Involvement of the NMDA-nitric oxide pathway in the development of hypersensitivity to tactile stimulation in dental injured rats.
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.
Yonehara
Norifumi
N
Department of Pharmacology, Osaka University Graduate School of Dentistry, Osaka, Japan. yonehara@dent.saka-u.ac.jp
Amano
Katsuhiko
K
Kamisaki
Yoshinori
Y
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
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