 μg/kg intravenously was followed by butorphanol 25 μg/kg (BUT) or buprenorphine 5 μg/kg (BUP) before induction of anaesthesia with intravenous ketamine and diazepam. Quality of sedation, induction and recovery from anaesthesia, response to tactile stimulation, and surgical conditions were scored. If anaesthesia was inadequate 'rescue' was given with intravenous ketamine (maximum three dose...
Frigerio MA, Gómez Cisneros D, Santiago Llorente I, Manso-DÃaz G, López-Sanromán J.Chemical restraint is often used to perform diagnostic and minor surgical procedures; α2 -adrenoceptor agonists are the most commonly used drugs; however, the combination with an opiate can induce a profound sedation. There is a lack of kinematic studies examining the effects of the combination of these drugs on locomotor patterns. Objective: The objective of the study was to evaluate the duration of the effects of sedation with detomidine and detomidine combined with a low dose of butorphanol on the movement patterns of horses. Methods: The study was a controlled, randomised, blinded and cro...
Carregaro AB, Freitas GC, Ribeiro MH, Xavier NV, Dória RG.Continuous-rate infusion (CRI) of drugs results in more stable plasma drug concentrations than administration of intermittent boluses, thus providing greater stability of physiological parameters. The aim of this study was to evaluate the physiologic and analgesic effects of the administration of morphine, butorphanol, tramadol or methadone by CRI in horses with induced synovitis of the radiocarpal joint. Results: Increased values of cardiorespiratory parameters and body temperature were observed in all groups after initiation of opioid administration, and these increases were sustained throug...
Risberg ÅI, Spadavecchia C, Ranheim B, Hendrickson EH, Lervik A, Haga HA.To elicit and evaluate the NWR (nociceptive withdrawal reflex) in 2 and 11 day old foals, to investigate if buprenorphine causes antinociception and determine if the NWR response changes with increasing age. The effect of buprenorphine on behaviour was also evaluated. Methods: Prospective, experimental cross-over trial. Methods: Nine Norwegian Fjord research foals. Methods: Buprenorphine, 10 μg kg(-1) was administered intramuscularly (IM) to the same foal at 2 days and at 11 days of age. The NWR and the effect of buprenorphine were evaluated by electromyograms recorded from the left deltoid m...
Albrizio M, Lacalandra GM, Micera E, Guaricci AC, Nicassio M, Zarrilli A.Opioid receptors and endogenous opioid peptides act not only in the control of nociceptive pathways, indeed several reports demonstrate the effects of opiates on sperm cell motility and morphology suggesting the importance of these receptors in the modulation of reproduction in mammals. In this study we investigated the expression of delta opioid receptors on equine spermatozoa by western blot/indirect immunofluorescence and its relationship with sperm cell physiology. Methods: We analyzed viability, motility, capacitation, acrosome reaction and mitochondrial activity in the presence of naltri...
Sheehy JG, Hellyer PW, Sammonds GE, Mama KR, Powers BE, Hendrickson DA, Magnusson KR.To evaluate mu-opioid receptors in synovial membranes of horses and determine whether these receptors are up-regulated in nerve endings during inflammation. Methods: Synovial tissue obtained from 39 client-owned horses during arthroscopy and 14 research horses during necropsy; brain and synovial tissues were obtained during necropsy from 1 horse, and control tissues were obtained from a mouse. Methods: Horses were classified into 7 groups on the basis of histologically determined degree of inflammation. Binding of primary rabbit antibody developed against mu-opioid receptors in equine synovial...
Hellyer PW, Bai L, Supon J, Quail C, Wagner AE, Mama KR, Magnusson KR.To test the hypothesis that the distribution, density, and subtype of opioid and alpha (alpha)-2 adrenergic receptors within the central nervous system (CNS) are significantly different between horse and dog. Methods: Prospective experimental study. Methods: Three dogs (3 years of age) and three horses (2-5 years of age). Animals were opioid- and alpha-2 agonist-free at the time of euthanasia. Methods: Brain tissue was obtained at 126 days post-surgery from dogs and 72 days post-surgery from horses. The brains were removed, sectioned coronally into 1-cm slabs, frozen in methylbutane, which was...
Emanuel D, Kästner SBR, Delarocque J, Grob AJ, Bienert-Zeit A.The aim of this prospective clinical trial was to compare the influence of butorphanol, buprenorphine and levomethadone on sedation quality and postoperative analgesia in horses undergoing cheek tooth extraction. Fifty horses were assigned to three groups prior to oral cheek tooth extraction. Horses were treated with acepromazine, followed by a detomidine bolus, one of the three opioids and both a nerve block and gingival anaesthesia. During the surgery, sedation was maintained with a detomidine constant rate infusion. After surgery, the quality of sedation, surgical conditions and severity of...
Albrizio M, Guaricci AC, Maritato F, Sciorsci RL, Mari G, Calamita G, Lacalandra GM, Aiudi GG, Minoia R, Dell'Aquila ME, Minoia P.The development of fertilizing ability in sperm cells is associated with changes in the plasma membrane. However, to date the exact nature of sequentially activated primary receptors and channels and the signal transduction pathways derived from these remains elusive. We analyzed the expression and localization of the mu-opioid receptor in equine spermatozoa. A transcript corresponding to the third extracellular loop that selectively binds mu agonists was amplified, sequenced and compared with the known sequences in humans, rats and cattle. The amplification product showed a high degree of nuc...
Lizarraga I, Castillo-Alcala F.Combinations of α2 -adrenoceptor and opioid agonists are commonly used in equids, but little scientific information is available on donkeys. Objective: To compare the sedative and hypoalgesic effects of xylazine alone or in combination with different dosages of butorphanol in donkeys. Methods: Placebo-controlled, operator-blinded, randomised, crossover, Latin square study. Methods: Six donkeys received intravenous normal saline and normal saline (NS-NS); xylazine (0.5 mg/kg bwt) and normal saline (X-NS); xylazine and 10 μg/kg bwt butorphanol (X-B10); xylazine and 20 μg/kg bwt butorpha...
Natalini CC, Robinson EP.Heart rate, arterial blood pressures, respiratory rate, body temperature, and central nervous system excitement were compared before and after epidural administration of morphine (0.1 mg/kg), butorphanol (0.08 mg/kg), alfentanil (0.02 mg/kg), tramadol (1.0 mg/kg), the k-opioid agonist U50488H (0.08 mg/kg), or sterile water using an incomplete Latin square crossover design in five conscious adult horses. Treatments were administered into the first intercoccygeal epidural space. Significant (P <.05) reductions in respiratory rate were detected after epidural administration of morphine, alfent...
Nurnberg HG, Keith SJ, Paxton DM.Treatment successes of various stereotyped behaviors in animals and humans has renewed interest in ethologic animal models for the study of psychiatric disorders. This report presents another such behavior occurring in horses to weaving. This anomalous, repetitive, and purposeless behavior draws analogies to human compulsive spectrum behaviors. A "weaver" provided an opportunity to evaluate serotonin, dopamine, and opioid neurotransmitter system contributions by probing each with a selective agent in A-B-A-C-A-D design. The horse was treated in sequential 1-month periods separated by 1-month w...
Love EJ, Lane JG, Murison PJ.To determine the effect of morphine administration on commonly monitored cardio-respiratory variables and recovery quality in horses undergoing anaesthesia and surgery. Methods: Prospective, randomized clinical study. Methods: Thirty-eight thoroughbred horses, 32 geldings and six mares, 3-13 years old, weighing 411-600 kg. Methods: A standard anaesthetic technique was used. Twenty minutes after induction of anaesthesia horses received 0.1 mg kg(-1) (0.1 m) or 0.2 mg kg(-1) (0.2 m) morphine by intravenous injection. A control group did not receive morphine. Heart rate, respiratory rate (fr), me...
Casella S, Giannetto C, Giudice E, Marafioti S, Fazio F, Assenza A, Piccione G.Adenosine diphosphate (ADP)-induced platelet aggregation in fed and fasted horses after addition of tramadol hydrochloride was evaluated in vitro. On 10 horses citrated blood samples were collected 2h after feeding (fed animals) and 21 h after feeding (fasted animals). Final concentrations of ADP 1 and 0.5 μM, and tramadol hydrochloride (1, 15, 30, 45 and 60 min after the addition of tramadol) were used to determine the maximum degree and initial velocity of platelet aggregation. Repeated measures multifactor analysis of variance (MANOVA) was used to evaluate the effect of feeding/fasting con...
Dhanjal JK, Wilson DV, Robinson E, Tobin TT, Dirikolu L, Dirokulu L.To determine the optimal dose, serum concentrations and analgesic effects of intravenous (IV) tramadol in the horse. Two-phase blinded, randomized, prospective crossover trial. Seven horses (median age 22.5 years and mean weight 565 kg). Horses were treated every 20 minutes with incremental doses of tramadol HCl (0.1-1.6 mg kg(-1)) or with saline. Heart rate, respiratory rate, step frequency, head height, and sweating, trembling, borborygmus and head nodding scores were recorded before and up to 6 hours after treatment. In a second study, hoof withdrawal and skin twitch reflex latencies (HWRL ...
Dell'Aquila ME, Albrizio M, Guaricci AC, De Santis T, Maritato F, Tremoleda JL, Colenbrander B, Guerra L, Casavola V, Minoia P.The micro-opioid receptor (MOR) was identified in equine oocytes, cumulus and granulosa cells. By RT-PCR, a 441bp fragment was observed. By immunoblotting, a 65 kDa band was detected in samples of winter anestrous whereas in cells recovered in breeding season, two bands, 65 and 50 kDa, were found. The 65 kDa band was significantly more intense in winter anestrous specimens. In samples recovered in the breeding season, this band significantly decreased with the raise of follicle size and was heavier in compact oocytes and cumulus cells. The protein was localized on the oolemma and within the cy...
Pascoe PJ, Taylor PM.To determine whether specific dopamine receptor antagonists block alfentanil-induced locomotor stimulation in horses. Methods: Randomized, prospective, crossover experiment. Methods: Eight adult horses (462-604 kg). Methods: Doses of dopamine-1 (D1) (NNC 01-0756) and dopamine-2 (D2) antagonists (eticlopride) were selected in a pilot study prior to a three part, blinded, cross-over study. In part 1, horses received 7.5 micro g kg-1 eticlopride, 5 micro g kg-1 NNC 01-0756 or an equal volume of saline. In part 2, they received both antagonists and in part 3, acepromazine at 0.05 mg kg-1. Locomoto...
Roberts MC, Argenzio A.Amitraz, atropine, glycopyrrolate and morphine (but not its derivatives, meperidine [pethidine], oxymorphone and butorphanol) produced similar effects on clinically observed intestinal functions and significantly prolonged intestinal transit, as assessed with polyethylene glycol (PEG). However, their mechanisms of action, particularly on intestinal transport (fluid movement), may differ widely. Loperamide appeared to exert a preferential action on intestinal transport rather than motility, as there was no significant delay in PEG transit. The action of amitraz in perturbing smooth muscle coord...
Guedes AG, Knych HK, Soares JH, Brosnan RJ.This study evaluated the pharmacokinetics and physiological effects of tramadol during repeated oral administrations in horses. Nine adult healthy horses were administered tramadol at 5 and 10Â mg/kg orally every 12Â h for 5Â days in a randomized, crossover design with a 3-week washout between treatments. Plasma concentrations of tramadol, O- and N-desmethyltramadol (M1 and M2) were measured using Liquid-Chromatography-Mass Spectrometry at predetermined time points following each tramadol administration. Cardiovascular, respiratory and gastrointestinal physiological variables were monitored an...
Hemmings A, Parker MO, Hale C, McBride SD.Spontaneous stereotypic behaviours are repetitive, compulsive, topographically invariant response patterns commonly observed in captive or domestic animals, which have been linked to dysfunction of basal ganglia input/output pathways. There is evidence that endogenous opioids play a key regulatory role in basal ganglia direct and indirect pathways, but their precise role, both causally and functionally, in spontaneous stereotypic behaviour is unclear. Here we examined the profile of mu- and delta-opioid receptors (density [Bmax] and affinity [Kd]) of basal ganglia structures in stereotypy (nâ€...
Louro LF, Milner PI, Bardell D.Opioid epidural analgesia has been shown to provide effective analgesia in horses. There is a lack of evidence regarding the effect of opioid epidural analgesia on quality of recovery in horses. Objective: Identify whether opioid epidural analgesia influences quality of recovery in horses undergoing general anaesthesia required for management of hindlimb synovial sepsis. Methods: Single-centre retrospective cross-sectional study. Methods: Data were obtained from the clinical records of horses which had undergone arthroscopic or tenoscopic surgery for management of hindlimb synovial sepsis over...
