Implication of the chemokine CCL2 in trigeminal nociception and traumatic neuropathic orofacial pain.

Abstract

BACKGROUND:

Chemokine (C-C motif) ligand 2 (CCL2) participates in different mechanisms contributing to the spinal cord inflammation and pain development after sciatic nerve injury. Recent data also support its role in orofacial thermal hypersensitivity, although its implication in different phases of trigeminal pain emergence is unclear. We assessed the importance of CCL2 signalling in biochemical and behavioural alterations during the early and late stages following chronic constriction injury of infraorbital nerve (ION-CCI), a model of peripheral traumatic trigeminal pain.

METHODS:

After evaluating the consequences of CCL2 intracisternal injection in naïve rats, we determined the expression changes for CCL2, inflammatory and glia activation markers in the somatosensory trigeminal complex (STC) and trigeminal ganglia (TG) after ION-CCI. The role of CCL2 signalling was assessed using pre-emptive or 'curative' intracisternal treatment with specific CCL2 receptor antagonist - INCB3344.

RESULTS:

Exogenous CCL2 evoked spontaneous behaviour reminiscent of orofacial pain and marked mechanical hypersensitivity, associated with increased expression of proinflammatory cytokines and glial markers in STC and TG. CCL2-evoked changes were prevented by the co-administration of INCB3344. Two weeks after ION-CCI, mRNA for CCL2, glial and inflammatory markers were up-regulated, and CCL2-immunoreactivity accumulated in central and ganglionic tissues. At this time, repeated intracisternal administration of INCB3344 did not attenuate the ION-CCI-associated behavioural nor biochemical changes. By contrast, pre-emptive INCB3344 treatment delayed the emergence of trigeminal mechanical allodynia and associated biochemical alterations.

CONCLUSIONS:

Our data suggest that CCL2 is involved principally in the early events accompanying the ION lesion rather than in long-term alterations and the maintenance of trigeminal mechanical hypersensitivity.

• Authors: C Dauvergne, J Molet, A Reaux-Le Goazigo, A Mauborgne, S Mélik-Parsadaniantz, Y Boucher, M Pohl
• Journal: European journal of pain (London, England) (Eur J Pain) Vol. 18 Issue 3 Pg. 360-75 (Mar 2014) ISSN: 1532-2149 [Electronic] England
• PMID: 23918315 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 European Pain Federation - EFIC®

Chemical References

• Ccr2 protein, rat
• Chemokine CCL2
• INCB3344
• Pyrrolidines
• Receptors, CCR2

Topics

• Animals
• Chemokine CCL2 (metabolism, pharmacology)
• Facial Pain (metabolism)
• Hyperalgesia (metabolism)
• Male
• Neuralgia (metabolism)
• Nociception (physiology)
• Pyrrolidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, CCR2 (antagonists & inhibitors)
• Signal Transduction (drug effects)
• Trigeminal Ganglion (drug effects, metabolism)