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Involvement of CD4 + and CD8 + T-lymphocytes in the modulation of nociceptive processing evoked by CCL4 in mice.
- Source :
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Life sciences [Life Sci] 2022 Feb 15; Vol. 291, pp. 120302. Date of Electronic Publication: 2022 Jan 06. - Publication Year :
- 2022
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Abstract
- Aims: To explore the mechanisms involved in the transformation of analgesia produced by low doses of CCL4 (pg/kg) to hyperalgesia when higher doses (ng/kg) are administered to mice.<br />Main Methods: The unilateral hot plate test was used to assess thermal nociception. CD3 <superscript>+</superscript> , CD4 <superscript>+</superscript> or CD8 <superscript>+</superscript> blood cells were depleted with selective antibodies. Expression of CCR5 and IL-16 in lymphocytes was studied by flow cytometry and IL-16 blood levels were measured by ELISA. IL-16 and CD8 were detected by immunofluorescence.<br />Key Findings: IL-16 and CCR5 expression were demonstrated in CD4 <superscript>+</superscript> and CD8 <superscript>+</superscript> T-lymphocytes by flow cytometry. Furthermore, CCL4-induced hyperalgesia was abolished by reducing circulating T-lymphocyte levels or by selectively depleting CD4 <superscript>+</superscript> lymphocytes. In contrast, when the anti-CD4 antibody was acutely administered, CCL4 induced analgesia instead of hyperalgesia. A similar response was obtained when administering A-770041, that prevents CD4-mediated CCR5 desensitization by inhibiting p56 <superscript>lck</superscript> kinase. As occurred with the analgesic effect evoked by low doses of CCL4, analgesia evoked by combining CCL4 and A-770041 was reverted by naloxone, naltrindole or an anti-met-enk antibody. Interestingly, flow cytometry assays showed that the number of CD8 <superscript>+</superscript> , but not CD4 <superscript>+</superscript> , T-cells expressing IL-16 is reduced after the acute administration of CCL4, a result compatible with the description that CD8 <superscript>+</superscript> -lymphocytes can rapidly release preformed IL-16. Accordingly, the rise in IL-16 blood concentration evoked by CCL4 was prevented after CD8 <superscript>+</superscript> lymphocyte depletion.<br />Significance: CCL4-evoked hyperalgesia is related to the desensitization of CCR5 in CD4 <superscript>+</superscript> T-cells and to the release of IL-16 from CD8 <superscript>+</superscript> lymphocytes.<br /> (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Analgesia methods
Animals
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Chemokine CCL4 immunology
Chemokine CCL4 pharmacology
Flow Cytometry methods
Hot Temperature
Male
Mice
Naloxone pharmacology
Pain metabolism
Receptors, CCR5 metabolism
Chemokine CCL4 metabolism
Hyperalgesia metabolism
Nociception drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 291
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34999112
- Full Text :
- https://doi.org/10.1016/j.lfs.2022.120302