Modulation of Peripheral Endogenous Opioid Analgesia by Central Afferent Blockade

2003 ◽  
Vol 98 (1) ◽  
pp. 195-202 ◽  
Author(s):  
Thomas K. Schmitt ◽  
Shaaban A. Mousa ◽  
Alexander Brack ◽  
Diego K. Schmidt ◽  
Heike L. Rittner ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Cells ◽  
Cold Water ◽  
Intrathecal Morphine ◽  
Opioid Analgesia ◽  
Endogenous Opioid ◽  
Freund’S Complete Adjuvant ◽  
Freund's Complete Adjuvant ◽  
Pressure Threshold ◽  
Endogenous Analgesia

Background Peripheral tissue injury causes a migration of opioid peptide-containing immune cells to the inflamed site. The subsequent release and action of these peptides on opioid receptors localized on peripheral sensory nerve terminals causes endogenous analgesia. The spinal application of opioid drugs blocks the transmission of nociceptive information from peripheral injury. This study investigates the influence of exogenous spinal opioid analgesia on peripheral endogenous opioid analgesia. Methods Six and forty-eight hours after initiation of continuous intrathecal morphine infusion and administration of Freund's complete adjuvant into the hind paw of rats, antinociceptive and antiinflammatory effects were measured by paw pressure threshold, paw volume, and paw temperature, respectively. Inflammation and quantity of opioid-containing cells were evaluated by immunocytochemistry and flow cytometry. Cold water swim stress-induced endogenous analgesia was examined 24 h after discontinuation of intrathecal morphine administration. Results Intrathecal morphine (10 micro g/h) resulted in a significant and stable increase of paw pressure threshold ( P< 0.05) without changing inflammation, as evaluated by paw volume, paw temperature, and flow cytometry ( P> 0.05). At 48 but not at 6 h after Freund's complete adjuvant, the number of beta-endorphin-containing cells and cold water swim-induced antinociception were significantly reduced in intrathecal morphine-treated rats compared with those treated with intrathecal vehicle ( P< 0.05). Conclusions These findings suggest an interplay of central and peripheral mechanisms of pain control. An effective central inhibition of pain apparently signals a reduced need for recruitment of opioid-containing immune cells to injured sites.

Opioid Peptide–expressing Leukocytes

2001 ◽  
Vol 95 (2) ◽  
pp. 500-508 ◽  
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.

Endogenous opioids mediate stress-induced analgesia

2018 ◽  
Author(s):  
Claudia Sommer
Keyword(s):  
Opioid Receptors ◽  
Immune Cells ◽  
Endogenous Opioids ◽  
Sensory Nerves ◽  
Opioid Analgesia ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
First Time ◽  
Endogenous Analgesia

This chapter reviews the landmark paper published in 1990 by Stein et al. and entitled ‘Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation’. Opioids, besides acting centrally as analgesics, may act peripherally upon opioid receptors located on axons and on immune cells. In the publication by Stein et al., it was shown for the first time that endogenous opioid peptides released from immune cells mediate stress-induced analgesia, potentially through opioid receptors on peripheral nerve endings. This finding has led to numerous follow-up studies on endogenous analgesia, including work showing that cannabinoid analgesia is mediated via the peripheral release of opioids, and to the concept of topical opioid analgesia, which may be a good way of using the potent analgesia that opioids can convey, without their CNS-associated side effects.

scholarly journals Sigma-1 receptors control immune-driven peripheral opioid analgesia during inflammation in mice

2017 ◽  
Vol 114 (31) ◽  
pp. 8396-8401 ◽  
Author(s):  
Miguel A. Tejada ◽  
Angeles Montilla-García ◽  
Shane J. Cronin ◽  
Domagoj Cikes ◽  
Cristina Sánchez-Fernández ◽  
...  
Keyword(s):  
Immune Cells ◽  
Thermal Hyperalgesia ◽  
Opioid Analgesia ◽  
Endogenous Opioid ◽  
Drug Induced ◽  
Immune Infiltrate ◽  
Pathophysiological Role ◽  
Sigma 1 ◽  
Peripheral Opioid Analgesia

Sigma-1 antagonism potentiates the antinociceptive effects of opioid drugs, so sigma-1 receptors constitute a biological brake to opioid drug-induced analgesia. The pathophysiological role of this process is unknown. We aimed to investigate whether sigma-1 antagonism reduces inflammatory pain through the disinhibition of the endogenous opioidergic system in mice. The selective sigma-1 antagonists BD-1063 and S1RA abolished mechanical and thermal hyperalgesia in mice with carrageenan-induced acute (3 h) inflammation. Sigma-1–mediated antihyperalgesia was reversed by the opioid antagonists naloxone and naloxone methiodide (a peripherally restricted naloxone analog) and by local administration at the inflamed site of monoclonal antibody 3-E7, which recognizes the pan-opioid sequence Tyr–Gly–Gly–Phe at the N terminus of most endogenous opioid peptides (EOPs). Neutrophils expressed pro-opiomelanocortin, the precursor of β-endorphin (a known EOP), and constituted the majority of the acute immune infiltrate. β-endorphin levels increased in the inflamed paw, and this increase and the antihyperalgesic effects of sigma-1 antagonism were abolished by reducing the neutrophil load with in vivo administration of an anti-Ly6G antibody. The opioid-dependent sigma-1 antihyperalgesic effects were preserved 5 d after carrageenan administration, where macrophages/monocytes were found to express pro-opiomelanocortin and to now constitute the majority of the immune infiltrate. These results suggest that immune cells harboring EOPs are needed for the antihyperalgesic effects of sigma-1 antagonism during inflammation. In conclusion, sigma-1 receptors curtail immune-driven peripheral opioid analgesia, and sigma-1 antagonism produces local opioid analgesia by enhancing the action of EOPs of immune origin, maximizing the analgesic potential of immune cells that naturally accumulate in painful inflamed areas.

Experimental Amyloidosis Induced by Immune Complex

1971 ◽  
Vol 29 ◽  
pp. 582-583
Author(s):  
A. Kawaoi
Keyword(s):  
Immune Complex ◽  
Systemic Amyloidosis ◽  
Human Diseases ◽  
Experimental Amyloidosis ◽  
Freund’S Complete Adjuvant ◽  
Freund's Complete Adjuvant ◽  
Immunological Approach ◽  
Experimentally Induced

Numbers of immunological approach have been made to the amyloidosis through the variety of predisposing human diseases and the experimentally induced animals by the greater number of agents. The results suggest an important role of impaired immunity involving both humoral and cell-mediated aspects.Recently the author has succeeded in producing amyloidosis in the rabbits and mice by the injections of immune complex of heat denatured DNA.The aim of this report is to demonstrate the details of the ultrastructure of the amyloidosis induced by heterologous insoluble immune complex. Eleven of twelve mice, dd strain, subcutaneously injected twice a week with Freund's complete adjuvant and four of seven animals intraperitonially injected developed systemic amyloidosis two months later from the initial injections. The spleens were electron microscopically observed.

scholarly journals POS0369 ELEVATED EXPRESSION OF TIM-3 ON NEUTROPHILS CORRELATES WITH DISEASE ACTIVITY AND SEVERITY OF ANKYLOSING SPONDYLITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 414.2-415
Author(s):  
X. Huang ◽  
T. W. Li ◽  
J. Chen ◽  
Z. Huang ◽  
S. Chen ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Immune Cells ◽  
Clinical Manifestations ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Bacterial Killing ◽  
Markers Of Inflammation ◽  
Significant Difference

Background:Ankylosing spondylitis (AS) is a type of common, chronic inflammatory disease that compromises the axial skeleton and sacroiliac joints, causing inflammatory low back pain and progressive spinal stiffness, over time some patients develop spinal immobility and ankylosis which can lead to a decrease in quality of life. The last few decades, evidence has clearly indicated that neutrophil also plays key roles in the progression of AS. However, the immunomodulatory roles and mechanisms of neutrophils in AS are poorly understood. T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) has been reported as an important regulatory molecule, expressed and regulated on different innate immune cells, plays a pivotal role in several autoimmunity diseases. Recent study indicates that Tim3 is also expressed on neutrophils. However, the frequency and roles of Tim3-expressing neutrophils in AS was not clear.Objectives:In this study, we investigated the expression of Tim3 on neutrophils in AS patients and explored the correlation between the level of Tim3-expressing neutrophils and the disease activity and severity of AS.Methods:Patients with AS were recruited from Guangdong Second Provincial General Hospital (n=62). Age/sex-matched volunteers as Healthy controls (HC) (n=39). The medical history, clinical manifestations, physical examination, laboratory measurements were recorded. The expression of costimulatory molecules including programmed death 1 (PD-1), Tim-3 on neutrophils were determined by flow cytometry. The mRNA expression of PD-1 and Tim-3 was determined by real-time PCR. The levels of Tim3-expressing neutrophils in AS patients were further analyzed for their correlation with the markers of inflammation such as ESR,CRP,WBC and neutrophil count(NE), as well as disease activity and severity of AS. The expression of Tim3 on neutrophils was monitored during the course of treatment (4 weeks).Results:The expression of Tim3 on neutrophils in patients with AS was increased compared to the HC (Figure 1A). However, significant difference was observed in the frequency of PD-1-expressing neutrophils between AS patients and HC (Figure 1B). The expression analysis of Tim-3 mRNA, but not PD-1, confirmed the results obtained from flow cytometry (Figure 1C). The level of Tim3-expressing neutrophils in patients with AS showed an positive correlation with ESR, CRP and ASAS-endorsed disease activity score (ASDAS) (Figure 1D). Moreover, the frequency of Tim3-expressing neutrophils in active patients(ASDAS≥1.3) was increased as compare with the inactive patients (ASDAS<1.3) (Figure 1E). As shown in Figure 1F, the frequency of Tim3-expressing neutrophils decreased after the treatment.Conclusion:Increased Tim-3 expression on neutrophils may be a novel indicator to assess disease activity and severity in AS, which may serves as a negative feedback mechanism preventing potential tissue damage caused by excessive inflammatory responses in AS patients.References:[1]Han, G., Chen, G., Shen, B. & Li, Y., Tim-3: an activation marker and activation limiter of innate immune cells. FRONT IMMUNOL 4 449 (2013).[2]Vega-Carrascal, I. et al., Galectin-9 signaling through TIM-3 is involved in neutrophil-mediated Gram-negative bacterial killing: an effect abrogated within the cystic fibrosis lung. J IMMUNOL 192 2418 (2014).Figure 1.(A,B)The expression of Tim3 and PD-1 on neutrophils in AS and HC were determined by flow cytometry.(C) The expression of Tim3 and PD-1 on neutrophils in AS and HC were determined by RT-PCR.(D)The correction between Tim3-expressing neutrophils and ESR,CRP,ASDAS.(E) The expression of Tim3 on neutrophils in active and inactive patients.(F) Influence of treatment on the frequency of Tim3-expressing neutrophils.Disclosure of Interests:None declared

scholarly journals Mouse IgG3 binding to macrophage-like cells is prevented by deglycosylation of the antibody or by Accutase treatment of the cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alicja Karabasz ◽  
Monika Bzowska ◽  
Joanna Bereta ◽  
Maria Czarnek ◽  
Maja Sochalska ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Complex Network ◽  
Immune Cells ◽  
Specific Receptor ◽  
Fcγ Receptors ◽  
Specific Receptors ◽  
First Time

AbstractThe binding of mouse IgG3 to Fcγ receptors (FcγR) and the existence of a mouse IgG3-specific receptor have been discussed for 40 years. Recently, integrin beta-1 (ITGB1) was proposed to be a part of an IgG3 receptor involved in the phagocytosis of IgG3-coated pathogens. We investigated the interaction of mouse IgG3 with macrophage-like J774A.1 and P388D1 cells. The existence of an IgG3-specific receptor was verified using flow cytometry and a rosetting assay, in which erythrocytes clustered around the macrophage-like cells coated with an erythrocyte-specific IgG3. Our findings confirmed that receptors binding antigen-free IgG3 are present on J774A.1 and P388D1 cells. We demonstrated for the first time that the removal of N-glycans from IgG3 completely abolished its binding to the cells. Moreover, we discovered that the cells treated with Accutase did not bind IgG3, indicating that IgG3-specific receptors are substrates of this enzyme. The results of antibody-mediated blocking of putative IgG3 receptors suggested that apart from previously proposed ITGB1, FcγRII, FcγRIII, also additional, still unknown, receptor is involved in IgG3 binding. These findings indicate that there is a complex network of glycan-dependent interactions between mouse IgG3 and the surface of effector immune cells.

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