Abstract | BACKGROUND: RESULTS: Focal nerve demyelination increased behavioral reflex responsiveness to mechanical stimuli between postoperative day (POD) 3 and POD28 in both the hindpaw ipsilateral and contralateral to the nerve injury. This behavior was accompanied by a bilateral increase in the numbers of primary sensory neurons expressing the chemokine receptors CCR2, CCR5, and CXCR4 by POD14, with no change in the pattern of CXCR3 expression. Significant increases in the numbers of neurons expressing the chemokines monocyte chemoattractant protein-1 (MCP-1/CCL2), Regulated on Activation, Normal T Expressed and Secreted ( RANTES/CCL5) and interferon gamma-inducing protein-10 (IP-10/CXCL10) were also evident following nerve injury, although neuronal expression pattern of stromal cell derived factor-1alpha (SDF1/CXCL12) did not change. Functional studies demonstrated that acutely dissociated sensory neurons derived from LPC-injured animals responded with increased [Ca2+]i following exposure to MCP-1, IP-10, SDF1 and RANTES on POD 14 and 28, but these responses were largely absent by POD35. On days 14 and 28, rats received either saline or a CCR2 receptor antagonist isomer (CCR2 RA-[R]) or its inactive enantiomer (CCR2 RA-[S]) by intraperitoneal (i.p.) injection. CCR2 RA-[R] treatment of nerve-injured rats produced stereospecific bilateral reversal of tactile hyperalgesia. CONCLUSION: These results suggest that the presence of chemokine signaling by both injured and adjacent, uninjured sensory neurons is correlated with the maintenance phase of a persistent pain state, suggesting that chemokine receptor antagonists may be an important therapeutic intervention for chronic pain.
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Authors | Sonia Bhangoo, Dongjun Ren, Richard J Miller, Kenneth J Henry, Jayana Lineswala, Chafiq Hamdouchi, Baolin Li, Patrick E Monahan, David M Chan, Matthew S Ripsch, Fletcher A White |
Journal | Molecular pain
(Mol Pain)
Vol. 3
Pg. 38
(Dec 12 2007)
ISSN: 1744-8069 [Electronic] United States |
PMID | 18076762
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Animals
- Demyelinating Diseases
(metabolism, pathology)
- Female
- Ganglia, Spinal
(pathology)
- Immunohistochemistry
- In Situ Hybridization
- Neurons
(metabolism, physiology)
- Nociceptors
(metabolism)
- Pain
(metabolism, pathology)
- Rats
- Rats, Sprague-Dawley
- Receptors, Chemokine
(antagonists & inhibitors, metabolism)
- Sciatic Nerve
(metabolism, pathology)
- Up-Regulation
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