Induction of CX3CL1 expression in astrocytes and CX3CR1 in microglia in the spinal cord of a rat model of neuropathic pain.
Previous studies have shown that chemokines might play a role in the pathology of chronic pain. The purpose of this study was to provide an immunohistochemical description of the distribution of CX3CL1 (fractalkine) and its receptor CX3CR1 in the rat spinal cord in a model of inflammatory pain induced by unilateral intraplantar complete Freund's adjuvant (CFA) and in a model of neuropathic pain induced by L5 spinal nerve ligation (modified Chung model or mSNL). In naïve rats, CX3CL1 is found in the cytoplasm of neurons as shown by colocalization of CX3XL1 and NeuN. Similar distribution of CX3CL1 was observed after CFA, whereas after mSNL, CX3CL1 was not only observed in neurons but also found in astrocytes, as shown by colocalization of CX3CL1 and GFAP. Weak immunoreactivity for the CX3CL1 receptor, CX3CR1, was found in microglia in the spinal cord of either naïve rats or rats with inflammation. However, after spinal nerve injury, CX3CR1-LI was upregulated in microglia throughout the dorsal horn.


CONCLUSIONS
This study shows that spinal nerve injury, but not peripheral inflammation, induces the expression of a chemokine, CX3CL1 (fractalkine), in astrocytes and upregulates CX3CR1 in microglia in the spinal cord. This selective regulation of CX3CL1 and its receptor, CX3CR1, suggests that these chemokines may represent new targets for the treatment of neuropathic pain.
Department of Pharmacology, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Jill A
JA
Lindia
Erin
E
McGowan
Nina
N
Jochnowitz
Catherine
C
Abbadie
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000378:metabolism*; D004195:Disease Models, Animal; D005620:Freund's Adjuvant; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018121:Receptors, Cytokine / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology; D013127:Spinal Nerves / Q000293:injuries / Q000601:surgery; D015854:Up-Regulation / Q000502:physiology
D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D008565:Membrane Proteins; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D005620:Freund's Adjuvant