title: P2X3 receptor mediates ectopic mechanical allodynia with inflamed lower lip in mice.
abstract: Ectopic pain in other orofacial regions develops with local inflammation in separated orofacial structures. However, the basis for the spreading of pain to adjacent orofacial areas after local inflammation is still unknown. In the present study, we determined if the P2X(3) receptor (P2X(3)R) was associated with altered mechanical sensitivity of the whisker pad skin following complete Freund's adjuvant (CFA) injection into the lower lip. Mice with local inflammation induced by CFA injection into the lower lip demonstrated significant mechanical allodynia of whisker pad skin. The mechanical allodynia was reversed by P2X(3)R antagonist, A-317491 administration into whisker pad skin. The number of P2X(3)R and calcitonin gene-related peptide (CGRP) positive trigeminal ganglion (TG) neurons that innervates the whisker pad skin and lower lip was increased after CFA injection into the lower lip. CGRP protein expression in TG ipsilateral to CFA injection was also significantly greater than that of the saline-injected mice. The present findings suggest that induced CGRP by local inflammation in the lower lip increases P2X(3)R in TG neurons, the increased P2X(3)Rs are involved in the sensitization of primary afferent neurons in the whisker pad skin. This P2X(3)R overexpression may underlie ectopic mechanical allodynia in the whisker pad skin after CFA injection into the lower lip.
authors.affiliation: Division of Pediatric Dentistry, Department of Craniofacial Growth and Development Dentistry, Kanagawa Dental College, Kanagawa, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yasuda
authors.forename: Masamichi
authors.initials: M
authors.lastname: Shinoda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kiyomoto
authors.forename: Kuniya
authors.initials: K
authors.lastname: Honda
authors.forename: Azumi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Takaaki
authors.initials: T
authors.lastname: Tamagawa
authors.forename: Kaori
authors.initials: K
authors.lastname: Kaji
authors.forename: Shigenari
authors.initials: S
authors.lastname: Kimoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002613:Cheilitis / Q000139:chemically induced / Q000378:metabolism*; D005620:Freund's Adjuvant / Q000633:toxicity; D006930:Hyperalgesia / Q000378:metabolism*; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008046:Lip; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053591:Referred Pain / Q000139:chemically induced / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism*; D012867:Skin / Q000294:innervation; D014738:Vibrissae / Q000294:innervation
chemical_list: D058477:Receptors, Purinergic P2X3; D005620:Freund's Adjuvant; D015740:Calcitonin Gene-Related Peptide