Evaluation of the interaction of mu and kappa opioid agonists on locomotor behavior in the horse.

This study was designed to determine the interactive effects of mu and kappa opioid agonists on locomotor behavior in the horse. Three doses of a mu agonist, fentanyl (5, 10, 20 micrograms/kg) and a kappa agonist U50,488H (30, 60, 120 micrograms/kg) were administered in a random order to six horses. Locomotor activity was measured using a two minute footstep count. Each dose of U50,488H was then combined with 20 micrograms/kg of fentanyl to determine the interactive effects of the drugs on locomotor activity. A significant increase in locomotor activity was seen with 20 micrograms/kg of fentanyl and all the drug combinations. The combination of U50,488H with fentanyl resulted in an earlier onset of locomotor activity. At the highest doses of the combination (U50,488H 120 micrograms/kg, fentanyl 20 micrograms/kg), the duration of locomotor activity was significantly increased when compared to the other doses. We conclude that locomotor activity is maintained or enhanced in horses when a receptor specific kappa agonist is combined with a mu receptor agonist.     

Pharmacodynamic evaluation of the peripheral pain inhibition by carprofen and flunixin in the horse

Carprofen, flunixin meglumine and placebo in the form of a physiological solution of sodium chloride were tested in an open randomised cross-over trial for analgesic efficacy in horses with two external skin-stimulation systems. Both systems, the withers model and the "heating element" model, were compared in order to find an optimal way to measure pain perception after stimulating the skin with high temperature. No analgesic effect of flunixin or carprofen could be demonstrated when using the withers model. In the "heating element" model, a 1.1 mg/kg i.v. dose of flunixin meglumine failed to inhibit the peripheral pain, while it could be shown that a 0.7 mg/kg i.v. dose of carprofen inhibited the peripheral perception of pain in horses for approximately 24 hours after the drug injection. To induce an analgesic effect with carprofen, its plasma concentration had to be at least 1.5 micrograms/ml.     

Pharmacology of narcotic analgesics in the horse: selective blockade of narcotic-induced locomotor activity

The locomotor responses of horses given morphine and fentanyl were blocked or lessened by administration of naloxone or acepromazine. Naloxone given at the dosage of 0.015 mg/kg completely blocked the locomotor activity induced in horses given fentanyl (0.020 mg/kg of body weight). The locomotor stimulation produced by morphine given at the dosage of 2.4 mg/kg was reduced by 75% of naloxone (0.020 mg/kg). Acepromazine partially blocked the locomotor responses to fentanyl and morphine. This blockade activity reached its peak about 30 minutes after acepromazine was given (IV) and lasted more than 6 hours. Simultaneous administration of acepromazine and morphine was associated with substantial respiratory depression for more than 4 hours after administration of both drugs. In other experiments, fentanyl did not add to the partial locomotor response observed after large doses of pentazocine were given--this being consistent with the concept that pentazocine possesses both antagonist and agonist actions at the narcotic receptor. Furosemide and phenylbutazone, given at usually used clinical doses, had no effect on the locomotor response to fentanyl, indicating that the usual clinical dosages of neither drug exerted stimulant or depressant actions.     

Transdermal fentanyl combined with nonsteroidal anti-inflammatory drugs for analgesia in horses

This study investigated the pharmcokinetics, efficacy, and safety of the fentanyl transdermal therapeutic system (TTS) in horses in which there was an inadequate analgesic response to nonsteroidal anti-inflammatory drugs (NSAIDs) alone. Nine horses with pain that was refractory to therapeutic doses of phenylbutazone (n = 3) or flunixin meglumine (n = 6) subsequently also received between 39 and 110 microg/kg of transdermal fentanyl. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 60, and 72 hours after patch application, and a radioimmunoassay was used to determine serum fentanyl concentrations. Pharmacokinetic values were determined by noncompartmental analysis. Physical examination findings were recorded in all horses, and pain and lameness grading systems were used to assign scores to 8 and 6 horses, respectively. All horses tolerated the administration of fentanyl TTS, in that no clinically significant adverse effects attributable to fentanyl were observed. Use of the TTS resulted in variable serum concentrations of fentanyl, with a peak serum concentration of 2.2+/-1.1 ng/mL (mean+/-SD) and a time to peak serum concentration of 26+/-13 hours. After transdermal fentanyl administration, mean time to reach serum fentanyl concentrations consistent with analgesia in other species (1 ng/mL) was 14 hours. In addition, serum fentanyl concentrations of 1 ng/mL or greater were maintained in all but one horse for at least 18 hours. Pain scores were significantly decreased after fentanyl TTS and NSAID administration (P < .05), but lameness scores were not significantly different (P > .05). Overall, administration of fentanyl TTS had a favorable pharmacokinetic profile in horses with clinical pain, and the fentanyl TTS in combination with NSAIDs appeared to provide safe and effective analgesia in most of the horses with pain that was refractory to NSAID therapy alone.     

Pharmacokinetics of fentanyl following intravenous and transdermal administration in horses

REASONS FOR PERFORMING STUDY: Although fentanyl has been reported to cause CNS excitation in horses, a transdermal therapeutic system (TTS) containing this mu agonist has recently been used empirically in equine medicine to treat moderate to severe pain. A better understanding of the disposition of fentanyl following transdermal administration would facilitate the clinical use of TTS fentanyl to obtain analgesia in horses. OBJECTIVES: To determine the pharmacokinetics of fentanyl following i.v. and TTS patch administration in healthy, mature horses and to evaluate the tolerance of horses to TTS fentanyl administration. METHODS: The pharmacokinetics of fentanyl in serum were assessed following a single i.v. dose, a single TTS dose, and multiple TTS doses in 6 healthy horses. Physical examinations, haematology and serum biochemistry analyses during transdermal fentanyl application were then performed to determine tolerance of continuous fentanyl administration. RESULTS: Fentanyl was very rapidly and completely absorbed following a single TTS dose. Mean serum fentanyl concentrations consistent with analgesia in other species were reached by 1 h and maintained until 32 h after patch application. Similar steady state serum concentrations were obtained when multiple doses of TTS fentanyl were administered every 48 or 72 h over 8 or 9 days, with less fluctuation in serum concentrations during the 48 h dosing interval. Three horses exhibited brief (< 12 h) episodes of increased body temperature; however, transdermal fentanyl administrations were not associated with other significant changes in haematology and biochemistry panels or physical examination findings. CONCLUSIONS AND POTENTIAL RELEVANCE: Although the pharmacodynamics of fentanyl have not been investigated fully in horses, transdermally-administered fentanyl exhibited a favourable pharmacokinetic profile without clinically relevant side effects and may be a useful analgesic in equine patients.     

Use of opioids for pain and anesthetic management in horses.

REGIONAL ADMINISTRATION: There is limited, but convincing, evidence that epidural administration of morphine and some other mu-agonist opioids consistently relieves regional pain in horses. In addition, this effect is not accompanied by notable undesirable effects. On the other hand, a clinically important analgesic action has not been demonstrated for similarly administered kappa-agonist opioids. There has been little objective data presented to support the analgesic effectiveness of intra-articularly administered opioids in horses. However, the evidence of local opioid receptors legitimately encourages work to substantiate the value of intra-articular opioid administration to relieve joint-associated pain in horses. SYSTEMIC ADMINISTRATION: So far, study results do not provide convincing, objective evidence to support the opinion that systemically administered opioids consistently and effectively relieve pain in horses. Given this lack of evidence, and considering that opioids stimulate locomotor and other forms of unwanted excitant behavior, reduce propulsive gastrointestinal motility, decrease alveolar ventilation (especially in association with general anesthesia), and require regulatory and practical considerations for abuse potential in both humans and horses, we conclude that routine, indiscriminate administration of opioids for pain relief in horses is not justified. Identification and focused, objective study of selective beneficial opioid actions to provide guidance for appropriate clinical use is long overdue.     

Reduction of isoflurane MAC by fentanyl or remifentanil in rats

Objective The main objective of the study was to determine the effects of three different infusion rates of fentanyl and remifentanil on the minimum alveolar concentration (MAC) of isoflurane in the rat. A secondary objective was to assess the cardiovascular and respiratory effects of the two opioid drugs. Animal population Thirty‐seven male Wistar rats were randomly allocated to one of six treatment groups. Material and methods For all treatment groups anaesthesia was induced with 5% isoflurane in oxygen using an induction chamber. A 14‐gauge catheter was used for endotracheal intubation, and anaesthesia was maintained with isoflurane delivered in oxygen via a T‐piece breathing system. A baseline determination of the minimum alveolar concentration of isoflurane (MAC_ISO) was made for each animal. Fentanyl (15, 30, 60 µg kg^?1 hour^?1) or remifentanil (60, 120, 240 µg kg^?1 hour^?1) were infused intravenously into a previously cannulated tail vein. Thirty minutes after the infusion started, a second MAC_ISO (MAC_ISO+drug) was determined. The carotid artery was cannulated to monitor the arterial pressure and to take samples for arterial gas measurements. Cardiovascular (heart rate and arterial pressure) and respiratory (respiratory rate and presence/absence of apnoea) effects after opioid infusion were also recorded. Results Fentanyl (15, 30, 60 µg kg^?1 hour^?1) and remifentanil (60, 120, 240 µg kg^?1 hour^?1) similarly reduced isoflurane MAC in a dose‐dependent fashion: by 10% at lower doses, 25% at medium doses and by 60% at higher doses of both the drugs. Both opioids reduced the respiratory rate in a similar way for all doses tested. No episodes of apnoea were recorded in the remifentanil groups, while administration of fentanyl resulted in apnoea in three animals (one at each dose level). The effects on the cardiovascular system were similar with both drugs. Conclusions We conclude that the intraoperative use of remifentanil in the rat reduces the MAC of isoflurane, and that this anaesthetic sparing effect is dose‐dependent and similar to that produced by fentanyl at the doses tested. Clinical relevance The use of remifentanil during inhalant anaesthesia in the rat can be considered an intravenous alternative to fentanyl, providing similar reduction in isoflurane requirements. Due to its rapid offset, it is recommended that alternative pain relief be instituted before it is discontinued.     

Effect of fentanyl on visceral and somatic nociception in conscious horses

BACKGROUND: Transdermal fentanyl is used clinically in horses based on pharmacokinetic data and antinociceptive effects documented in other species. HYPOTHESIS: Fentanyl IV administration increases both visceral and somatic nociceptive threshold in conscious horses. ANIMALS: Six clinically normal horses, each fitted with a permanent gastric cannula. METHODS: Visceral nociception was evaluated with 2 methods of threshold detection--olorectal distention and duodenal distention. Somatic nociception was assessed by measurement of thermal threshold. Fentanyl was administered as an increasing stepwise infusion followed by a continuous-rate infusion for a total of 2 hours. There were 4 doses of fentanyl and 1 dose each of saline and xylazine administered to each horse. Serum fentanyl concentrations were measured and the resulting data were used to determine pharmacokinetic parameters for each horse. All data were analyzed by means of a 3-factor analysis of variance followed by either a simple t test or a Bonferroni t test for multiple comparisons. RESULTS: Fentanyl administration did not result in significant changes in duodenal or colorectal distention threshold. Thermal threshold showed an increased trend at the 15-minute time point for the highest fentanyl group only, with a corresponding mean serum fentanyl concentration of 7.82 +/- 2.10 ng/mL. Two horses in this group became agitated and tachycardic during the first 15 minutes of the infusion. CONCLUSIONS AND CLINICAL IMPORTANCE: Fentanyl did not produce a significant antinociceptive effect at the doses used, 2 of which resulted in serum concentrations above the nociceptive threshold in other species.     

Behavioral and Antinociceptive Effects of Alfentanil,Butorphanol, and Flunixin in Horses

To determine the behavioral and antinociceptive effects of narcotic and non-narcotic analgesics administered by intravenous injection in horses, 10 thoroughbred mares weighing between 450 and 550 kg and ranging in age from 8 to 13 years old were analyzed. The effects of alfentanil, butorphanol, flunixin, and saline solution on the general activity of the horses were investigated by measuring spontaneous locomotor activity (SLA) and head height (HH) in two behavior stalls. The antinociceptive effects of alfentanil (0.02 mg kg⁻¹), butorphanol (0.1 mg kg⁻¹), flunixin meglumine (0.5 mg kg⁻¹), and saline were determined by measuring skin twitch reflex latency (STRL) after thermal cutaneous nociceptive stimulation. A paired Student t-test was used to compare SLA and HH between the groups of horses receiving different doses of the same drug at various time points. The Tukey test was used to compare the antinociceptive effect of the treatments. Differences were considered significant when P value was <.05. Horses treated with opioid analgesics demonstrated excitation, as shown by a significant increase in SLA at all doses tested and by neighing and demonstrating attentive attitudes with movement of the ears, stereotypical walking, and ataxia in most of the animals. HH was elevated only in animals treated with alfentanil. Antinociception was observed at 5 and 30 minutes after administration of alfentanil and butorphanol, respectively. Increased SLA was observed at 30 and 90 minutes after administration of alfentanil and butorphanol, respectively. We observed no effect on antinociception in horses given flunixin. In conclusion, this study suggests that alfentanil has a faster onset and a shorter duration than butorphanol; however, both drugs are able to stimulate the central nervous system.     

Induction of Noninflammatory Pain in an Experimental Foot Lameness Model in Horses

The mechanism by which nonsteroidal anti-inflammatory drugs mitigate pain caused by a heart bar shoe (HBS) model of lameness is unknown. The purpose of this study was to determine if this HBS model of lameness induces inflammation in horses. Five healthy adult horses from a university teaching herd were enrolled. A custom HBS was applied to the left front foot of each horse, followed by induction of the American Association of Equine Practitioners Lameness Score of 4. Inflammatory markers including serum amyloid A (SAA) concentration, local venous tumor necrosis factor alpha and prostaglandin E2 (PGE2) concentrations, and foot temperature were measured before lameness induction and 1, 3, and 13 hours after lameness induction. Lameness induction using the HBS model did not significantly increase production of plasma SAA, tumor necrosis factor alpha, or PGE2 concentrations at measured time points. Immediately and 1 hour after lameness induction, dorsal coronary band temperatures were higher in the left front foot compared with the right front foot, but there was no difference at 3 or 13 hours. In conclusion, the HBS model did not induce inflammation as assessed by select inflammatory markers, suggesting that the HBS model induces mechanical rather than inflammatory pain. This should be considered when using the HBS model to assess analgesic drugs in horses.     

Comparison of behavioral effects of morphine and fentanyl in dogs and cats

Behavioral effects induced by intravenous administration of morphine at 0.3, 0.6, 1.2, and 2.4 μg/kg and fentanyl at 5, 10, 20, and 40 μg/kg were evaluated in dogs and cats. In dogs, fentanyl and morphine depressed activity and level of consciousness in a dose- dependant manner. In cats, higher doses of fentanyl stimulated activity temporarily, but excitement, so-called "opioid mania," was not observed. Morphine induced distinctive behavioral changes characterized by sitting with fixed staring, and "opioid mania" was not observed in cats.     

Epidural anesthesia and analgesia in horses.

Intercoccygeal, or caudal, epidural injection of local anesthetics is a convenient method of producing analgesia and local anesthesia of the tail and perineal structures in conscious standing horses. This technique has been further developed to provide long duration analgesia and anesthesia by placement of catheters into the epidural space of horses. More recently, opioid, alpha-2 adrenergic agonists, ketamine and other analgesic agents have been administered by caudal epidural injection, providing pain relief in both conscious, standing and anesthetized, recumbent horses. This chapter describes the development of different anesthetic and analgesic epidural techniques in horses, methods for epidural injection and catheterization, and reviews the current literature related to epidural analgesia and pain control in horses.     

Analgesia.

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 musculoskeletal and visceral pain. Several factors must be considered when devising a therapeutic strategy, including the etiology of the painful event, desired duration of therapy (acute vs chronic), desire for sedation, and potential side effects and toxicity. Opioids and alpha 2 agonists are particularly effective for visceral pain associated with colic. Butorphanol remains the only commercially available opioid and provides superior visceral analgesia compared with pentazocine or flunixin meglumine but not compared with the alpha 2 agonists. The behavioral changes such the sedative effects of alpha 2 agonists and the increased locomotion and CNS excitability seen with some opioids are important considerations when these agents are used as analgesics. NSAIDs may be considered for visceral pain therapy also, especially pain associated with an inflammatory component or endotoxemia. In particular, flunixin meglumine and ketoprofen provide prolonged analgesia and suppress the effects of endotoxin. Long-term therapy of musculoskeletal diseases usually necessitates chronic NSAID use. Although many NSAIDs are now available in approved equine formulations, there remain some important differences among NSAIDs for the practitioner to consider when choosing an analgesic. NSAIDs differ in their ability to ameliorate pyrexia, affect platelet function, alleviate pain, and reduce inflammation. For ease of administration, those available for oral use include phenylbutazone, meclofenamic acid, flunixin meglumine, and naproxen. All are potentially ulcerogenic, and poor tolerance to one may necessitate switching to another with a better toleration profile or to drug from a different analgesic class.     

Objective tests of analgesic drugs in ponies

An equine model, subjected to three kinds of pain (superficial, deep, and visceral) was used to test effects of analgesic drugs. Two groups of ponies were used. In the first group of six ponies, six drugs (fentanyl, meperidine, methadone, oxymorphone, pentazocine, and xylazine) were given according to a Latin square experimental design, and tests were made at 30-minute intervals for 4 hours. Mean values (control) for the three kinds of pain were obtained before and after the tests and were compared with the mean values (drugs) obtained over 2- and 4-hour intervals (four and eight measurements per interval, respectively). Xylazine was significantly more effective in obtunding deep pain (P less than 0.05) at 2- and 4-hour intervals than were the other drugs. Significant differences were not found between values for controls and values for drugs tested for relief of superficial and visceral pain at 2- and 4-hour intervals. In the second group of four ponies, the drug (xylazine) determined most effective in group 1 ponies was given alone or in combination with the next most effective drugs (fentanyl, meperidine, and oxymorphone). Data were obtained in the same manner as for the first group. Mean values were calculated for 2- and 4-hour intervals, and the variance was analyzed. Xylazine and fentanyl combined had the best 2- and 4-hour performance for the relief of visceral pain in the second group (P less than 0.1). Neither xylazine nor a combination of drugs differed markedly from control values for 2- and 4-hour intervals for relief of superficial and deep pain.     

Pain associated with the sacroiliac joint region: a clinical study of 74 horses

REASONS FOR PERFORMING STUDY: There has been no large study of horses with suspected sacroiliac (SI) joint region pain in which the clinical diagnosis has been supported by either abnormal radiopharmaceutical activity in the SI joint region or by periarticular infiltration of local anaesthetic solution. OBJECTIVES: To describe the clinical features of horses with SI joint region pain, to document the age, breed, sex, discipline, size and conformation of affected horses and to compare these with the author's (SD) normal case population and to document the results of infiltration of local anaesthetic solution around the SI joint region. METHODS: Horses were selected for inclusion in the study based upon the exclusion of other causes of lameness or poor performance, together with clinical signs suggestive of SI joint pain and abnormal radiopharmaceutical activity in the SI joint region and/or a positive response to periarticular infiltration of local anaesthetic solution. RESULTS: Sacroiliac joint region disease was identified in 74 horses between November 1997 and March 2002. Dressage and showjumping horses appeared to be at particular risk (P < 0.001). Affected horses were generally slightly older than the normal clinic population (P < 0.0001), taller at the withers (P < 0.0001) and of greater bodyweight (P < 0.01). There was a significant effect of breed (P < 0.001), with a substantially higher proportion of Warmblood horses (51%) in the SI pain group compared to the normal clinic population (29%). There was no correlation between conformation and the presence of SI joint region pain. The tubera sacrale appeared grossly symmetrical in most (95%) horses. Poor development of the epaxial muscles in the thoracolumbar region and asymmetry of the hindquarter musculature were common. Twenty-six horses (35%) showed restricted flexibility of the thoracolumbar region and 10 (16%) had an exaggerated response to pressure applied over the tubera sacrale. Fourteen horses (19%) were reluctant to stand on one hindlimb for prolonged periods. The majority of horses (75%) had a straight hindlimb flight and only 18% moved closely behind or plaited. In all horses restricted hindlimb impulsion was the predominant feature; invariably this was most obvious when the horse was ridden. Stiffness, unwillingness to work on the bit and poor quality canter were common. Sacroiliac joint region pain was seen alone (47%), or in conjunction with thoracolumbar pain (16%), hindlimb lameness (20%), forelimb lameness (7%) or a combination of problems (10%). Seventy-three horses (99%) had abnormalities of the SI joint region identified using nuclear scintigraphy. Infiltration of local anaesthetic solution around the SI joint region produced profound improvement in gait in all 34 horses in which it was performed. CONCLUSIONS AND POTENTIAL RELEVANCE: Careful clinical examination combined with scintigraphic evaluation of the SI joint region and local analgesia can enable a more definitive diagnosis of SI joint region pain than has previously been possible.     

Influence of general anaesthesia on the pharmacokinetics of intravenous fentanyl and its primary metabolite in horses

REASONS FOR PERFORMING STUDY: In order to evaluate its potential as an adjunct to inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be determined. OBJECTIVES: To describe the pharmacokinetics of fentanyl and its metabolite, N-[1-(2-phenethyl-4-piperidinyl)maloanilinic acid (PMA), after i.v. administration of a single dose to horses that were awake in Treatment 1 and anaesthetised with isoflurane in Treatment 2. METHODS: A balanced crossover design was used (n = 4/group). During Treatment 1, horses received a single dose of fentanyl (4 microg/kg bwt, i.v.) and during Treatment 2, they were anaesthetised with isoflurane and maintained at 1.2 x minimum alveolar anaesthetic concentration. After a 30 min equilibration period, a single dose of fentanyl (4 microg/kg bwt, i.v.) was administered to each horse. Plasma fentanyl and PMA concentrations were measured at various time points using liquid chromatography-mass spectrometry. RESULTS: Anaesthesia with isoflurane significantly decreased mean fentanyl clearance (P < 0.05). The fentanyl elimination half-life, in awake and anaesthetised horses, was 1 h and volume of distribution at steady state was 0.37 and 0.26 l/kg bwt, respectively. Anaesthesia with isoflurane also significantly decreased PMA apparent clearance and volume of distribution. The elimination half-life of PMA was 2 and 1.5 h in awake and anaesthetised horses, respectively. CONCLUSIONS AND POTENTIAL RELEVANCE: Pharmacokinetics of fentanyl and PMA in horses were substantially altered in horses anaesthetised with isoflurane. These pharmacokinetic parameters provide information necessary for determination of suitable fentanyl loading and infusion doses in awake and isoflurane-anaesthetised horses.     

Pressure algometry to quantify muscle pain in racehorses with suspected sacroiliac dysfunction

REASONS FOR PERFORMING STUDY: Despite the prevalence of orthopaedic injuries to horses, there is no objective means of quantifying the intensity of musculoskeletal pain. HYPOTHESES: Mechanical nociceptive thresholds (MNT) can be measured repeatably by pressure algometry in horses and MNTs are correlated with both severity of clinical signs and subjective scores of muscle pain on palpation in horses with suspected sacroiliac dysfunction (SID). METHODS: The technique of pressure algometry and its repeatability was tested at 4 anatomical sites on either side of the thoracolumbar and pelvic region in 12 Thoroughbreds in training. In a second series of 15 racing Thoroughbreds, using a different set of landmarks, pain on palpation was assessed by pressure algometry. Horses were grouped based on clinical scores of SID as normal (n = 5), mild (n = 5), moderate (n = 4) and severe (n = 1) suspected SID and scored for muscle pain response by manual palpation. RESULTS: Pressure algometry was shown to be a repeatable measure of MNTs. Horses with suspected SID had significantly lower mean MNT when sites and horses were pooled and showed greater differences in mean algometer measurements between left and right sides, compared to control horses. A significant correlation was found between mean pressure algometry measurements and both suspected SID grade and muscle pain response on palpation. CONCLUSION AND POTENTIAL RELEVANCE: Horses with suspected SID displayed lower MNTs compared to control horses, especially in the pelvic region. This supports a potential role for pressure algometry in providing an objective means of quantifying musculoskeletal pain reflected as a reduced MNT associated with SID and its response to physiotherapy or other treatments.     

Intra‐articular opioid analgesia is effective in reducing pain and inflammation in an equine LPS induced synovitis model

Reasons for performing study: Intra‐articular administration of morphine as a local analgesic and anti‐inflammatory drug is widely used in human medicine. In equids, little is known about its clinical analgesic and anti‐inflammatory efficacy. Objectives: To use an inflammatory orthopaedic pain model to investigate the analgesic and anti‐inflammatory effects of intra‐articularly administered morphine as a new treatment modality in horses with acute arthritis. Methods: In a crossover study design, synovitis was induced in the left or right talocrural joint by means of intra‐articular injection of 0.5 ng lipopolyssacharide (LPS). The effect of 120 mg morphine, intra‐articularly administered at 1 h after induction of synovitis, was evaluated using both physiological and behavioural pain variables. Synovial fluid was sampled at 0, 4, 8, 28 and 52 h after induction of synovitis and analysed for total protein concentration, leucocyte count and for prostaglandin E₂, bradykinin and substance P concentrations by ELISA. Ranges of motion of metatarsophalangeal and talocrural joints were measured as kinematic variables with the horses walking and trotting on a treadmill under sound and lame conditions. Clinical lameness scores and several behavioural variables related to the perception of pain were obtained. Results: LPS injection caused marked transient synovitis, resulting in increased concentrations of inflammatory synovial fluid markers, clinical lameness, joint effusion and several behavioural changes, such as increased time spent recumbent, decreased limb loading at rest and decreased time spent eating silage. Intra‐articular morphine resulted in a significant decrease in synovial white blood cell count, prostaglandin E₂ and bradykinin levels and improvement in clinical lameness, kinematic and behavioural parameters, compared to placebo treatment. Conclusions: Intra‐articular morphine offers potent analgesic and anti‐inflammatory effects in horses suffering from acute synovitis. Potential relevance: Local administration of opioids may be useful for horses with acute inflammatory joint pain and offers possibilities for multimodal analgesic therapies without opioid‐related systemic side effects.     

Effect of local analgesia on movement of the equine back

REASONS FOR PERFORMING STUDY: Diagnostic infiltration of local anaesthetic solution is commonly used in cases of equine back pain. Evaluation is subjective and it is not known how local analgesia of the back affects horses without clinical signs of back pain. OBJECTIVES: To evaluate the effect of infiltration of local anaesthetics on the movement of the back in horses without clinical signs of back pain, and to evaluate the usefulness of kinematic studies as an objective and quantitative tool in evaluating local analgesia in clinical practice. METHODS: The kinematics of the back in 10 clinically sound horses were measured on 2 occasions at walk and trot before and after injections with mepivacaine and sodium chloride around the interspinous spaces between T16 and L2. The kinematics were compared between the 2 occasions before injections and before and after each injection. RESULTS: The range of motion (ROM) for dorsoventral flexion-extension (FE) of the back was increased significantly in all measured segments other than T10 at walk, as was lateral bending (LB) at T10, L3 and L5 after injection of mepivacaine. For lateral excursion (LE), total movement increased at all measured segments. At trot the only affected segment was L3, where the injection with mepivacaine decreased the ROM for FE. After injection of sodium chloride the ROM for FE increased at T13 and T17 at walk. Lateral bending and LE were not affected at walk. At trot, LB increased at L3 and L5. CONCLUSIONS AND POTENTIAL RELEVANCE: Diagnostic infiltration of local anaesthetic solution affects the function of the back in clinically sound horses, which must be considered when interpreting the use of this clinical aid in assessing clinical cases of back dysfunction. Kinematics can qualitatively and quantitatively evaluate the effect of local analgesia of the back.