title: Calcitonin gene-related peptide contributes to peripheral nerve injury-induced mechanical hypersensitivity through CCL5 and p38 pathways.
abstract: The role of calcitonin gene related peptide (CGRP) in neuropathic pain was investigated in a mouse model of neuropathic pain, spinal nerve L5 transection (L5Tx). Intrathecal injection (i.t.) of CGRP8-37, a CGRP antagonist, significantly reduced L5Tx-induced mechanical hypersensitivity and lumbar spinal cord CCL5 expression. i.t. injection of a CCL5 neutralizing antibody significantly inhibited L5Tx-induced mechanical hypersensitivity. Further, pre-treatment with a p38-inhibitor, SB203580, was able to reduce CGRP-induced mechanical hypersensitivity, but not CGRP-induced CCL5 production. Our data indicate that CGRP can play its pro-nociceptive role through both a spinal cord CCL5-dependent, p38-independent pathway, and a p38-depenented, CCL5-independent pathway.
authors.affiliation: Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, 11 Hills Beach Road, ME 04005, USA. Electronic address: jmalon@UNE.edu.
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Malon
authors.affiliation: Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, 11 Hills Beach Road, ME 04005, USA. Electronic address: lcao@UNE.edu.
authors.forename: Ling
authors.initials: L
authors.lastname: Cao
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000627:therapeutic use; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects; D010446:Peptide Fragments / Q000627:therapeutic use; D059348:Peripheral Nerve Injuries / Q000150:complications*; D011725:Pyridines / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013127:Spinal Nerves / Q000473:pathology
chemical_list: D000906:Antibodies; D018946:Chemokine CCL5; D016207:Cytokines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide; C093642:SB 203580
keywords: CCL5; Calcitonin gene-related peptide (CGRP); Neuropathic pain; Spinal cord; Spinal nerve L5 transection; p38