| Abstract No.: | B-C2080 |
| Country: | Canada |
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| Title: | MCP-1, A SELECTIVE CCR2 AGONIST, INCREASES THE EXCITABILITY OF CULTURED NEUROPATHIC DRG NEURONS |
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| Authors/Affiliations: | 1 Claudia Jomphe*; 1 Xiang Wan; 1 Michel Paré; 1 Martin Perkins; 1 Chang Qing Cao;
1 AstraZeneca R&D Montréal, QC, Canada
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| Content: | Recently, it has been shown that MCP-1/CCL2 and its C-C chemokine receptor (CCR2) are up-regulated in neuropathic DRG neurons (White et al., 2005). The aim of the present study was to test the hypothesis that CCR2 receptor could mediate the excitability of nociceptive dorsal root ganglia (DRG) neurons after neuropathic injury induced by a chronic constriction (CCI) of the sciatic nerve. Electrophysiological recordings in whole-cell current clamp mode were performed on cultured DRG neurons from day 2 to 5 after their isolation. Lumbar DRG neurons were isolated from CCI rats, 11 to 19 days post surgery. A local application of rat MCP-1/CCL2 significantly increases both the spontaneous and evoked firing rate of a subset of capsaicin-sensitive neuropathic DRG neurons. The proportion of responsive nociceptors was increased in a time-dependent fashion following the CCI surgery. The excitatory effect of MCP-1/CCL2 on neuropathic DRG neurons was dose-dependent. Indeed, a local application of 50 nM and 100 nM MCP-1/CCL2 produced a 37 ±10% and 46 ± 13% enhancement respectively in the evoked firing rate, while no effect was seen with the highest dose in DRG neurons isolated from sham rats. Taken together, these results suggest that the chemokine MCP-1/CCL2 has a direct excitatory effect on neuropathic DRG neurons. Since MCP-1/CCL2 is a highly selective ligand for CCR2 receptor, this excitatory effect is likely to be mediated by the activation CCR2 receptors. |
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