CCL2 has similar excitatory effects to TNF-α in a subgroup of inflamed C-fiber axons

Richards, Natalie, Batty, Thomas and Dilley, Andrew (2011) CCL2 has similar excitatory effects to TNF-α in a subgroup of inflamed C-fiber axons. Journal of Neurophysiology, 106 (6). pp. 2838-2848. ISSN 0022-3077

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Peripheral nerve inflammation can cause neuronal excitability changes that have been implicated in the pathogenesis of chronic pain. Although the neuroimmune interactions that lead to such physiological changes are unclear, in vitro studies suggest that the chemokine CCL2 may be involved. This in vivo study examines the effects of CCL2 on untreated and inflamed neurons and compares its effects with those of TNF-α. Extracellular recordings were performed in the anesthetized rat on isolated neurons with C-fiber axons. On untreated neurons, CCL2, as well as TNF-α, had negligible effects. Following neuritis, both cytokines transiently caused the firing of action potentials in 27–30% of neurons, which were either silent or had background (ongoing) activity. The neurons with ongoing activity, which responded to either cytokine, had significantly slower baseline firing rates {median = 3.0 spikes/min [interquartile range (IQR) 3.0]} compared with the nonresponders [median = 24.4 spikes/min (IQR 24.6); P < 0.001]. In an additional group, 26–27% of neurons, which were sensitized due to repeated noxious mechanical stimulation of the periphery, also responded to the effects of both cytokines. Neither cytokine caused axons to become mechanically sensitive. Immunohistochemistry confirmed that the cognate CCL2 receptor, CCR2, is mainly expressed on glia and is therefore not likely to be an axonal target for CCL2 following inflammation. In contrast, the cognate TNF-α receptor (TNFR), TNFR1, was present on untreated and inflamed neurons. In summary, CCL2 can excite inflamed C-fiber neurons with similar effects to TNF-α, although the underlying mechanisms may be different. The modulatory effects of both cytokines are limited to a subgroup of neurons, which may be subtly inflamed.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Brighton and Sussex Medical School > Division of Medical Education
Subjects: R Medicine > RC Internal medicine > RC0581 Specialties of internal medicine > RC1200 Sports medicine
Depositing User: Ellen Thomas
Date Deposited: 31 Oct 2012 15:46
Last Modified: 25 Sep 2017 09:05
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