title: Endogenous opioid-mediated analgesia is dependent on adaptive T cell response in mice.
abstract: Pain is an inherent component of inflammation often accompanying immune response. A large spectrum of molecules released within the inflamed tissue induces pain by stimulating primary afferent neurons in situ. Activity of primary sensitive fibers can be counteracted by local opioid release by leukocytes. In this study, we investigated the endogenous regulation of CFA-induced inflammatory pain in the context of adaptive T cell immune response. The nociceptive response to mechanical stimuli was studied using von Frey filaments in mice immunized with OVA in CFA. The nociceptive response of nude versus wild-type mice was dramatically increased, demonstrating T cell deficiency associated with increased pain sensitivity. Based on adoptive transfer experiments of OVA-specific CD4(+) T lymphocytes into nude mice, we show that Ag-specific activated, but not resting T lymphocytes are responsible for the spontaneous relief of inflammation-induced pain following Ag challenge. The analgesia was dependent on opioid release by Ag-primed CD4(+) T lymphocytes at the inflammatory site. Indeed, T cell-mediated analgesia was inhibited by local injection of an opioid receptor antagonist, unable to cross the blood-brain barrier. Notably, we found opioid precursor mRNA to be >7-fold increased in Ag-specific activated CD4(+) T lymphocytes, as compared with resting T lymphocytes in vivo. Taken together, our results show that CD4(+) T lymphocytes acquire antinociceptive effector properties when specifically primed by Ag and point out analgesia as a property linked to the effector phase of adaptive T cell response.
authors.affiliation: INSERM 1043, Centre de Physiopathologie de Toulouse-Purpan, F-31300 Toulouse, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Boué
authors.forename: Catherine
authors.initials: C
authors.lastname: Blanpied
authors.forename: Pierre
authors.initials: P
authors.lastname: Brousset
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vergnolle
authors.forename: Gilles
authors.initials: G
authors.lastname: Dietrich
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D018847:Opioid Peptides / Q000276:immunology*; D010146:Pain / Q000209:etiology / Q000276:immunology*; D016133:Polymerase Chain Reaction
chemical_list: D018847:Opioid Peptides