title: Organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis and upper cervical spinal cord associated with orofacial neuropathic pain.
abstract: The aim of this study was to evaluate spatial organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1), and to clarify the involvement in mechanisms underlying orofacial secondary hyperalgesia following infraorbital nerve injury. We found that the head-withdrawal threshold to non-noxious mechanical stimulation of the maxillary whisker pad skin was significantly reduced in chronic constriction injury of the infraorbital nerve (ION-CCI) rats from day 1 to day 14 after ION-CCI. On day 3 after ION-CCI, mechanical allodynia was obvious in the orofacial skin areas innervated by the 1st and 3rd branches of the trigeminal nerve as well as the 2nd branch area. Hyperactive microglial cells in Vc and C1 were observed on days 3 and 7 after ION-CCI. On day 3 after ION-CCI, a large number of phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) cells were observed in Vc and C1. Many hyperactive microglial cells were also distributed over a wide area of Vc and C1 innervated by the trigeminal nerve. The intraperitoneal administration of minocycline significantly reduced the activation of microglial cells and the number of pERK-IR cells in Vc and C1, and also significantly attenuated the development of mechanical allodynia. Furthermore, enhanced background activity and mechanical evoked responses of Vc wide dynamic range neurons in ION-CCI rats were significantly reversed following minocycline administration. These findings suggest that activation of microglial cells over a wide area of Vc and C1 is involved in the enhancement of Vc and C1 neuronal excitability in the early period after ION-CCI, resulting in the neuropathic pain in orofacial areas innervated by the injured as well as uninjured nerves.
authors.affiliation: Department of Orthodontics, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shibuta
authors.forename: Ikuko
authors.initials: I
authors.lastname: Suzuki
authors.forename: Masamichi
authors.initials: M
authors.lastname: Shinoda
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tsuboi
authors.forename: Kuniya
authors.initials: K
authors.lastname: Honda
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Sessle
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000818:Animals; D002574:Cervical Vertebrae; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005157:Facial Pain / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D014275:Trigeminal Caudal Nucleus / Q000378:metabolism*
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases