title: Nitric oxide signaling contributes to ectopic orofacial neuropathic pain.
abstract: Inferior alveolar nerve (IAN) injury induces persistent ectopic pain which spreads to a wide area in the orofacial region. Its exact mechanism remains unclear. We investigated the involvement of nitric oxide (NO) in relation to ectopic orofacial pain caused by IAN transection (IANX). We assessed the changes in mechanical sensitivity of the whisker pad skin following IANX, neuronal nitric oxide synthase (nNOS) expression in the trigeminal ganglion (TG), and the functional significance of NO in relation to the mechanical allodynia following intra-TG administration of a chemical precursor to NO and selective nNOS inhibitors. IANX induced mechanical allodynia, which was diminished by intra-TG administration of selective nNOS inhibitors. NO metabolites and nNOS immunoreactive neurons innervating the lower lip were also increased in the TG. Intra-TG administration of nNOS substrate induced the mechanical allodynia. The present findings suggest that NO released from TG neurons regulates the excitability of TG neurons innervating the whisker pad skin, and the enhancement of TG neuronal excitability may underlie ectopic mechanical allodynia.
authors.affiliation: Department of Oral Histology, Kanagawa Dental College, 82 Inaoka-cho, Yokosuka, 238-8580, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sugiyama
authors.forename: M
authors.initials: M
authors.lastname: Shinoda
authors.forename: T
authors.initials: T
authors.lastname: Watase
authors.forename: K
authors.initials: K
authors.lastname: Honda
authors.forename: R
authors.initials: R
authors.lastname: Ito
authors.forename: K
authors.initials: K
authors.lastname: Kaji
authors.forename: K
authors.initials: K
authors.lastname: Urata
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: K
authors.initials: K
authors.lastname: Ohara
authors.forename: O
authors.initials: O
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Echizenya
authors.forename: K
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000494:pharmacology; D005157:Facial Pain / Q000209:etiology*; D006930:Hyperalgesia / Q000209:etiology; D007191:Indazoles / Q000494:pharmacology; D008046:Lip / Q000294:innervation; D008297:Male; D008340:Mandibular Nerve / Q000473:pathology / Q000503:physiopathology*; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D009437:Neuralgia / Q000209:etiology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009569:Nitric Oxide / Q000032:analysis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I / Q000032:analysis / Q000037:antagonists & inhibitors; D017288:Pain Threshold / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012684:Sensory Thresholds / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014110:Touch / Q000502:physiology; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000473:pathology; D061221:Trigeminal Nerve Injuries / Q000150:complications*
chemical_list: D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D007191:Indazoles; C109599:N(omega)-propylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C080122:7-nitroindazole
keywords: 7-nitroindazole; L-arginine; infraorbital nerve injury; mechanical allodynia; nitric oxide synthase; trigeminal ganglion