Opioid peptide-expressing leukocytes: identification, recruitment, and simultaneously increasing inhibition of inflammatory pain

Title

Opioid peptide-expressing leukocytes: identification, recruitment, and simultaneously increasing inhibition of inflammatory pain

Creator

Rittner HL; Brack A; Machelska H; Mousa SA; Bauer M; Schafer M; Stein C

Publisher

Anesthesiology

Date

2001

Subject

Male; Pain Measurement; Analgesia; Animals; Rats; beta-Endorphin/blood; Biomarkers of Pain; Pain/physiopathology; Immunohistochemistry; Radioimmunoassay; Biomarkers Reference List; Wistar; Antibodies; Antigens; CD45/isolation & purification; Fluorescent Dyes; Hematopoietic Stem Cells/immunology; Immunomagnetic Separation; Inflammation/chemically induced/metabolism/pathology; Leukocytes/metabolism; Lymphocytes/immunology; Monoclonal/pharmacology; Opioid Peptides/biosynthesis

Description

BACKGROUND: Inflammatory pain can be effectively controlled by an interaction of opioid receptors on peripheral sensory nerve terminals with opioid peptides released from immune cells upon stressful stimulation. To define the source of opioid peptide production, we sought to identify and quantify populations of opioid-containing cells during the course of Freund's complete adjuvant-induced hind paw inflammation in the rat. In parallel, we examined the development of stress-induced local analgesia in the paw. METHODS: At 2, 6, and 96 h after Freund's complete adjuvant inoculation, cells were characterized by flow cytometry using a monoclonal pan-opioid antibody (3E7) and antibodies against cell surface antigens and by immunohistochemistry using a polyclonal antibody to beta-endorphin. After magnetic cell sorting, the beta-endorphin content was quantified by radioimmunoassay. Pain responses before and after cold water swim stress were evaluated by paw pressure thresholds. RESULTS: In early inflammation, 66% of opioid peptide-producing (3E7+) leukocytes were HIS48+ granulocytes. In contrast, at later stages (96 h), the majority of 3E7+ immune cells were ED1+ monocytes or macrophages (73%). During the 4 days after Freund's complete adjuvant inoculation, the number of 3E7+ cells increased 5.6-fold (P < 0.001, Kruskal-Wallis test) and the beta-endorphin content in the paw multiplied 3.9-fold (P < 0.05, Kruskal-Wallis test). In parallel, cold water swim stress-induced analgesia increased by 160% (P < 0.01, analysis of variance). CONCLUSIONS: The degree of endogenous pain inhibition is proportional to the number of opioid peptide-producing cells, and distinct leukocyte lineages contribute to this function at different stages of inflammation. These mechanisms may be important for understanding pain in immunosuppressed states such as cancer, diabetes, or AIDS and for the design of novel therapeutic strategies in inflammatory diseases.
2001

Rights

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).

Type

Journal Article

Citation List Month

Backlog

Pages

500-508

Issue

2

Volume

95

Citation

Rittner HL; Brack A; Machelska H; Mousa SA; Bauer M; Schafer M; Stein C, “Opioid peptide-expressing leukocytes: identification, recruitment, and simultaneously increasing inhibition of inflammatory pain,” Pediatric Palliative Care Library, accessed May 22, 2022, https://pedpalascnetlibrary.omeka.net/items/show/12029.

Social Bookmarking