Gene expression and localization of opioid peptides in immune cells of inflamed tissue: functional role in antinociception
Male; Pain Measurement; Analysis of Variance; Animals; Nucleic Acid Hybridization; Rats; Non-U.S. Gov't; Research Support; Biomarkers of Pain; RNA; Biomarkers Reference List; Inbred Strains; beta-Endorphin/genetics/metabolism; Calcitonin Gene-Related Peptide/analysis/metabolism; Endorphins/analysis/genetics/metabolism; Freund's Adjuvant; Gene Expression/radiation effects; Hindlimb; Inflammation/immunology/physiopathology; Messenger/genetics/metabolism; Nerve Fibers/physiology/ultrastructure; Oligonucleotide Probes; Pain/immunology/physiopathology; T-Lymphocytes/immunology/pathology; Whole-Body Irradiation
Our previous studies indicate that endogenous opioids (primarily beta-endorphin) released during stressful stimuli can interact with peripheral opioid receptors to inhibit nociception in inflamed tissue of rats. This study sought to localize opioid precursor mRNAs and opioid peptides deriving therefrom in inflamed tissue, identify opioid containing cells and demonstrate their functional significance in the inhibition of nociception. In rats with Freund's adjuvant-induced unilateral hindpaw inflammation we show that: (i) pro-opiomelanocortin and proenkephalin-mRNAs (but not prodynorphin mRNA) are abundant in cells of inflamed, but absent in non-inflamed tissue; (ii) numerous cells infiltrating the inflamed subcutaneous tissue are stained intensely with beta-endorphin and [Met]enkephalin (but only few scattered cells with dynorphin) antibodies; (iii) beta-endorphin is present in T- and B-lymphocytes, monocytes and macrophages; and (iv) whole-body irradiation suppresses stress-induced antinociception in the inflamed paw. Taken together, these data suggest that endogenous opioid peptides are synthesized and processed within various types of immune cells at the site of inflammation. Immunosuppression abolishes the intrinsic antinociception in inflammatory tissue confirming the functional significance of these cells.
1992
Przewlocki R; Hassan AH; Lason W; Epplen C; Herz A; Stein C
Neuroscience
1992
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/10.1016/0306-4522(92)90509-z" target="_blank" rel="noreferrer">10.1016/0306-4522(92)90509-z</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>