Phenotypic Identification Of Spinal Cord-Infiltrating CD4+ T Lymphocytes In A Murine Model Of Neuropathic Pain

Draleau KS; Maddula S; Slaiby A; Nutile-McMenemy N; De Leo JA; Cao L

doi:10.4172/2167-0846.S3-003

ISSN: 2167-0846

Journal of Pain & Relief

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Phenotypic Identification Of Spinal Cord-Infiltrating CD4+ T Lymphocytes In A Murine Model Of Neuropathic Pain

Draleau KS¹, Maddula S¹, Slaiby A¹, Nutile-McMenemy N², De Leo JA^2,3 and Cao L^1*
¹Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME, 04005, USA
²Department of Anesthesiology, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA
³Vice President of Academic Affairs, Professor of Biology, Emmanuel College, 400 The Fenway, Boston, MA 02215, USA
Corresponding Author :	Ling Cao Department of Biomedical Science, College of Osteopathic Medicine University of New England, 11 Hills Beach Road Biddeford, ME 04005, USA Tel: +1-207-602-2213 Fax: +1-207-602-5931 E-mail: lcao@UNE.edu
Received January 28, 2014; Accepted February 17, 2014; Published February 19, 2014
Citation: Draleau KS, Maddula S, Slaiby A, Nutile-McMenemy N, De Leo JA, et al. (2014) Phenotypic Identification of Spinal Cord-Infiltrating CD4+ T Lymphocytes in a Murine Model of Neuropathic Pain. J Pain Relief S3:003. doi: 10.4172/2167-0846.S3-003
Copyright: © 2014 Draleau KS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Abstract

Background: Neuropathic pain is one of the most devastating kinds of chronic pain. Neuroinflammation has been shown to contribute to the development of neuropathic pain. We have previously demonstrated that lumbar spinal cord-infiltrating CD4+ T lymphocytes contribute to the maintenance of mechanical hypersensitivity in spinal nerve L5 transection (L5Tx), a murine model of neuropathic pain. Here, we further examined the phenotype of the CD4+ T lymphocytes involved in the maintenance of neuropathic pain-like behavior via intracellular flow cytometric analysis and explored potential interactions between infiltrating CD4+ T lymphocytes and spinal cord glial cells.

Results: We consistently observed significantly higher numbers of T-Bet+ , IFNγ+, TNFα+, and GM-CSF+, but not GATA3+ or IL-4+, lumbar spinal cord-infiltrating CD4+ T lymphocytes in the L5Tx group compared to the sham group at day 7 post-L5Tx. This suggests that the infiltrating CD4+ T lymphocytes expressed a pro-inflammatory type 1 phenotype (Th1). Despite the observation of CD4+ CD40 ligand (CD154)+ T lymphocytes in the lumbar spinal cord post-L5Tx, CD154 knockout (KO) mice did not display significant changes in L5Tx-induced mechanical hypersensitivity, indicating that T lymphocyte-microglial interaction through the CD154-CD40 pathway in not necessary for L5Tx-induced hypersensitivity. In addition, spinal cord astrocytic activation, represented by glial fibillary acidic protein (GFAP) expression, was significantly lower in CD4 KO mice compared to wild type (WT) mice at day 14 post-L5Tx, suggesting the involvement of astrocytes in the pronociceptive effects mediated by infiltrating CD4+ T lymphocytes.

Conclusions: In all, these data indicate that the maintenance of L5Tx-induced neuropathic pain is mostly mediated by Th1 cells in a CD154-independent manner via a mechanism that could involve multiple Th1 cytokines and astrocytic activation.

Draleau KS¹, Maddula S¹, Slaiby A¹, Nutile-McMenemy N², De Leo JA^2,3 and Cao L^1*
¹Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME, 04005, USA
²Department of Anesthesiology, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA
³Vice President of Academic Affairs, Professor of Biology, Emmanuel College, 400 The Fenway, Boston, MA 02215, USA
Corresponding Author :	Ling Cao Department of Biomedical Science, College of Osteopathic Medicine University of New England, 11 Hills Beach Road Biddeford, ME 04005, USA Tel: +1-207-602-2213 Fax: +1-207-602-5931 E-mail: lcao@UNE.edu
Received January 28, 2014; Accepted February 17, 2014; Published February 19, 2014
Citation: Draleau KS, Maddula S, Slaiby A, Nutile-McMenemy N, De Leo JA, et al. (2014) Phenotypic Identification of Spinal Cord-Infiltrating CD4+ T Lymphocytes in a Murine Model of Neuropathic Pain. J Pain Relief S3:003. doi: 10.4172/2167-0846.S3-003
Copyright: © 2014 Draleau KS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Draleau KS¹, Maddula S¹, Slaiby A¹, Nutile-McMenemy N², De Leo JA^2,3 and Cao L^1*
¹Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME, 04005, USA
²Department of Anesthesiology, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA
³Vice President of Academic Affairs, Professor of Biology, Emmanuel College, 400 The Fenway, Boston, MA 02215, USA
Corresponding Author :	Ling Cao Department of Biomedical Science, College of Osteopathic Medicine University of New England, 11 Hills Beach Road Biddeford, ME 04005, USA Tel: +1-207-602-2213 Fax: +1-207-602-5931 E-mail: lcao@UNE.edu
Received January 28, 2014; Accepted February 17, 2014; Published February 19, 2014
Citation: Draleau KS, Maddula S, Slaiby A, Nutile-McMenemy N, De Leo JA, et al. (2014) Phenotypic Identification of Spinal Cord-Infiltrating CD4+ T Lymphocytes in a Murine Model of Neuropathic Pain. J Pain Relief S3:003. doi: 10.4172/2167-0846.S3-003
Copyright: © 2014 Draleau KS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.