title: Evidence for analgesia mediated by peripheral opioid receptors in inflamed synovial tissue.
abstract: Intra-articular morphine (5 mg in 25 ml) was administered to patients for post-operative analgesia following arthroscopic knee surgery. At various time intervals, 30 min to 4 h post morphine, venous blood samples were taken in order to determine plasma levels of morphine and its primary metabolites, morphine-3-glucuronide and morphine-6-glucuronide. Measurable amounts of morphine and morphine-3-glucuronide were found in the plasma of 7/10 patients whereas morphine-6-glucuronide was detected in only 2/10 patients. The plasma levels of morphine were lower than that regarded sufficient for post-operative analgesia in all but two patients, indicating a possibility of peripheral analgesia. In addition, synovial biopsy samples were assayed for the presence of opioid binding sites. Tissue samples from 11 different patients were analysed and 6/11 exhibited specific binding of [3H]naloxone, indicating the presence of opioid binding sites/receptors. The receptor type (i.e. mu-, delta- or k-) is at present unknown. Taken together, these data provide evidence that locally administered opiates can act on specific opioid receptors in the synovium to mediate analgesia.
authors.affiliation: Pain Research Institute, Liverpool, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Lawrence
authors.forename: G P
authors.initials: GP
authors.lastname: Joshi
authors.forename: A
authors.initials: A
authors.lastname: Michalkiewicz
authors.forename: W P
authors.initials: WP
authors.lastname: Blunnie
authors.forename: D C
authors.initials: DC
authors.lastname: Moriarty
mesh_terms: D000328:Adult; D000698:Analgesia; D001182:Arthroscopy / Q000009:adverse effects; D005260:Female; D006801:Humans; D007717:Knee / Q000601:surgery; D008297:Male; D009020:Morphine / Q000097:blood / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000097:blood; D010149:Postoperative Pain / Q000188:drug therapy*; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D013585:Synovitis / Q000097:blood / Q000378:metabolism*
chemical_list: D009022:Morphine Derivatives; D011957:Receptors, Opioid; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide