Involvement of the NMDA-Nitric Oxide Pathway in the Development of Hypersensitivity to Tactile Stimulation in Dental Injured Rats

• Published in: Japanese Journal of Pharmacology Vol. 90; no. 2; pp. 145 - 155
• Main Authors: Yonehara, Norifumi, Amano, Katsuhiko, Kamisaki, Yoshinori
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Pharmacological Society 2002
• Subjects: Animals; Behavior, Animal - physiology; Dental injury; Dizocilpine Maleate - pharmacology; Enzyme Inhibitors - pharmacology; Hyperalgesia - etiology; Hyperalgesia - metabolism; Hyperalgesia - physiopathology; Hypersensitivity to tactile stimulation; Immunohistochemistry; Injections, Intraperitoneal; Injections, Intravenous; Male; N-Methylaspartate - metabolism; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type I; NMDA receptor; omega-N-Methylarginine - pharmacology; Pain Measurement; Pain Threshold - drug effects; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - physiology; Tooth Injuries - complications; Touch; Trigeminal Nuclei - metabolism; Trigeminal nucleus caudalis
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.90.145

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 NG-monomethyl-L-arginine monoacetate (L-NMMA: 10 – 100 mg/kg), but not attained by NG-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.