Central Terminal Sensitization of TRPV1 by Descending Serotonergic Facilitation Modulates Chronic Pain

详细信息    查看全文

• 作者：Yu聽Shin Kim ; Yuxia Chu ; Liang Han ; Man Li ; Zhe Li ; Pamela聽Colleen LaVinka ; Shuohao Sun ; Zongxiang Tang ; Kyoungsook Park ; Michael聽J. Caterina ; Ke Ren ; Ronald Dubner ; Feng Wei ; Xinzhong Dong
• 刊名：Neuron
• 出版年：19 February, 2014
• 年：2014
• 卷：81
• 期：4
• 页码：873-887
• 全文大小：4897 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

The peripheral terminals of primary nociceptive neurons play an essential role in pain detection mediated聽by membrane receptors like TRPV1, a molecular sensor of heat and capsaicin. However, the contribution of central terminal TRPV1 in the dorsal horn聽to chronic pain has not been investigated directly. Combining primary sensory neuron-specific GCaMP3 imaging with a trigeminal neuropathic pain model, we detected robust neuronal hyperactivity in injured and uninjured nerves in the skin, soma in trigeminal ganglion, and central terminals in the spinal trigeminal nucleus. Extensive TRPV1 hyperactivity was observed in central terminals innervating all dorsal horn laminae. The central terminal TRPV1 sensitization was maintained by descending serotonergic (5-HT) input from the brainstem. Central blockade of TRPV1 or 5-HT/5-HT3A receptors attenuated central terminal sensitization, excitatory primary afferent inputs, and mechanical hyperalgesia in the territories of injured and uninjured nerves. Our results reveal central mechanisms facilitating central terminal sensitization underlying chronic pain.