title: IL-1beta in the trigeminal subnucleus caudalis contributes to extra-territorial allodynia/hyperalgesia following a trigeminal nerve injury.
abstract: It has been reported that the whisker pad (WP) area, which is innervated by the second branch of the trigeminal nerve, shows allodynia/hyperalgesia following transection of the mental nerve (MN: the third branch of the trigeminal nerve). However, the mechanisms of this extra-territorial pain induction still remain unclear. Glia and cytokines are known to facilitate perception of noxious input, raising a possibility that these non-neuronal elements are involved in the induction and spread of allodynia/hyperalgesia at non-injured skin territory. One day after MN transection, tactile allodynia/hyperalgesia developed on the ipsilateral WP area, which is in the non-injured skin territory. The tactile allodynia/hyperalgesia lasted for more than 56 days. In response to MN transection, astrocytes and microglia appeared to be in an activated state, and interleukin (IL)-1beta was up-regulated in astrocytes in the trigeminal subnucleus caudalis (Vc). Allodynia/hyperalgesia at WP area induced by MN transection was attenuated dose-dependently by IL-1 receptor antagonist IL-1ra (i.t., 0.05, 0.5, and 5 pg/rat). Fos-like immunoreactive (Fos-Li) neurons were observed in the Vc after non-noxious mechanical stimulation of the WP area in the rats with MN transection. Administration of IL-1ra also attenuated the number of Fos-Li neurons dose-dependently. Administration of a noncompetitive antagonist of NMDA receptors MK-801 (i.t., 5 μg/rat) reversed allodynia/hyperalgesia. IL-1 receptor type I (IL-1RI) was localized in Fos- and phospho NR1-immunoreactive neurons. These results suggest that IL-1beta in the Vc plays an important role in the development of extra-territorial tactile allodynia/hyperalgesia after MN transection.
authors.affiliation: Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Science, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Takahashi
authors.forename: Mineo
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yohei
authors.initials: Y
authors.lastname: Suekawa
authors.forename: Goshi
authors.initials: G
authors.lastname: Ito
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Inubushi
authors.forename: Naoto
authors.initials: N
authors.lastname: Hirose
authors.forename: Kyoko
authors.initials: K
authors.lastname: Murasaki
authors.forename: Shinji
authors.initials: S
authors.lastname: Hiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Uchida
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tanne
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007278:Injections, Spinal; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism*; D008334:Mandible / Q000294:innervation; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D014275:Trigeminal Caudal Nucleus / Q000378:metabolism* / Q000473:pathology; D061221:Trigeminal Nerve Injuries; D015854:Up-Regulation / Q000502:physiology; D014738:Vibrissae / Q000294:innervation
chemical_list: D018501:Antirheumatic Agents; D018691:Excitatory Amino Acid Antagonists; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D016291:Dizocilpine Maleate