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.
Keywords:
CCL5; Calcitonin gene-related peptide (CGRP); Neuropathic pain; Spinal cord; Spinal nerve L5 transection; p38.
Copyright © 2016 Elsevier B.V. All rights reserved.
MeSH terms
-
Animals
-
Antibodies / pharmacology
-
Calcitonin Gene-Related Peptide / metabolism*
-
Calcitonin Gene-Related Peptide / therapeutic use
-
Cells, Cultured
-
Chemokine CCL5 / immunology
-
Chemokine CCL5 / metabolism*
-
Cytokines / metabolism
-
Disease Models, Animal
-
Enzyme Inhibitors / pharmacology
-
Female
-
Hyperalgesia / drug therapy
-
Hyperalgesia / etiology*
-
Hyperalgesia / metabolism*
-
Imidazoles / pharmacology
-
MAP Kinase Signaling System / drug effects
-
MAP Kinase Signaling System / physiology*
-
Male
-
Mice
-
Mice, Inbred BALB C
-
Neuroglia / drug effects
-
Neuroglia / metabolism
-
Pain Threshold / drug effects
-
Peptide Fragments / therapeutic use
-
Peripheral Nerve Injuries / complications*
-
Pyridines / pharmacology
-
Spinal Cord / cytology
-
Spinal Cord / metabolism
-
Spinal Nerves / pathology
Substances
-
Antibodies
-
Chemokine CCL5
-
Cytokines
-
Enzyme Inhibitors
-
Imidazoles
-
Peptide Fragments
-
Pyridines
-
calcitonin gene-related peptide (8-37)
-
Calcitonin Gene-Related Peptide
-
SB 203580