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

Abstract

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.