title: P2X7 receptor and cytokines contribute to extra-territorial facial pain.
abstract: The whisker pad area (WP) is innervated by the second branch of the trigeminal nerve and experiences allodynia and hyperalgesia following transection of the mental nerve (MN; the third branch of the trigeminal nerve). However, the mechanisms of this extra-territorial pain remain unclear. The ionotropic P2X(7) ATP receptor (P2X(7)) in microglia is known to potentiate, via cytokines, the perception of noxious stimuli, raising the possibility that P2X(7) and cytokines are involved in this extra-territorial pain. One day after MN transection (MNT), WP allodynia/hyperalgesia developed, which lasted for > 8 wks. Activation of microglia and up-regulation of P2X(7), membrane-bound tumor necrosis factor (TNF)-α (mTNF-α), and soluble TNF-α (sTNF-α) in the trigeminal sensory nuclear complex (TNC) were evident for up to 6 wks after MNT. Allodynia/hyperalgesia after MNT was blocked by intracisternal administration of etanercept, a recombinant TNF-α receptor (p75)-Fc fusion protein. Intracisternal A438079, a P2X(7) antagonist, also attenuated allodynia/hyperalgesia and blocked up-regulation of mTNF-α and sTNF-α in the TNC. We conclude that sTNF-α released by microglia following P2X(7) activation may be important in both the initiation and maintenance of extra-territorial pain after MNT.
authors: Department of Orthodontics, Applied Life Sciences, Hiroshima University Institute of Biomedical & Health Sciences, Minami-ku, Hiroshima, Japan.
authors: K
authors: K
authors: Murasaki
authors: M
authors: M
authors: Watanabe
authors: K
authors: K
authors: Takahashi
authors: G
authors: G
authors: Ito
authors: Y
authors: Y
authors: Suekawa
authors: T
authors: T
authors: Inubushi
authors: N
authors: N
authors: Hirose
authors: T
authors: T
authors: Uchida
authors: K
authors: K
authors: Tanne
mesh_terms: D000818:Animals; D059350:Chronic Pain / Q000378:metabolism; D005157:Facial Pain / Q000503:physiopathology*; D006930:Hyperalgesia / Q000378:metabolism*; D008297:Male; D008340:Mandibular Nerve / Q000601:surgery; D017628:Microglia / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000502:physiology*; D014275:Trigeminal Caudal Nucleus / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000502:physiology; D014738:Vibrissae / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D058486:Receptors, Purinergic P2X7; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases