title: Involvement of the NMDA-nitric oxide pathway in the development of hypersensitivity to tactile stimulation in dental injured rats.
abstract: To investigate mechanisms in pathological pain conditions as the hyperalgesia and allodynia observed after dental surgery, we employed a rat dental-injury model involving the simultaneous pulpectomy to a lower incisor and extraction of an ipsilateral upper incisor. We found that hypersensitivity to tactile stimulation developed on both ipsilateral and contralateral sides in the dental-injured rats 5 days after the surgery and that this lasted for at least 30 days. Recovery from hypersensitivity to tactile stimulation was achieved by the intraperitoneal (i.p.) administration of MK-801 (0.05 mg/kg) or N(G)-monomethyl-L-arginine monoacetate (L-NMMA: 10 - 100 mg/kg), but not attained by N(G)-monomethyl-D-arginine monoacetate (D-NMMA: 100 mg/kg). This recovery effect of L-NMMA (50 mg/kg) was inhibited by pretreatment with L-arginine (600 mg/kg). In the trigeminal nucleus caudalis (SpVc), the changes in nitric oxide (NO) levels invoked by the intravenous (i.v.) administration of N-methyl-D-aspartate (NMDA; 10 mg/kg) were found to be significantly larger in the dental-injured rats than in sham-operated rats. The number of neuronal NO synthase (nNOS)-positive neurons increased in layers I-II and III-IV in the SpVc on both sides of the dental-injured rats. These results suggest that hypersensitivity to tactile stimulation developed following dental injury, and that NMDA receptor/NOS/NO production pathways in the SpVc may be involved in pathological conditions.
authors.affiliation: Department of Pharmacology, Osaka University Graduate School of Dentistry, Osaka, Japan. yonehara@dent.saka-u.ac.jp
authors.forename: Norifumi
authors.initials: N
authors.lastname: Yonehara
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Amano
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kamisaki
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D018677:Tooth Injuries / Q000150:complications*; D014110:Touch; D014278:Trigeminal Nuclei / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat