Astrocytes are Involved in Trigeminal Dynamic Mechanical Allodynia: Potential Role of D-serine

• Published in: Journal of dental research 2013-09, Vol.92 (9), p.808-813
• Main Authors: Dieb, W., Hafidi, A.
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes - drug effects; Astrocytes - metabolism; Cisterna Magna; Citrates - pharmacology; Constriction, Pathologic - physiopathology; D-Amino-Acid Oxidase - pharmacology; Dentistry; Glial Fibrillary Acidic Protein - metabolism; Injections; Isomerism; Male; Membrane Proteins - metabolism; Neurotransmitter Agents - metabolism; Orbit - innervation; Posterior Horn Cells - metabolism; Racemases and Epimerases - antagonists & inhibitors; Racemases and Epimerases - metabolism; Rats; Rats, Sprague-Dawley; Serine - analogs & derivatives; Serine - antagonists & inhibitors; Serine - metabolism; Serine - pharmacology; Trigeminal Neuralgia - physiopathology; Up-Regulation
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/0022034513498898

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.