The thalamocortical(TC)circuit is closely asso-ciated with pain processing.The hyperpolarization-activated cyclic nucleotide-gated(HCN)2 channel is predominantly expressed in the ventral posterolateral thalamus(VPL)th...The thalamocortical(TC)circuit is closely asso-ciated with pain processing.The hyperpolarization-activated cyclic nucleotide-gated(HCN)2 channel is predominantly expressed in the ventral posterolateral thalamus(VPL)that has been shown to mediate neuropathic pain.However,the role of VPL HCN2 in modulating TC circuit activity is largely unknown.Here,by using optogenetics,neuronal trac-ing,electrophysiological recordings,and virus knockdown strategies,we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex(S1HL)as well as mechanical hypersensitivity following spared nerve injury(SNI)-induced neuropathic pain in mice.Either pharmaco-logical blockade or virus knockdown of HCN2(shRNA-Hcn2)in the VPL was sufficient to alleviate SNI-induced hyperalgesia.Moreover,shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL-S1HL circuit.Together,our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.展开更多
The sensation of pain is critical for the survival of animals and humans. However, the brain mechanisms underlying pain perception remain largely unknown. How does the brain decode the pain-evoked activity into a part...The sensation of pain is critical for the survival of animals and humans. However, the brain mechanisms underlying pain perception remain largely unknown. How does the brain decode the pain-evoked activity into a particular sensory experience？ Over the past decade, attempts have been made to answer these questions by employing electrophysiological, functional brain imaging, and behavioral approaches, and some basic properties of pain formation have been revealed. Researchers have gradually recognized that there exists a distributed neural network that participates in the transmission and processing of pain information. These studies will further guide the development of more effective treatment for many disorders such as chronic pain.展开更多
基金This work was supported by the National Natural Science Foundation of China(81960216,81903595,81860216,and 32060186)and the Natural Science Foundation of Jiangxi Province(20202BABL206049 and 20202BAB216043).
文摘The thalamocortical(TC)circuit is closely asso-ciated with pain processing.The hyperpolarization-activated cyclic nucleotide-gated(HCN)2 channel is predominantly expressed in the ventral posterolateral thalamus(VPL)that has been shown to mediate neuropathic pain.However,the role of VPL HCN2 in modulating TC circuit activity is largely unknown.Here,by using optogenetics,neuronal trac-ing,electrophysiological recordings,and virus knockdown strategies,we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex(S1HL)as well as mechanical hypersensitivity following spared nerve injury(SNI)-induced neuropathic pain in mice.Either pharmaco-logical blockade or virus knockdown of HCN2(shRNA-Hcn2)in the VPL was sufficient to alleviate SNI-induced hyperalgesia.Moreover,shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL-S1HL circuit.Together,our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.
基金supported by the National Natural Science Foundation of China (No. 30370461,30570577, 30770688, and 30700223)the 100 Talented Plan of the Chinese Academy of Sciences, the 863 project (No.2006AA02Z431)the grant for young scientist from the Chinese Academy of Sciences (No. 07CX051005)
文摘The sensation of pain is critical for the survival of animals and humans. However, the brain mechanisms underlying pain perception remain largely unknown. How does the brain decode the pain-evoked activity into a particular sensory experience？ Over the past decade, attempts have been made to answer these questions by employing electrophysiological, functional brain imaging, and behavioral approaches, and some basic properties of pain formation have been revealed. Researchers have gradually recognized that there exists a distributed neural network that participates in the transmission and processing of pain information. These studies will further guide the development of more effective treatment for many disorders such as chronic pain.
