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Involvement of calcitonin gene-related peptide and CCL2 production in CD40-mediated behavioral hypersensitivity in a model of neuropathic pain

Published online by Cambridge University Press:  01 March 2012

Jennifer T. Malon ,
Swathi Maddula ,
Harmony Bell  and
Ling Cao
Jennifer T. Malon
Affiliation:
Department of Microbiology, Biomedical Sciences Section, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA
Swathi Maddula
Affiliation:
Department of Microbiology, Biomedical Sciences Section, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA
Harmony Bell
Affiliation:
Department of Microbiology, Biomedical Sciences Section, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA
Ling Cao*
Affiliation:
Department of Microbiology, Biomedical Sciences Section, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA
*
Correspondence should be addressed to: Ling Cao, Department of Microbiology, Biomedical Sciences Section, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA phone: +1 207 602 2213 fax: +1 207 602 5931 email: lcao@UNE.edu
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Abstract

The neuropeptide calcitonin gene-related peptide (CGRP) is known to play a pro-nociceptive role after peripheral nerve injury upon its release from primary afferent neurons in preclinical models of neuropathic pain. We previously demonstrated a critical role for spinal cord microglial CD40 in the development of spinal nerve L5 transection (L5Tx)-induced mechanical hypersensitivity. Herein, we investigated whether CGRP is involved in the CD40-mediated behavioral hypersensitivity. First, L5Tx was found to significantly induce CGRP expression in wild-type (WT) mice up to 14 days post-L5Tx. This increase in CGRP expression was reduced in CD40 knockout (KO) mice at day 14 post-L5Tx. Intrathecal injection of the CGRP antagonist CGRP8–37 significantly blocked L5Tx-induced mechanical hypersensitivity. In vitro, CGRP induced glial IL-6 and CCL2 production, and CD40 stimulation added to the effects of CGRP in neonatal glia. Further, there was decreased CCL2 production in CD40 KO mice compared to WT mice 21 days post-L5Tx. However, CGRP8–37 did not significantly affect spinal cord CCL2 production following L5Tx in WT mice. Altogether, these data suggest that CD40 contributes to the maintenance of behavioral hypersensitivity following peripheral nerve injury in part through two distinct pathways, the enhancement of CGRP expression and spinal cord CCL2 production.

Keywords

Spinal nerve L5 transectiongliachemokinecytokineCCL2
Type
Research Article
Information
Neuron Glia Biology , Volume 7 , Issue 2-4 , May 2011 , pp. 117 - 128
Copyright
Copyright © Cambridge University Press 2012

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