Opioids
Humans; Analgesics; Animals; Molecular Sequence Data; Chronic disease; Biomarkers of Pain; Drug Tolerance; Receptors; Amino Acid Sequence; Ligands; Opioid/adverse effects/pharmacology/therapeutic use; Opioid/drug effects
Opioids are the most effective and widely used drugs in the treatment of severe pain. They act through G protein-coupled receptors. Four families of endogenous ligands (opioid peptides) are known. The standard exogenous opioid analgesic is morphine. Opioid agonists can activate central and peripheral opioid receptors. Three classes of opioid receptors (mu, delta, kappa) have been identified. Multiple pathways ofopioid receptor signaling (e.g., G(i/o) coupling, cAMP inhibition, Ca++ channel inhibition) have been described. The differential regulation of effectors, preclinical pharmacology, clinical applications, and side effects will be reviewed in this chapter.
2007
Zollner C; Stein C
Handbook Of Experimental Pharmacology
2007
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1007/978-3-540-33823-9_2" target="_blank" rel="noreferrer">10.1007/978-3-540-33823-9_2</a>
Local analgesic effect of endogenous opioid peptides
Humans; Pain; Adult; Aged; Middle Aged; Double-Blind Method; Biomarkers of Pain; Injections; Intravenous; Receptors; Opioid/drug effects; Immunohistochemistry; Enkephalin; Arthroscopy; beta-Endorphin/analysis/physiology; Dynorphins/analysis/physiology; Endorphins/analysis/physiology; Intra-Articular; Knee Joint/surgery; Methionine/analysis/physiology; Naloxone/administration & dosage/pharmacology; Postoperative/etiology; Synovial Membrane/chemistry; Synovitis/metabolism
Opioids produce analgesia by interacting with local opioid receptors in peripheral inflamed tissue. This study investigated whether endogenous ligands of these receptors are present in synovia and whether such opioid peptides can inhibit pain by activation of intra-articular opioid receptors. Samples of synovium from 8 patients undergoing arthroscopic knee surgery were examined by immunohistochemistry for the presence of beta-endorphin, met-enkephalin, and dynorphin. All tissue samples showed synovitis. Inflammatory cells stained strongly for beta-endorphin and met-enkephalin but not for dynorphin. To find out whether blockade of intra-articular opioid receptors affected pain, we randomly assigned 22 patients undergoing arthroscopic knee surgery to receive naloxone (0.04 mg) intra-articularly (n = 10) or intravenously (n = 12); each patient received a placebo injection into the other site. Postoperative pain was assessed by visual analogue scale, a numerical rating scale, the McGill pain questionnaire, and supplementary analgesic consumption 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. Supplementary analgesic consumption was significantly higher in the intra-articular group (52.5 [14.0] vs 15.6 [8.0] mg diclofenac, p < 0.05). Opioid peptides are present in inflamed synovial tissue and can inhibit pain after knee surgery through an action specific to intra-articular opioid receptors. These findings expand the gate control theory of pain and suggest new approaches such as the development of peripherally acting opioid analgesics without central side-effects.
1993
Stein C; Hassan AH; Lehrberger K; Giefing J; Yassouridis A
Lancet
1993
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1016/0140-6736(93)91471-w" target="_blank" rel="noreferrer">10.1016/0140-6736(93)91471-w</a>
The control of pain in peripheral tissue by opioids
Humans; Animals; Biomarkers of Pain; Pain/drug therapy; Receptors; Opioid/drug effects; Narcotics/therapeutic use; Neurons; Afferent/drug effects; Peripheral Nervous System Diseases/drug therapy/physiopathology
1995
Stein C
The New England Journal Of Medicine
1995
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1056/nejm199506223322506" target="_blank" rel="noreferrer">10.1056/nejm199506223322506</a>