Neuronal mechanisms of the recruitment of opioid peptide expressing immune cells

Subcellular Pathways of β-Endorphin Synthesis, Processing, and Release from Immunocytes in Inflammatory Pain

Endocrinology ◽

10.1210/en.2003-1287 ◽

2004 ◽

Vol 145 (3) ◽

pp. 1331-1341 ◽

Cited By ~ 107

Author(s):

Shaaban A. Mousa ◽

Mehdi Shakibaei ◽

Nicolle Sitte ◽

Michael Schäfer ◽

Christoph Stein

Keyword(s):

Opioid Receptors ◽

Immune Cells ◽

Inflammatory Pain ◽

Secretory Granules ◽

Inflammatory Cells ◽

Opioid Peptide ◽

Active Peptides ◽

Carboxypeptidase E ◽

Peripheral Opioid Receptors

Abstract The opioid peptide β-endorphin (END) as well as mRNA for its precursor proopiomelanocortin (POMC) are found not only in the pituitary gland, but also within various types of immune cells infiltrating inflamed sc tissue. During stressful stimuli END is released and interacts with peripheral opioid receptors to inhibit pain. However, the subcellular pathways of POMC processing and END release have not yet been delineated in inflammatory cells. The aim of the present study was to examine the presence of POMC, carboxypeptidase E, the prohormone convertases 1 (PC1), and 2 (PC2), PC2-binding protein 7B2, and the release of END from inflammatory cells in rats. Using immunohistochemistry we detected END and POMC alone or colocalized with PC1, PC2, carboxypeptidase E, and 7B2 in macrophages/monocytes, granulocytes, and lymphocytes of the blood and within inflamed sc paw tissue. Immunoelectron microscopy revealed that END is localized within secretory granules packed in membranous structures in macrophages, monocytes, granulocytes, and lymphocytes. Finally, END is released by noradrenaline from immune cells in vitro. Taken together, our results indicate that immune cells express the entire machinery required for POMC processing into functionally active peptides such as END and are able to release these peptides from secretory granules.

Download Full-text

Opioid Peptide–expressing Leukocytes

Anesthesiology ◽

10.1097/00000542-200108000-00036 ◽

2001 ◽

Vol 95 (2) ◽

pp. 500-508 ◽

Cited By ~ 139

Author(s):

Heike L. Rittner ◽

Alexander Brack ◽

Halina Machelska ◽

Shaaban A. Mousa ◽

Monika Bauer ◽

...

Keyword(s):

Immune Cells ◽

Cold Water ◽

Inflammatory Diseases ◽

Sensory Nerve ◽

Opioid Peptide ◽

Cell Surface Antigens ◽

Swim Stress ◽

Freund’S Complete Adjuvant ◽

Beta Endorphin ◽

Freund's Complete Adjuvant

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.

Download Full-text

Alleviation of pain and depression by specific neural transplants: Fine structural correlates

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100129966 ◽

1992 ◽

Vol 50 (2) ◽

pp. 1066-1067

Author(s):

George D. Pappas ◽

Jacqueline Sagen

Keyword(s):

Opioid Peptides ◽

Chromaffin Cells ◽

Pain Sensitivity ◽

Opioid Peptide ◽

Local Source ◽

Pain Models ◽

Neural Transplants ◽

Adrenergic Antagonists ◽

Csf Levels ◽

Donor Source

We have been interested in the use of neural transplants mainly as a local source of neuroactive substances, rather than as a replacement for damaged neural circuities. In particular, we have been exploring the possibilities of reducing pain by transplants of opioid peptide producing cells, and reducing depression by transplants of monoamine-producing cells. For the past several years, work in our laboratory has demonstrated in both acute and chronic pain models that transplantation of adrenal medullary tissue or isolated chromaffin cells into CNS pain modulatory regions can reduce pain sensitivity in rodents. Chromaffin cells were chosen as donor source since they produce high levels of both opioid peptides and catecholamines, substances which independently, and probably synergistically, reduce pain sensitivity when injected locally into the spinal cord. The analgesia produced by these transplants most likely results from the release of both opioid peptides and catecholamines, since it can be blocked or attenuated by opiate or adrenergic antagonists, respectively. Furthermore, CSF levels of met-enkephalin and catecholamines are increased by the transplants.

Download Full-text