Central sensitization of nociceptive neurons in rat medullary dorsal horn involves purinergic P2X7 receptors.
Central sensitization of nociceptive neurons in rat medullary dorsal horn involves purinergic P2X7 receptors.
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DOI：
10.1016/j.neuroscience.2011.06.083
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发表时间：
2011-09-29
期刊：
影响因子：
3.3
通讯作者：
Sessle, B. J.
中科院分区：
文献类型：
--
作者：
Itoh, K.;Chiang, C. -Y.;Li, Z.;Lee, J. -C.;Dostrovsky, J. O.;Sessle, B. J.
中枢致敏是外周组织损伤和炎症后伤害性通路神经元兴奋性增加的关键过程。我们以前的研究结果表明，细胞外ATP分子作用于位于突触前末梢的嘌呤能受体（例如，P2 X2/3，P2 X3亚基）和神经胶质细胞参与了在髓背角（MDH）伤害感受神经元中通过将炎性刺激物芥子油（MO）应用于牙髓而诱导的突触依赖性中枢敏化。由于越来越多的证据表明，位于神经胶质细胞上的P2 X7受体的激活参与慢性炎症性和神经性疼痛，本研究的目的是在体内测试P2 X7受体参与这种急性炎症性疼痛模型。实验在麻醉的Sprague-Dawley雄性大鼠中进行。在MDH功能鉴定的伤害性神经元上进行单单位记录，测试其机械感受野、机械激活阈值和对伤害性刺激的反应。我们发现，连续鞘内（i.t.）在MDH上灌注有效的P2 X7受体拮抗剂亮蓝G和高碘酸氧化ATP可以各自显著减弱MO诱导的MDH中枢敏化。MDH中枢致敏也可通过i.t.灌注ATP，甚至更有效地通过P2 X7受体激动剂苯甲酰苯甲酰基ATP。灌流的小胶质细胞阻滞剂米诺环素废除了MO诱导的MDH中枢敏化，与背角P2 X7受体主要在小胶质细胞上表达的报道一致。在对照实验中，在MDH上灌注溶媒未产生任何显著变化。这些新的发现表明，体内P2 X7受体的激活可能参与急性炎性疼痛模型中中枢致敏的发展。
Central sensitization is a crucial process underlying the increased neuronal excitability of nociceptive pathways following peripheral tissue injury and inflammation. Our previous findings have suggested that extracellular ATP molecules acting at purinergic receptors located on presynaptic terminals (e.g., P2X2/3, P2X3 subunits) and glial cells are involved in the glutamatergic-dependent central sensitization induced in medullary dorsal horn (MDH) nociceptive neurons by application to the tooth pulp of the inflammatory irritant mustard oil (MO). Since growing evidence indicates that activation of P2X7 receptors located on glia is involved in chronic inflammatory and neuropathic pain, the aim of the present study was to test in vivo for P2X7 receptor involvement in this acute inflammatory pain model. Experiments were carried out in anesthetized Sprague-Dawley male rats. Single unit recordings were made in MDH functionally identified nociceptive neurons for which mechanoreceptive field, mechanical activation threshold and responses to noxious stimuli were tested. We found that continuous intrathecal (i.t.) superfusion over MDH of the potent P2X7 receptor antagonists brilliant blue G and periodated oxidized ATP could each significantly attenuate the MO-induced MDH central sensitization. MDH central sensitization could also be produced by i.t. superfusion of ATP and even more effectively by the P2X7 receptor agonist benzoylbenzoyl ATP. Superfusion of the microglial blocker minocycline abolished the MO-induced MDH central sensitization, consistent with reports that dorsal horn P2X7 receptors are mostly expressed on microglia. In control experiments, superfusion over MDH of vehicle did not produce any significant changes. These novel findings suggest that activation of P2X7 receptors in vivo may be involved in the development of central sensitization in an acute inflammatory pain model.
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DOI：
10.1523/jneurosci.3295-09.2010
发表时间：
2010-01-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Clark AK;Staniland AA;Marchand F;Kaan TK;McMahon SB;Malcangio M
通讯作者：
Malcangio M
影响因子：
7.3
作者：
Beigi, RD;Kertesy, SB;Dubyak, GR
通讯作者：
Dubyak, GR
小胶质细胞 P2X7 受体和下游信号通路参与脊髓伤害性反应的长期增强
影响因子：
15.1
作者：
Chu, Yu-Xia;Zhang, Yan;Zhao, Zhi-Qi
通讯作者：
Zhao, Zhi-Qi
影响因子：
7.3
作者：
Donnelly-Roberts, Diana L.;Namovic, Marian T.;Jarvis, Michael F.
通讯作者：
Jarvis, Michael F.
DOI：
10.1177/039463200802100108
发表时间：
2008-01-01
影响因子：
3.5
作者：
Fulgenzi, A.;Ticozzi, P.;Ferrero, M. E.
通讯作者：
Ferrero, M. E.