Opioids produce analgesia by interacting with local opioid receptors i
n peripheral inflamed tissue. This study investigated whether endogeno
us ligands of these receptors are present in synovia and whether such
opioid peptides can inhibit pain by activation of intra-articular opio
id receptors. Samples of synovium from 8 patients undergoing arthrosco
pic knee surgery were examined by immunohistochemistry for the presenc
e of beta-endorphin, met-encephalin, and dynorphin. All tissue samples
showed synovitis. Inflammatory cells stained strongly for beta-endorp
hin and met-encephalin but not for dynorphin. To find out whether bloc
kade of intra-articular opioid receptors affected pain, we randomly as
signed 22 patients undergoing arthroscopic knee surgery to receive nal
oxone (0.04 mg) intra-articularly (n = 10) or intravenously (n = 12);
each patient received a placebo injection into the other site. Postope
rative pain was assessed by visual analogue scale, a numerical rating
scale, the McGill pain questionnaire, and supplementary analgesic cons
umption during the next 24 h. All pain scores were higher in the intra
-articular naloxone group than in the intravenous naloxone group. The
differences were significant (p < 0.05) during the first 4 h. Suppleme
ntary analgesic consumption was significantly higher in the intra-arti
cular group (52.5 14.0! vs 15.6 8.0! mg diclofenac, p < 0.05). Opioi
d peptides are present in inflamed synovial tissue and can inhibit pai
n after knee surgery through an action specific to intra-articular opi
oid receptors, These findings expand the gate control theory of pain a
nd suggest new approaches such as the development of peripherally acti
ng opioid analgesics without central side-effects.