P2X₃ and TRPV1 functionally interact and mediate sensitization of trigeminal sensory neurons.
P2X₃ and TRPV1 functionally interact and mediate sensitization of trigeminal sensory neurons.
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DOI：
10.1016/j.neuroscience.2012.11.015
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发表时间：
2013-03-01
期刊：
影响因子：
3.3
通讯作者：
Ro, J. Y.
中科院分区：
文献类型：
--
作者：
Saloman, J. L.;Chung, M. -K.;Ro, J. Y.
肌肉骨骼疼痛状况，特别是与颞下颌关节和肌肉疾病（TMD）相关的那些，影响大部分人口。识别潜在的痛觉过敏机制可能有助于开发新的治疗策略，用于管理TMD和其他肌肉疼痛状况。在这项研究中，我们提供了证据的两个配体门控通道，P2 X3和TRPV 1，在三叉神经感觉神经元之间的功能相互作用，并提出这种相互作用作为一个潜在的机制，机械痛觉过敏的发展。在轻度麻醉大鼠中，通过电子麻醉计评估咬肌的机械敏感性。直接肌肉注射选择性P2 X3激动剂αβmeATP可诱导剂量和时间依赖性痛觉过敏。对侧肌肉的机械敏感性不受影响，表明局部P2 X3介导痛觉过敏。麻醉覆盖的皮肤对αβ meATP诱导的痛觉过敏没有影响，证实了来自肌肉的P2 X3的贡献。重要的是，用TRPV 1拮抗剂AMG 9810预处理肌肉可预防αβ meATP诱导的痛觉过敏。P2 X3与TRPV 1在咬肌传入中共表达，证实了细胞内相互作用的可能性。此外，在P2 X3/TRPV 1阳性神经元的亚群中，辣椒素诱导的Ca 2+瞬变在P2 X3激活后显著放大。最后，激活P2 X3诱导磷酸化的丝氨酸，但不是苏氨酸，在TRPV 1在三叉神经节培养物中的残基。在15分钟时观察到显著的磷酸化，在该时间点，行为痛觉过敏是突出的。以前，P2 X3或TRPV 1的激活独立地涉及机械性痛觉过敏的发展。我们的数据表明P2 X3和TRPV 1以易化的方式相互作用，这可能有助于已知的咬肌痛觉过敏的基础外周敏化。
Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) affect a large percentage of the population. Identifying mechanisms underlying hyperalgesia could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. In this study, we provide evidence of functional interactions between two ligand-gated channels, P2X3 and TRPV1, in trigeminal sensory neurons, and propose that the interactions serve as an underlying mechanism for the development of mechanical hyperalgesia. Mechanical sensitivity of the masseter muscle was assessed in lightly anesthetized rats via an electronic anesthesiometer. Direct intramuscular injection of a selective P2X3 agonist, αβmeATP, induced a dose- and time-dependent hyperalgesia. Mechanical sensitivity in the contralateral muscle was unaffected suggesting local P2X3 mediate the hyperalgesia. Anesthetizing the overlying skin had no effect on αβmeATP-induced hyperalgesia confirming the contribution of P2X3 from muscle. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810. P2X3 was co-expressed with TRPV1 in masseter muscle afferents confirming the possibility for intracellular interactions. Additionally, in a subpopulation of P2X3/TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly amplified following P2X3 activation. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal ganglia cultures. Significant phosphorylation was observed at 15 min, the time point at which behavioral hyperalgesia was prominent. Previously, activation of either P2X3 or TRPV1 had been independently implicated in the development of mechanical hyperalgesia. Our data propose P2X3 and TRPV1 interact in a facilitatory manner, which could contribute to the peripheral sensitization known to underlie masseter hyperalgesia.
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影响因子：
3.3
作者：
CHOLEWINSKI, A;BURGESS, GM;BEVAN, S
通讯作者：
BEVAN, S
影响因子：
7.4
作者：
Ambalavanar, R;Moritani, M;Dessem, D
通讯作者：
Dessem, D
影响因子：
3.4
作者：
Guo, A;Vulchanova, L;Elde, R
通讯作者：
Elde, R
影响因子：
2.9
作者：
HARNESS, DM;DONLON, WC;EVERSOLE, LR
通讯作者：
EVERSOLE, LR
DOI：
10.1124/jpet.105.083915
发表时间：
2005-07-01
影响因子：
3.5
作者：
Honore, P;Wismer, CT;Jarvis, MF
通讯作者：
Jarvis, MF