Lymphocytes upregulate signal sequence-encoding proopiomelanocortin mRNA and beta-endorphin during painful inflammation in vivo
Male; Time Factors; Animals; Rats; Biomarkers of Pain; RNA; beta-Endorphin/metabolism; Freund's Adjuvant; Wistar; Lymphocytes/metabolism; Flow Cytometry/methods; Gene Expression Regulation/drug effects/physiology; Inflammation/chemically induced/complications/pathology; Messenger/metabolism; Pain/etiology/pathology; Pro-Opiomelanocortin/genetics/metabolism; Protein Sorting Signals; Reverse Transcriptase Polymerase Chain Reaction/methods
Proopiomelanocortin (POMC)-derived beta-endorphin1-31 (END) released from immune cells inhibits inflammatory pain. We examined the expression of END and POMC mRNA encoding the signal sequence required for entry of the nascent polypeptide into the regulated secretory pathway in lymphocytes of rats with inflamed hindpaws. Within 12 h of inflammation, END increased in popliteal lymph nodes and at 96 h the intraplantar neutralization of END exacerbated pain. Lymphocytes expressed POMC, END, and full-length POMC mRNA. Semi-nested PCR revealed 8-fold increased exon 2-3 spanning POMC mRNA. Thus, painful inflammation enhances signal sequence-encoding lymphocytic POMC mRNA needed for regulated secretion of functionally active END.
2007
Sitte N; Busch M; Mousa SA; Labuz D; Rittner H; Gore C; Krause H; Stein C; Schafer M
Journal Of Neuroimmunology
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/10.1016/j.jneuroim.2006.11.033" target="_blank" rel="noreferrer">10.1016/j.jneuroim.2006.11.033</a>
Different mechanisms of intrinsic pain inhibition in early and late inflammation
Male; Time Factors; Pain Threshold; Animals; Rats; Biomarkers of Pain; Injections; Subcutaneous; Enkephalin; Hindlimb; Wistar; Corticotropin-Releasing Hormone/administration & dosage; Dynorphins/antagonists & inhibitors/biosynthesis/physiology; Edema/immunology/metabolism/physiopathology; Endorphins/antagonists & inhibitors/biosynthesis/physiology; Freund's Adjuvant/administration & dosage; Inflammation/immunology/metabolism/physiopathology; Leukocytes/drug effects/metabolism/physiology; Methionine/antagonists & inhibitors/biosynthesis/physiology; Naloxone/administration & dosage; Pain/immunology/pathology/prevention & control; Stress/immunology/metabolism/physiopathology
Neuroimmune interactions control pain through activation of opioid receptors on sensory nerves by immune-derived opioid peptides. Here we evaluate mechanisms of intrinsic pain inhibition at different stages of Freund's adjuvant-induced inflammation of the rat paw. We use immunohistochemistry and paw pressure testing. Our data show that in early (6 h) inflammation leukocyte-derived beta-endorphin, met-enkephalin and dynorphin A activate peripheral mu-, delta- and kappa-receptors to inhibit nociception. In addition, central opioid mechanisms seem to contribute significantly to this effect. At later stages (4 days), antinociception is exclusively produced by leukocyte-derived beta-endorphin acting at peripheral mu and delta receptors. Corticotropin-releasing hormone (CRH) is an endogenous trigger of these effects at both stages. These findings indicate that peripheral opioid mechanisms of pain inhibition gain functional relevance with the chronicity of inflammation.
2003
Machelska H; Schopohl JK; Mousa SA; Labuz D; Schafer M; Stein C
Journal Of Neuroimmunology
2003
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/s0165-5728(03)00213-3" target="_blank" rel="noreferrer">10.1016/s0165-5728(03)00213-3</a>
Tissue monocytes/macrophages in inflammation: hyperalgesia versus opioid-mediated peripheral antinociception
Male; Analgesics; Animals; Rats; Biomarkers of Pain; Injections; Pain Measurement/drug effects; Freund's Adjuvant; Wistar; Flow Cytometry; Foot/pathology; Opioid/administration & dosage/pharmacology; Clodronic Acid/pharmacokinetics/pharmacology; Fentanyl/administration & dosage/pharmacology; Heat; Hyperalgesia/chemically induced/pathology/psychology; Inflammation/chemically induced/pathology; Liposomes; Macrophages/pathology; Monocytes/pathology; Non-Narcotic/pharmacokinetics/pharmacology; Pressure
BACKGROUND: Opioid-containing leukocytes migrate to peripheral sites of inflammation. On exposure to stress, opioid peptides are released, bind to opioid receptors on peripheral sensory neurons, and induce endogenous antinociception. In later stages of Freund's complete adjuvant-induced local inflammation, monocytes/macrophages are a major opioid-containing leukocyte subpopulation, but these cells also produce proalgesic cytokines. In this study, the role of tissue monocytes/macrophages in hyperalgesia and in peripheral opioid-mediated antinociception was investigated. METHODS: After intraplantar injection of Freund's adjuvant, leukocyte subpopulations and opioid-containing leukocytes were analyzed by flow cytometry in the inflamed paw in the presence or absence of monocyte/macrophage depletion by intraplantar injection of clodronate-containing liposomes (phosphate-buffered saline and empty liposomes served as controls). Paw volume was measured with a plethysmometer. Hyperalgesia was determined by measuring heat-induced paw withdrawal latency and paw pressure threshold. Paw pressure threshold was also measured after swim stress and injection of fentanyl. RESULTS: At 48 and 96 h of inflammation, it was found that (1). monocytes/macrophages were the largest leukocyte subpopulation (> 55% of all leukocytes) and the predominant producers of opioid peptides (71-77% of all opioid-containing leukocytes in the paw), (2). clodronate-containing liposomes depleted monocytes/macrophages by 30-35% (P 0.05), and (4) opioid-containing leukocytes and swim stress but not fentanyl-induced antinociception were significantly decreased by clodronate-containing liposomes (P 0.05, all by t test; opioid-containing cells and swim stress-induced increase of paw pressure threshold were reduced by 35-42% and 20%, respectively). CONCLUSION: Partial depletion of tissue monocytes/macrophages impairs peripheral endogenous opioid-mediated antinociception without affecting hyperalgesia.
2004
Brack A; Labuz D; Schiltz A; Rittner HL; Machelska H; Schafer M; Reszka R; Stein C
Anesthesiology
2004
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/10.1097/00000542-200407000-00031" target="_blank" rel="noreferrer">10.1097/00000542-200407000-00031</a>
JAK-STAT1/3-induced expression of signal sequence-encoding proopiomelanocortin mRNA in lymphocytes reduces inflammatory pain in rats
Biomarkers of Pain
Busch-Dienstfertig M; Labuz D; Wolfram T; Vogel NN; Stein C
Molecular Pain
2012
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/10.1186/1744-8069-8-83" target="_blank" rel="noreferrer">10.1186/1744-8069-8-83</a>