title: Role of NMDA receptors in the trigeminal pathway, and the modulatory effect of magnesium in a model of rat temporomandibular joint arthritis.
abstract: Temporomandibular joint (TMJ) arthritis is a common cause of orofacial pain. In the present study, the modulatory effects of N-methyl-d-aspartate receptors (NMDA-Rs) and magnesium were investigated in TMJ arthritis hypernociception. Male Wistar rats received an intra-articular injection of carrageenan (Cg) in the TMJ, and mechanical hypernociception was measured. The NMDA-R antagonist, MK-801, and magnesium chloride (MgCl₂ ) were administered before arthritis induction. Magnesium deficiency was promoted by feeding rats a synthetic magnesium-free diet for 9 d before injection of Cg. The Cg induced mechanical hypernociception that lasted for 120 h. MK-801 inhibited this hypernociceptive state. MgCl₂ pretreatment prevented Cg-induced hypernociception and altered the nociceptive threshold in the absence of Cg. Magnesium deficiency increased hypernociception and induced spontaneous hypernociceptive behavior. TMJ arthritis increased the expression of mRNA for all NMDA-R subunits and immunostaining of phosphorylated NR1 (phospho-NR1). MgCl₂ inhibited expression of NR2B mRNA and phospho-NR1 immunostaining and increased expression of NR3 mRNA. Magnesium deficiency increased expression of both NR1 and NR3 mRNAs and phospho-NR1 immunostaining in the trigeminal subnucleus caudalis. We found that magnesium modulates nociceptive behavior and induces NMDA-R subunit rearrangement in the subnucleus caudalis. The present results may lead to a better understanding of central processing in the nociceptive trigeminal pathway and the development of new approaches to treat orofacial pain with a TMJ origin.
authors.affiliation: Medical Sciences Post-Graduation Program, Department of Clinical Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: André L C
authors.initials: AL
authors.lastname: Cavalcante
authors.forename: Rafaelly M P
authors.initials: RM
authors.lastname: Siqueira
authors.forename: Joana C B
authors.initials: JC
authors.lastname: Araujo
authors.forename: Delane V
authors.initials: DV
authors.lastname: Gondim
authors.forename: Ronaldo A
authors.initials: RA
authors.lastname: Ribeiro
authors.forename: Josiane S
authors.initials: JS
authors.lastname: Quetz
authors.forename: Alexandre
authors.initials: A
authors.lastname: Havt
authors.forename: Aldo A M
authors.initials: AA
authors.lastname: Lima
authors.forename: Mariana L
authors.initials: ML
authors.lastname: Vale
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002351:Carrageenan; D015870:Gene Expression; D008274:Magnesium / Q000097:blood / Q000494:pharmacology*; D008275:Magnesium Deficiency / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D059226:Nociceptive Pain / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013705:Temporomandibular Joint Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D013997:Time Factors; D014275:Trigeminal Caudal Nucleus / Q000378:metabolism*; D014276:Trigeminal Nerve / Q000187:drug effects* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D002351:Carrageenan; D008274:Magnesium
keywords: N-methyl-d-aspartate receptor (NMDA-R); NR3; magnesium; orofacial pain; temporomandibular joint