Research PaperEffects of intraarticular ropivacaine and morphine on lipopolysaccharide‐induced synovitis in horses
Introduction
Joint injuries are common in horses and, in one survey, 33% of lameness originated from articular injuries (Leme et al. 1999). Pathologic conditions that involve the joints of horses cause a decrease in their athletic performance (Todhunter & Lust 1990). Primary synovitis is a lesion that usually develops in the carpal and metacarpo/metatarsophalangeal joint of young horses during the early stages of training (McIlwraith 1987). Synovitis is characterized by joint effusion and decreased range of motion. Pain is generated when thermal, chemical and mechanical stimuli in the joint activate peripheral afferent fibers (Hall et al. 2001). Additionally, the release of proinflammatory mediators (bradykinins, prostaglandins and leukotrienes) decreases the potential for activation of peripheral afferent receptors (Todhunter & Lust 1990).
Pre‐emptive, peri‐operative, and post‐operative/post‐injury analgesia for synovitis can be provided in a number of ways. Combinations of different analgesic methods, described as multimodal analgesia, have proven to be highly effective in other species and should be appropriate for horses (Aguiar 2005). Combinations of analgesics that act through different mechanisms produce a synergistic or at least additive effect (Aguiar 2005; Taylor 2005). Evidence shows that opioids, such as morphine, can produce an analgesic effect through peripheral receptors (Stein 1996; Sheehy et al. 2001; Benson 2002) and this analgesic effect is enhanced in the presence of inflammation (Keates et al. 1999). Studies in humans (Stein et al. 1991) and in dogs (Sammarco et al. 1996; Keates et al.1999) indicated that small doses of intraarticular (IA) morphine can promote effective analgesia after arthroscopic surgery.
Local anesthetics are often used in equine practice for both diagnosis and treatment of musculoskeletal injuries of the distal limbs (Monteiro 2005). Local anesthetics act by producing conduction blockade in sensory neurons and retarding the influx of Na+ ions. They have variable potency, stability, toxicity and capability of penetrating different tissues. Ropivacaine is a long‐lasting amino‐amide local anesthetic (McClure 1996) that shows similar physical properties to bupivacaine, except that it is a pure S‐(−) enantiomer. Ropivacaine promotes vasoconstriction whereas lidocaine, mepivacaine and bupivacaine promote vasodilation (Hall et al. 2001). Rautoma et al. (2000) claim that ropivacaine has dynamic and kinetic functions that are similar to bupivacaine but with less neuronal and cardiac toxicity, furthermore, its decreased lipid solubility, mainly on myelinated motor fibers (alpha), shows that ropivacaine contributes to a faster return of motor function (Williams 1996). To date, there is little or no information available concerning the disposition and pharmacokinetics of ropivacaine and its effects on joint analgesia in horses. The present study evaluated the analgesia provided by ropivacaine and morphine in horses with lipopolysaccharide‐induced synovitis.
Section snippets
Materials and methods
Horses used in this experiment were managed according to the rules and regulations of the Institutional Animal Care Use Committee at the University (protocol 1.28/05). Twelve healthy mixed breed horses aged 8–15 years and weighing 316 ± 33 kg (weight range from 280 to 380 kg) were randomly assigned to four equal treatment groups: Saline/control (SAL), ropivacaine (ROPI) (1% ropivacaine chloride, Naropin; Astra Zeneca, MA, USA), morphine (MOR) (1% morphine sulphate; Dimorf, Cristália Ltda,
Results
There were no significant differences between the groups in age, sex, body weight or height. None of our horses received any systemic or parenteral analgesic medication during the experiment. Appetite and water intake were unaffected by IA LPS injection or treatments when hay and water were offered during the day. Rectal temperature remained normal except for a statistically, but not clinically significant, transient increase (38.2 °C) at T3.5 in the ROPI group. There was a mild increase in
Discussion
Our results support the hypothesis that morphine and ropivacaine have profound analgesic effects on LPS‐induced synovitis in horses. Our findings indicate that IA ropivacaine produced analgesia with an onset of action of 30 minutes. However, its clinical effects (NRS and SDS score < 1) lasted sometime between T2.5and T3.5 hours in inflamed tissue. On the other hand, morphine, despite having a slower onset of action (30–60 minutes) than ropivacaine, had prolonged effects, lasting 24 hours.
Conclusions
Intraarticular injection of 0.5 ng LPS created a transitory inflammation with an increase of TNC in the synovial fluid, as well as an increase in total protein associated with physical and biochemical alterations. Ropivacaine had a fast onset and a short analgesic action while morphine lasted longer when administered in inflamed joints. Therefore the best way to achieve fast and long analgesia is a combination of ropivacaine and morphine. The easy application and minimal side effects make it a
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