Journal
PAIN
Volume 149, Issue 2, Pages 305-315Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.pain.2010.02.025
Keywords
MIP-1 alpha; CCR1; CCR5; IL-1 beta; Neuropathic pain; Chemokine
Categories
Funding
- Japan Society for the Promotion of Science (JSPS) [19659404]
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) [21791469]
- Grants-in-Aid for Scientific Research [19659404, 21791469] Funding Source: KAKEN
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In the present study, we investigated the role of the macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the pathogenesis of neuropathic pain following partial sciatic nerve ligation (PSL) in mice. MIP-1 alpha mRNA and its protein were dramatically up-regulated after PSL, and MIP-1 alpha was localized on macrophages and Schwann cells in the injured sciatic nerve (SCN). PSL-induced long-lasting tactile allodynia and thermal hyperalgesia were prevented by the perineural injection of anti-MIP-1 alpha (2 ng). Intraneural (20 ng) and perineural (100 ng) injection of recombinant MIP-1 alpha elicited tactile allodynia and thermal hyperalgesia in sham-operated limb. MIP-1 alpha receptors (CCR1 and CCR5) mRNA and their proteins were also up-regulated in the SCN after PSL, and were localized on macrophages and Schwann cells. PSL-induced tactile allodynia was attenuated by perineural injection (0.2 nmol) of siRNA against CCR1 and CCR5. On the other hand, PSL-induced thermal hyperalgesia was prevented by siRNA against CCR5, but not CCR1. Interleukin- 1 beta (IL-1 beta) mRNA and its precursor protein in macrophages and Schwann cells were also up-regulated in the SCN after PSL, and PSL-induced neuropathic pain was prevented by the perineural injection of anti-IL-1 beta (2 ng). PSL-induced IL-1 beta up-regulation was suppressed by anti-MIP-1 alpha and siRNA against CCR1 and CCR5. Perineural injection of nicotine (20 nmol), a macrophage suppressor, prevented PSL-induced neuropathic pain and suppressed MIP-1 alpha and IL-1 beta expressions. In conclusion, we propose a novel critical molecule MIP-1 alpha derived from macrophages and Schwann cells that appears to play a crucial role in the development of neuropathic pain induced by PSL. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
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