title: Astrocytes are involved in trigeminal dynamic mechanical allodynia: potential role of D-serine.
abstract: Trigeminal neuropathic pain affects millions of people worldwide. Despite decades of study on the neuronal processing of pain, mechanisms underlying enhanced pain states after injury remain unclear. N-methyl-D-aspartate (NMDA) receptor-dependent changes play a critical role in triggering central sensitization in neuropathic pain. These receptors are regulated at the glycine site through a mandatory endogenous co-agonist D-serine, which is synthesized by astrocytes. Therefore, the present study was carried out to determine whether astrocytes are involved, through D-serine secretion, in dynamic mechanical allodynia (DMA) obtained after chronic constriction of the infraorbital nerve (CCI-IoN) in rats. Two weeks after CCI-IoN, an important reaction of astrocytes was present in the medullary dorsal horn (MDH), as revealed by an up-regulation of glial fibrillary acidic protein (GFAP) in allodynic rats. In parallel, an increase in D-serine synthesis, which co-localized with its synthesis enzyme serine racemase, was strictly observed in astrocytes. Blocking astrocyte metabolism by intracisternal delivery of fluorocitrate alleviated DMA. Furthermore, the administration of D-amino-acid oxidase (DAAO), a D-serine-degrading enzyme, or that of L-serine O-sulfate (LSOS), a serine racemase inhibitor, significantly decreased pain behavior in allodynic rats. These results demonstrate that astrocytes are involved in the modulation of orofacial post-traumatic neuropathic pain via the release of the gliotransmitter D-serine.
authors.affiliation: 7280, Neuro-Psycho-pharmacologie des Systèmes Dopaminergiques sous-corticaux, Clermont-Ferrand, Université Clermont1, F-63000, France. wisamdieb@yahoo.com
authors.forename: W
authors.initials: W
authors.lastname: Dieb
authors.forename: A
authors.initials: A
authors.lastname: Hafidi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002946:Cisterna Magna; D002951:Citrates / Q000494:pharmacology; D003251:Constriction, Pathologic / Q000503:physiopathology; D003605:D-Amino-Acid Oxidase / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007267:Injections; D007536:Isomerism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D009915:Orbit / Q000294:innervation; D020671:Posterior Horn Cells / Q000378:metabolism; D019998:Racemases and Epimerases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D014277:Trigeminal Neuralgia / Q000503:physiopathology*; D015854:Up-Regulation; D000099300:Serine Racemase
chemical_list: D002951:Citrates; D003605:D-Amino-Acid Oxidase; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D018377:Neurotransmitter Agents; D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase; C007744:fluorocitrate; C036040:serine O-sulfate
keywords: DAAO; GFAP; fluorocitrate; orofacial pain; serine-racemase