Endogenous analgesia mediated by CD4(+) T lymphocytes is dependent on enkephalins in mice

• Published in: Journal of neuroinflammation 2016-06, Vol.13 (1), p.132-132, Article 132
• Main Authors: Basso, Lilian, Boué, Jérôme, Mahiddine, Karim, Blanpied, Catherine, Robiou-du-Pont, Sébastien, Vergnolle, Nathalie, Deraison, Céline, Dietrich, Gilles
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analgesia - methods; Animals; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Chronic pain; Enkephalins; Enkephalins - genetics; Enkephalins - immunology; Enkephalins - metabolism; Immunoglobulin G; Influence; Life Sciences; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Pain - immunology; Pain - metabolism; Pain - prevention & control; Pain Measurement - methods; Rabbits; Random Allocation; Risk factors
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-016-0591-x

T cell-derived opioids play a key role in the control of inflammatory pain. However, the nature of opioids produced by T cells is still matter of debate in mice. Whereas β-endorphin has been found in T lymphocytes by using antibody-based methods, messenger RNA (mRNA) quantification shows mainly mRNA encoding for enkephalins. The objective of the study is to elucidate the nature of T cell-derived opioids responsible for analgesia and clarify discrepancy of the results at the protein and genetic levels. CD4(+) T lymphocytes were isolated from wild-type and enkephalin-deficient mice. mRNA encoding for β-endorphin and enkephalin was quantified by RT-qPCR. The binding of commercially available polyclonal anti-endorphin antibodies to lymphocytes from wild-type or enkephalin knockout mice was assessed by cytofluorometry. Opioid-mediated analgesic properties of T lymphocytes from wild-type and enkephalin-deficient mice were compared in a model of inflammation-induced somatic pain by measuring sensitivity to mechanical stimuli using calibrated von Frey filaments. CD4(+) T lymphocytes expressed high level of mRNA encoding for enkephalins but not for β-endorphin in mice. Anti-β-endorphin polyclonal IgG antibodies are specific for β-endorphin but cross-react with enkephalins. Anti-β-endorphin polyclonal antibodies bound to wild-type but not enkephalin-deficient CD4(+) T lymphocytes. Endogenous regulation of inflammatory pain by wild-type T lymphocytes was completely abolished when T lymphocytes were deficient in enkephalins. Pain behavior of immune-deficient (i.e., without B and T lymphocytes) mice was superimposable to that of mice transferred with enkephalin-deficient lymphocytes. Rabbit polyclonal anti-β-endorphin serum IgG bind to CD4(+) T lymphocytes because of their cross-reactivity towards enkephalins. Thus, staining of T lymphocytes by anti-β-endorphin polyclonal IgG reported in most of studies in mice is because of their binding to enkephalins. In mice, CD4(+) T lymphocytes completely lose their analgesic opioid-mediated activity when lacking enkephalins.