title: Regulation of the trigeminal NR1 subunit expression induced by inflammation of the temporomandibular joint region in rats.
abstract: Expression of the N-methyl-d-aspartate (NMDA) receptor in trigeminal nuclei has been shown to play a role in the mechanisms of trigeminal pain. Here, we examined the hypothesis that the upregulation of the NR1 subunit of the NMDA receptor (NR1) in the trigeminal subnucleus caudalis (Sp5c) following inflammation of the temporomandibular joint (TMJ) region would be regulated by interleukin-6 (IL-6) and the nuclear factor-kappa B (NF-kappaB). Inflammation of a unilateral TMJ region was produced in rats by injecting 50mul of complete Freund's adjuvant (CFA) into a TMJ and adjacent tissues, which resulted in persistent pain behavior as assessed using algometer before (baseline) and on days 1, 3, and 7 after the CFA injection. The CFA injection also induced a significant upregulation of NR1 and NF-kappaB on days 3 and 7, and of IL-6 on days 1, 3, and 7, within the ipsilateral Sp5c, as compared with the sham TMJ injection group. Once daily intracisternal injection of an IL-6 antiserum or NF-kappaB inhibitor (PDTC) for 6 days, beginning on day 1 immediately after the CFA injection, prevented both the upregulation of NR1 in the ipsilateral Sp5C and pain behavior. Moreover, once daily intracisternal IL-6 administration for 6 days in naïve rats induced the NR1 upregulation and pain behavior similar to that after TMJ inflammation. These results indicate that the upregulation of IL-6 and NF-kappaB after inflammation of the unilateral TMJ region is a critical regulatory mechanism for the expression of NR1 in the ipsilateral Sp5c, which contributed to the development of TMJ pain behavior in rats.
authors.affiliation: MGH Center for Translational Pain Research, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, WACC 324, Boston, MA 02114, USA.
authors.forename: Shuxing
authors.initials: S
authors.lastname: Wang
authors.forename: Grewo
authors.initials: G
authors.lastname: Lim
authors.forename: Ji
authors.initials: J
authors.lastname: Mao
authors.forename: Backil
authors.initials: B
authors.lastname: Sung
authors.forename: Jianren
authors.initials: J
authors.lastname: Mao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000009:adverse effects; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013704:Temporomandibular Joint / Q000378:metabolism*; D013705:Temporomandibular Joint Disorders / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D013859:Thiocarbamates / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D000906:Antibodies; D000975:Antioxidants; D005620:Freund's Adjuvant; D015850:Interleukin-6; D011392:Proline; D017346:Protein Serine-Threonine Kinases; D016194:Receptors, N-Methyl-D-Aspartate; D013859:Thiocarbamates; D000097782:NF-kappaB-Inducing Kinase; C409466:NR1 NMDA receptor; C066229:prolinedithiocarbamate