Neuroanatomical and functional evidence that the chemokine CXCL12 (SDF-1) and its receptor CXCR4 are involved in nociception at the spinal level
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1
Université Pierre et Marie Curie, UMRS INSERM UPMC 713, Faculte de Medecine Pitie-Salpetriere, France
Chemokines are secreted proteins classically implicated in immune and inflammatory functions. However, growing evidences reveal that chemokines are also produced in the central and peripheral nervous systems and play an important role in pain modulation. The aim of the present study was therefore to investigate whether the Stromal cell-derived factor SDF-1/CXCL12 is directly involved in pain transmission at the spinal level in rats. We first established, using immunohistochemical techniques, that CXCL12 and CXCR4 were extensively associated with spinal nociceptive pathways, both in the dorsal root ganglia (DRGs) and in the superficial layers of the dorsal horn of the normal rat spinal cord. We then examined the effects of intrathecal (i.t.) administration of CXCL12 on the nociceptive response to tactile stimuli. I.t. administration of CXCL12 at a dose of 1 µg progressively induced mechanical allodynia; lowering the paw-withdrawal threshold to Von Frey filament from 40 g to 30 g. Changes in non-noxious tactile threshold were maintained over 6 days after CXCL12 treatment. To assess whether the CXCL12 effects were attributable to a selective stimulation of CXCR4 receptors, rats were concomitantly treated with CXCL12 and the CXCR4 antagonist (AMD 3100). A single injection of 1 mM AMD 3100 significantly blocked the development of CXCL12 - induced mechanical allodynia. Altogether, these results demonstrate that CXCL12 is constitutively expressed by ascending nociceptive structures and is directly implicated in the neurotransmission of painful stimuli, probably by its binding to CXCR4 receptors.
Supported by ANR and INSERM.
Conference:
3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009.
Presentation Type:
Oral Presentation
Topic:
Symposium 17 – Chemokines: new modulators in brain and pituitary functions
Citation:
Goazigo
AR,
Pohl
M and
Parsadaniantz
SM
(2009). Neuroanatomical and functional evidence that the chemokine CXCL12 (SDF-1) and its receptor CXCR4 are involved in nociception at the spinal level.
Front. Neurosci.
Conference Abstract:
3rd Mediterranean Conference of Neuroscience .
doi: 10.3389/conf.neuro.01.2009.16.072
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Received:
20 Nov 2009;
Published Online:
20 Nov 2009.
*
Correspondence:
Stephane M Parsadaniantz, Université Pierre et Marie Curie, UMRS INSERM UPMC 713, Faculte de Medecine Pitie-Salpetriere, Paris, France, Stephane.Melik-Parsadaniantz@inserm.fr