Early afferent activity from the facet joint after painful trauma to its capsule potentiates neuronal excitability and glutamate signaling in the spinal cord.
Early afferent activity from the facet joint after painful trauma to its capsule potentiates neuronal excitability and glutamate signaling in the spinal cord.
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DOI：
10.1016/j.pain.2014.06.019
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发表时间：
2014-09
期刊：
影响因子：
7.4
通讯作者：
Winkelstein BA
中科院分区：
文献类型：
--
作者：
Crosby ND;Gilliland TM;Winkelstein BA
颈椎小关节损伤引起持续性疼痛和中枢敏感化。阻止引发敏化的外周神经元信号减弱神经性疼痛。然而，小关节传入活动、中枢致敏的发展和疼痛之间没有明确的关系，这可能阻碍了对这种疼痛综合征的有效治疗。本研究探讨了如何传入活动从受伤的颈椎小关节影响诱导的行为敏感性和中枢敏感化。关节内注射布比卡因，以暂时抑制传入活动立即或4天后，小关节损伤。在损伤后监测机械性痛觉过敏，并在第7天测量脊髓神经元过度兴奋性和促进神经元兴奋性的蛋白质的脊髓表达。用盐水载体处理的小关节损伤诱导显著的机械性痛觉过敏（p<0.027）、背角神经元过度兴奋（p<0.026）、pERK 1/2、pNR 1、mGluR 5、GLAST和GFAP的上调以及GLT 1的下调（p<0.032）。然而，在损伤后立即关节内注射布比卡因可显著减轻痛觉过敏（p<0.0001）、神经元过度兴奋（p<0.004）和兴奋性信号蛋白的失调（p<0.049）。相比之下，第4天关节内注射布比卡因对这些结果没有影响。在神经元过度兴奋的发展过程中（4小时、8小时、1天）沉默传入活动仅在损伤后4小时给予治疗时减弱痛觉过敏和神经元过度兴奋（p<0.045）。这项研究表明，早期传入活动，从受伤的小关节诱导脊髓敏化通过脊髓兴奋性神经递质信号。外周干预阻断传入活动仅在损伤后早期和脊髓改变发生之前的短时间内有效，并且不依赖于调节脊髓胶质细胞活化。
Cervical facet joint injury induces persistent pain and central sensitization. Preventing the peripheral neuronal signals that initiate sensitization attenuates neuropathic pain. Yet, there is no clear relationship between facet joint afferent activity, development of central sensitization, and pain, which may be hindering effective treatments for this pain syndrome. This study investigates how afferent activity from the injured cervical facet joint affects induction of behavioral sensitivity and central sensitization. Intra-articular bupivacaine was administered to transiently suppress afferent activity immediately or 4 days after facet injury. Mechanical hyperalgesia was monitored after injury, and spinal neuronal hyperexcitability and spinal expression of proteins that promote neuronal excitability were measured on day 7. Facet injury with saline vehicle treatment induced significant mechanical hyperalgesia (p<0.027), dorsal horn neuronal hyperexcitability (p<0.026), upregulation of pERK1/2, pNR1, mGluR5, GLAST, and GFAP, and downregulation of GLT1 (p<0.032). However, intra-articular bupivacaine immediately after injury significantly attenuated hyperalgesia (p<0.0001), neuronal hyperexcitability (p<0.004), and dysregulation of excitatory signaling proteins (p<0.049). In contrast, intra-articular bupivacaine at day 4 had no effect on these outcomes. Silencing afferent activity during the development of neuronal hyperexcitability (4hr, 8hr, 1 day) attenuated hyperalgesia and neuronal hyperexcitability (p<0.045) only for the treatment given 4 hours after injury. This study suggests that early afferent activity from the injured facet induces development of spinal sensitization via spinal excitatory glutamatergic signaling. Peripheral intervention blocking afferent activity is only effective over a short period of time early after injury and before spinal modifications develop, and is independent of modulating spinal glial activation.
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