title: Nerve growth factor contribution via transient receptor potential vanilloid 1 to ectopic orofacial pain.
abstract: It is well known that oral inflammation causes tenderness in temporomandibular joints or masseter muscles. The exact mechanism of such an orofacial ectopic hyperalgesia remains unclear. Here, we investigated the functional significance of interaction of nerve growth factor (NGF) and transient receptor potential vanilloid 1 (TRPV1) in relation to heat hyperalgesia in the whisker pad skin caused by complete Freund's adjuvant (CFA) injection into the lower lip. CFA injection induced heat hyperalgesia of the ipsilateral whisker pad skin. Moreover, it leads to enhancement of spontaneous activity and heat responses in trigeminal ganglion (TG) neurons that was elicited by heat stimulation of the whisker pad skin. The heat hyperalgesia was dose-dependently reversed by intraperitoneal TRPV1 antagonist administration, also diminished by neutralizing anti-NGF antibody administration into the lower lip and intraganglionic administration of K252a, a tyrosine kinase receptor inhibitor. Nerve fibers in bundle of mandibular nerve and TG neurons that innervates the whisker pad skin and lower lip both expressed labeled NGF, which was administrated into the lower lip. Moreover, the NGF concentrations in ophthalmic-maxillary and mandibular divisions of the TG increased after CFA injection into the lower lip. The number of TRPV1-positive neurons that innervates the whisker pad skin and lower lip was increased after CFA injection into the lower lip, and this increase was annulled by anti-NGF administration. The present findings suggest that inflammation in the lower lip induces release of NGF that regulates TRPV1 expression in TG neurons. This TRPV1 overexpression may underlie ectopic heat hyperalgesia in the whisker pad skin.
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Tokyo 101-8310, Japan. shinoda-m@dent.nihon-u.ac.jp
authors.forename: Masamichi
authors.initials: M
authors.lastname: Shinoda
authors.forename: Masatake
authors.initials: M
authors.lastname: Asano
authors.forename: Daisuke
authors.initials: D
authors.lastname: Omagari
authors.forename: Kuniya
authors.initials: K
authors.lastname: Honda
authors.forename: Suzuro
authors.initials: S
authors.lastname: Hitomi
authors.forename: Ayano
authors.initials: A
authors.lastname: Katagiri
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D057134:Antibodies, Neutralizing; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002227:Carbazoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005157:Facial Pain / Q000378:metabolism* / Q000503:physiopathology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology; D026121:Indole Alkaloids / Q000494:pharmacology; D008297:Male; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050916:TRPV Cation Channels / Q000378:metabolism*; D014738:Vibrissae
chemical_list: D057134:Antibodies, Neutralizing; D002227:Carbazoles; D026121:Indole Alkaloids; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D020932:Nerve Growth Factor; C049985:staurosporine aglycone