Intraarticular and periarticular opioid binding in inflamed tissue in experimental canine arthritis

H L Keates, T Cramond, M T Smith
Anesthesia and Analgesia 1999, 89 (2): 409-15

UNLABELLED: Small-dose (1 mg) intraarticular morphine has been used successfully in many studies to provide long-lasting analgesia after arthroscopic knee surgery. We used radioligand binding to determine whether these effects could be mediated by opioid binding sites in the joint, particularly after the induction of inflammation. Inflammation was induced by the injection of oleyl alcohol (20 microL) in sterile peanut oil (0.25 mL) into the left radiocarpal joint of 27 dogs, and the dogs were euthanized at 12 h. The articular and periarticular tissues from both treated and control joints were collected, and membranes were prepared for equilibrium binding assays. The density of specific opioid binding was markedly enhanced (P < 0.05) in homogenates prepared from the treated relative to those from the control joint. The binding affinities (KD values) for morphine and naloxone (mean +/- SEM) were approximately one one-hundredth (79 +/- 17 nM and 124 +/- 5.5 nM, respectively) that of the corresponding published affinities in brain tissue. However, the binding site densities were approximately one hundred times larger (Bmax = 1032 +/- 265 and 543 +/- 51 fmol/mg of protein) than the respective published values in brain tissue. These findings imply that the opioid binding sites, found in the inflamed articular and periarticular tissues in this study, are similar to those of putative mu 3-opioid binding sites that appear to be present on cultured thymocytes and in the airways of rats and humans.

IMPLICATIONS: The high density of opioid binding sites found in inflamed canine joint tissue supports the clinical use of intraarticular opioids in the treatment of postoperative and chronic inflammatory joint pain.

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