Trigeminal injury causes kappa opioid-dependent allodynic, glial and immune cell responses in mice

Abstract Background The dynorphin-kappa opioid receptor (KOR) system regulates glial proliferation after sciatic nerve injury. Here, we investigated its role in cell proliferation following partial ligation of infraorbital nerve (pIONL), a model for trigeminal neuropathic pain. Mechanical allodynia was enhanced in KOR gene deleted mice (KOR-/-) compared to wild type mice. Using bromodeoxyuridine (BrdU) as a mitotic marker, we assessed cell proliferation in three different areas of the trigeminal afferent pathway: trigeminal nucleus principalis (Vp), trigeminal root entry zone (TREZ), and trigeminal ganglion (TG). Results In KOR-/- mice or norBNI-treated mice, the number of proliferating cells in the Vp was significantly less than in WT mice, whereas cell proliferation was enhanced in TREZ and TG. The majority of the proliferating cells were nestin positive stem cells or CD11b positive microglia in the Vp and macrophages in the TG. GFAP-positive astrocytes made a clear borderline between the CNS and the PNS in TREZ, and phosphorylated KOR staining (KOR-p) was detectable only in the astrocytes in CNS in WT mice but not in KOR-/- or norBNI-treated mice. Conclusions These results show that kappa opioid receptor system has different effects after pIONL in CNS and PNS: KOR activation promotes CNS astrocytosis and microglial or stem cell proliferation but inhibits macrophage proliferation in PNS. The trigeminal central root has a key role in the etiology and treatment of trigeminal neuralgia, and these newly identified responses may provide new targets for developing pain therapies

Erythrocyte autoimmune disorder: red cell antibodies and the human allogeneic rosette test

A new test termed the human allogeneic rosette test (HART) is reported for the detection of small amounts of erythrocyte autoantibodies. It compares the percentage of rosettes formed around lymphocytes from normal subjects when either red cells from patients are added or autologous or allogeneic normal red cells. The HART is positive when the percentage of rosettes made with the control's red blood cells is significantly more than the percentage of those made with the patient's red blood cells. Twenty-two out of twenty-six patients with a positive antiglobulin test had a positive HART. Thirty patients with a negative antiglobulin test but with clinical or biological data suggesting an erythrocyte autoimmune disorder were also studied with the HART. Out of sixteen patients with chronic lymphatic leukaemia, ten had a positive test; all three patients with idiopathic thrombocytopenic purpura showed a positive HART; two out of three patients with cirrhosis and one out of four patients with Hodgkin's disease also had a positive test. No correlation was found between the positivity of the HART in these patients and their haematological values. Two patients with suspected autoimmune haemolytic anaemia and with a negative anti-globulin test but a positive HART were treated with steroids. Both responded very rapidly to the treatment suggesting an immune origin for the anaemia. The HART has been reproduced experimentally. Normal human red blood cells, sensitized with different amounts of either an auto-antibody or anti-D were rosetted with autologous normal lymphocytes. The results showed that the percentage of rosettes with red cells coated with small amounts of antibody was significantly less than the percentage of rosettes with uncoated red cells. A plot of these results seemed to indicate that the HART was about twenty times more sensitive than the antiglobulin test. The nature of the cells involved in the positive HART-negative direct antiglobulin test red cell binding was also analysed. They appear to be related to the T cell population. The role of the receptors for IgG in the HART was demonstrated by showing that aggregated and non-aggregated human IgG could inhibit the HART phenomenon. In conclusion, the HART appears to be a new and sensitive immunological test capable of analysing erythrocyte autoimmune disorders

Levamisole and human lymphocyte surface markers.

The action of various concentrations of levamisole on normal human lymphocytes was investigated in vitro. The action of levamisole (10(-1) mg-10(-8) mg%) upon rosette formation was studied using two rosette assays with SRBC (the active and the total T-rosette tests) to quantify T cells and the EAC assay to quantify B cells. Levamisole at only 10(-3) mg% significantly increased the percentage of both active and total T cells. In sharp contrast, levamisole between 10(-2) and 10(-7) mg% significantly decreased the EAC percentage. It is concluded that levamisole promotes a better expressivity of T-cell receptor and decreases the expressivity of C3 receptor

Immune Signals Involved in Cyclosporine and Methylprednisolone Inhibition of A23187 Ionophore Induced Proliferation

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Depletion of lymphocytes with membrane markers of helper phenotype: a feature of acute and chronic drug-induced immunosuppression.

T cell subsets tested with markers for Fc receptors for Ig (TM, TG and EAhu rosettes) or monoclonal antibodies (T4 and T8 lymphocytes) were investigated both in normal volunteers and in kidney transplant recipients with a well functioning graft and receiving low immunosuppressive therapy, before and 4 hr after administration of 100 mg of hydrocortisone. Hydrocortisone induced a redistribution which was characterized by a decrease in the percentages of TM (38 +/- 2.4 before; 22 +/- 2.9 after; P less than 0.0005) and T4 (48 +/- 2.6 before; 35.8 +/- 2.7 after; P less than 0.0025) lymphocytes. Transplanted patients under chronic immunosuppression already disclosed a reduction of the percentages of TM (19.4 +/- 2.6; P less than 0.005) and T4 (41.1 +/- 3.6; P less than 0.05) lymphocytes before the administration of hydrocortisone when compared to the values obtained in normals. Moreover, significant decrease of percentages of TM lymphocytes (19.4 +/- 2.6 before; 12.8 +/- 2.6 after; P less than 0.01) were obtained after hydrocortisone injection. In contrast, T8, TG and EAhu rosettes percentages were characterized by a relative resistance to immunosuppressive agents--the only exception being TG lymphocytes in transplant recipients. It is concluded that TM and T4 depletion is a common feature of acute and chronic drug-induced immunosuppression, suggesting that helper-inducer cells are important targets for immunosuppressive therapy