Global gene expression analysis in the mouse brainstem after hyperalgesia induced by facial carrageenan injection--evidence for a form of neurovascular coupling?
The present study was carried out to examine global gene expression in the brainstem, in a mouse facial carrageenan injection model of orofacial pain. Mice that received facial carrageenan injection showed increased mechanical allodynia, demonstrated by increased responses to von Frey hair stimulation of the face. The brainstem was harvested at 3 days post-injection, corresponding to the time of peak responses, and analyzed by Affymetrix Mouse Genome 430 2.0 microarrays. We sought to identify common genes that are changed in the respective sides of the brainstem after either right- or left-sided facial carrageenan injection. The result is a relatively small list of genes (22 genes), which were then classified using DAVID software. Many of them fell into the categories of "response to stress", "defence response", "response to biotic stimulus", "cell adhesion" and "leukocyte adhesion". Of these, increased expression of P-selectin, ICAM-1 and CCL12 after carrageenan injection could be verified by real-time RT-PCR on both the right and left sides, and increased in P-selectin and ICAM-1 further verified by Western blot analysis. P-selectin and ICAM-1 were immunolocalized to endothelial cells, and were double labelled with von Willebrand factor. Intraperitoneal injection of the P-selectin inhibitor KF38789 significantly reduced mechanical allodynia in the facial carrageenan-injected mice. P-selectin mediates the capturing of leukocytes from the bloodstream and rolling of leukocytes along the endothelial surface. We hypothesize that increased nociceptive input to the brainstem could attract circulating macrophages into the brain, resulting in neuroinflammation and pain.
Poh
Kay-Wee
KW
Department of Oral and Maxillofacial Surgery, National University of Singapore, Singapore 119260, Singapore.
Lutfun
Nahar
N
Manikandan
Jayapal
J
Ong
Wei-Yi
WY
Yeo
Jin-Fei
JF
D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D002351:Carrageenan / Q000009:adverse effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005145:Face / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011753:Pyrones / Q000008:administration & dosage
C090509:Icam1 protein, mouse; C453959:KF38789; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D011753:Pyrones; C028254:von Willebrand factor receptor; D018799:Intercellular Adhesion Molecule-1; D002351:Carrageenan