Department of Orthodontics, Applied Life Sciences, Hiroshima University Institute of Biomedical & Health Sciences, Minami-ku, Hiroshima, Japan.
J Dent Res. 2013 Mar;92(3):260-5. doi: 10.1177/0022034512474668. Epub 2013 Jan 22.
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.
触须垫区域（WP）由三叉神经的第二分支支配，在切断下颌神经（MN；三叉神经的第三分支）后会经历异常性疼痛和痛觉过敏。然而，这种跨区域疼痛的机制尚不清楚。已知小胶质细胞中的离子型 P2X（7）ATP 受体（P2X（7））通过细胞因子增强对有害刺激的感知，这增加了 P2X（7）和细胞因子参与这种跨区域疼痛的可能性。在 MN 切断后 1 天（MNT），WP 出现异常性疼痛/痛觉过敏，持续时间超过 8 周。MNT 后长达 6 周，三叉神经感觉核复合体（TNC）中小胶质细胞的激活和 P2X（7）、膜结合肿瘤坏死因子（TNF）-α（mTNF-α）和可溶性 TNF-α（sTNF-α）的上调是明显的。MNT 后异常性疼痛/痛觉过敏可被鞘内给予依那西普（一种重组 TNF-α受体（p75）-Fc 融合蛋白）阻断。鞘内给予 A438079（一种 P2X（7）拮抗剂）也可减轻异常性疼痛/痛觉过敏，并阻断 TNC 中 mTNF-α和 sTNF-α的上调。我们得出结论，P2X（7）激活后小胶质细胞释放的 sTNF-α可能在 MNT 后跨区域疼痛的起始和维持中都很重要。
