Complement activation contributes to leukocyte recruitment and neuropathic pain following peripheral nerve injury in rats
- 4 December 2007
- journal article
- Published by Wiley in European Journal of Neuroscience
- Vol. 26 (12), 3486-3500
- https://doi.org/10.1111/j.1460-9568.2007.05971.x
Abstract
Complement activation triggers inflammation and has been implicated in neurological diseases associated with pain. However, the role of complement in neuropathic pain has not been clearly defined. In this study, we tested whether complement is activated by partial ligation of the rat sciatic nerve, a widely used model of neuropathic pain, and whether complement activation or inhibition in peripheral nerve influences leukocyte recruitment and neuropathic pain. We found that C3 deposition significantly increased from 6 h to 7 days in the injured nerve and was associated with the extent of thermal hyperalgesia and mechanical allodynia. However, no deposition of the membrane attack complex was detected. Complement activation by endoneurial injection of aggregated rat immunoglobulin G into normal sciatic nerve produced significant thermal hyperalgesia and mechanical allodynia of the ipsilateral hindpaw at 2-7 days after injection. This was accompanied by increased deposition of C3 and recruitment of macrophages at 7 days following injection. Complement inhibition using systemic injections of soluble complement receptor 1 (AVANT Immunotherapeutics, Inc., Needham, USA) into rats markedly suppressed C3 deposition and T-cell and macrophage recruitment to the injured nerve, and produced significant alleviation of thermal hyperalgesia and mechanical allodynia. These results demonstrate that C3 activation in the nerve contributes to increased infiltration of inflammatory cells and to neuropathic pain behaviors following peripheral nerve injury. Complement inhibition may be a potential therapeutic treatment for neuropathic pain.Keywords
This publication has 55 references indexed in Scilit:
- Complement Induction in Spinal Cord Microglia Results in Anaphylatoxin C5a-Mediated Pain HypersensitivityJournal of Neuroscience, 2007
- T cell infiltration after chronic constriction injury of mouse sciatic nerve is associated with interleukin-17 expressionExperimental Neurology, 2006
- T lymphocytes play a role in neuropathic pain following peripheral nerve injury in ratsNeuroscience, 2004
- Immunopathology of secondary‐progressive multiple sclerosisAnnals of Neurology, 2001
- ComplementNew England Journal of Medicine, 2001
- ComplementNew England Journal of Medicine, 2001
- Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigmCell, 1994
- MHC-positive, ramified macrophages in the normal and injured rat peripheral nervous systemJournal of Neurocytology, 1992
- A-fibers mediate mechanical hyperesthesia and allodynia and C-fibers mediate thermal hyperalgesia in a new model of causalgiform pain disorders in ratsNeuroscience Letters, 1990
- Complement depletion suppresses Lewis rat experimental allergic neuritisBrain Research, 1987