Bilateral hyperexcitability of thalamic VPL neurons following unilateral spinal injury in rats

Gwak, Young Seob; Kim, Hee Kee; Kim, Hee Young; Leem, Joong Woo

doi:10.1007/s12576-009-0066-2

Cited by 30 publications

(17 citation statements)

References 38 publications

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“…1,4 In addition, we and others have reported that hemisection results in bilateral hyperexcitability of the thalamic VPL neurons, whereas SNL produces hyperexcitability in the contralateral side of the thalamic VPL neurons. 12,13 The present study, combined with previous results, suggests that spinal hemisection produces bilateral neuropathic pain, whereas spinal nerve ligation produces unilateral neuropathic pain that runs through pathways including the spinal dorsal horn neurons, gracile neurons, and thalamic VPL neurons.…”

Section: Discussionsupporting

confidence: 79%

“…We and others have reported that hyperexcitability of the thalamic VPL neurons contributes to mechanical allodynia in the hindpaw, which includes similar mechanisms of neuropathic pain in the spinal dorsal horn. 12,13 In contrast to STTs, DC-MLs mediate non-noxious inputs to the supraspinal site of the gracile nucleus, and is considered an important ascending pathway for mechanical allodynia. However, the contribution of gracile neurons to the neuropathic pain seen with peripheral and spinal cord injuries remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Gracile Neurons Contribute to the Maintenance of Neuropathic Pain in Peripheral and Central Neuropathic Models

Kim

Wang

Gwak

2012

Journal of Neurotrauma

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In the present study, we compared the roles of gracile neurons in mechanically-induced neuropathic pain caused by spinal injury and L5 spinal nerve ligation in rats. Behavioral and electrophysiological methods were used to measure mechanical allodynia in the hindpaws, and excitability of the gracile neurons in the medulla, respectively. In the spinal hemisection and spinal contusion models, mechanical allodynia developed in both hindpaws and lasted over a month. Three weeks following the hemisection, gracile neurons identified as wide-dynamic-range (WDR) and low-threshold (LT) neurons, showed increased neuronal activity to non-noxious mechanical stimuli compared to control groups, whereas the spinal contusion groups did not show evoked activity (*p<0.05). A lesion of the gracile nucleus partially reversed the existing mechanical allodynia in both hindpaws compared to prior to the injury in the hemisection group, whereas the spinal contusion groups did not show significant changes (*p<0.05). In the spinal nerve ligation model, mechanical allodynia developed at the ipsilateral (injured) side of the hindpaw. In addition, WDR neuronal activity at the ipsilateral gracile neurons showed a significant increase with non-noxious mechanical stimuli, whereas the LT neurons did not show significant changes (*p<0.05). Similarly to the hemisection model, a lesion of the gracile nucleus attenuated the mechanical allodynia in spinal nerve ligation models. The present data suggest that gracile neurons contribute to the maintenance of non-noxious mechanically-induced neuropathic pain in both hemisection- and ligation-induced neuropathic pain in rats.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Gracile Neurons Contribute to the Maintenance of Neuropathic Pain in Peripheral and Central Neuropathic Models

Kim

Wang

Gwak

2012

Journal of Neurotrauma

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“…The altered recognition of sensory input produces changes of distributional proportions after SCI. However, electrophysiological data suggest that WDR neurons do not lose their response properties to different sensory modalities; alterations in response to different sensory modalities produce an increase, rather than a decrease, in the proportion of WDR neurons in both the spinal dorsal horn and the thalamic VPL region after SCI [19,24]. However, the alterations of the electrophysiological response properties of dorsal horn neurons are not the only important factor contributing to neuronal hyperexcitability and proportional changes; neuroanatomical changes also are an important substrate in the spinal dorsal horn after SCI (see below).…”

Section: Hyperexcitability Of Spinal Dorsal Horn Neurons After Spinalmentioning

confidence: 99%

“…Thus, the reorganization of synaptic circuits contributes to hyperexcitability in both spinal and supraspinal regions after SCI. The hyperexcitability of VPL neurons suggests that supraspinal mechanisms also are important in contributing to CNP after SCI [19,20].…”

Section: Reorganization Of Synaptic Circuits In Spinal Dorsal Horn Afmentioning

confidence: 99%

Neuronal Hyperexcitability: A Substrate for Central Neuropathic Pain After Spinal Cord Injury

Gwak

Hulsebosch

2011

Curr Pain Headache Rep

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Neuronal hyperexcitability produces enhanced pain transmission in the spinal dorsal horn after spinal cord injury (SCI). Spontaneous and evoked neuronal excitability normally are well controlled by neural circuits. However, SCI produces maladaptive synaptic circuits in the spinal dorsal horn that result in neuronal hyperexcitability. After SCI, activated primary afferent neurons produce enhanced release of glutamate, neuropeptides, adenosine triphosphate, and proinflammatory cytokines, which are known to be major components for pain transmission in the spinal dorsal horn. Enhanced neurochemical events contribute to neuronal hyperexcitability, and neuroanatomical changes also contribute to maladaptive synaptic circuits and neuronal hyperexcitability. These neurochemical and neuroanatomical changes produce enhanced cellular signaling cascades that ensure persistently enhanced pain transmission. This review describes altered neurochemical and neuroanatomical contributions on neuronal hyperexcitability in the spinal dorsal horn, which serve as substrates for central neuropathic pain after SCI.

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“…Such changes have been implicated in the induction and maintenance of SCI pain. Identification of molecular mechanisms underlying this "gliopathy" [29,31,32] may therefore help to clarify the pathobiology of SCI pain and lead to the elucidation of novel therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Cell Cycle Activation Contributes to Increased Neuronal Activity in the Posterior Thalamic Nucleus and Associated Chronic Hyperesthesia after Rat Spinal Cord Contusion

Raver

Piao

et al. 2013

Neurotherapeutics

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Spinal cord injury (SCI) causes not only sensorimotor and cognitive deficits, but frequently also severe chronic pain that is difficult to treat (SCI pain). We previously showed that hyperesthesia, as well as spontaneous pain induced by electrolytic lesions in the rat spinothalamic tract, is associated with increased spontaneous and sensory-evoked activity in the posterior thalamic nucleus (PO). We have also demonstrated that rodent impact SCI increases cell cycle activation (CCA) in the injury region and that post-traumatic treatment with cyclin dependent kinase inhibitors reduces lesion volume and motor dysfunction. Here we examined whether CCA contributes to neuronal hyperexcitability of PO and hyperpathia after rat contusion SCI, as well as to microglial and astroglial activation (gliopathy) that has been implicated in delayed SCI pain. Trauma caused enhanced pain sensitivity, which developed weeks after injury and was correlated with increased PO neuronal activity. Increased CCA was found at the thoracic spinal lesion site, the lumbar dorsal horn, and the PO. Increased microglial activation and cysteine-cysteine chemokine ligand 21 expression was also observed in the PO after SCI. In vitro, neurons co-cultured with activated microglia showed up-regulation of cyclin D1 and cysteine-cysteine chemokine ligand 21 expression. In vivo, post-injury treatment with a selective cyclin dependent kinase inhibitor (CR8) significantly reduced cell cycle protein induction, microglial activation, and neuronal activity in the PO nucleus, as well as limiting chronic SCI-induced hyperpathia. These results suggest a mechanistic role for CCA in the development of SCI pain, through effects mediated in part by the PO nucleus. Moreover, cell cycle modulation may provide an effective therapeutic strategy to improve reduce both hyperpathia and motor dysfunction after SCI.

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Bilateral hyperexcitability of thalamic VPL neurons following unilateral spinal injury in rats

Cited by 30 publications

References 38 publications

Gracile Neurons Contribute to the Maintenance of Neuropathic Pain in Peripheral and Central Neuropathic Models

Gracile Neurons Contribute to the Maintenance of Neuropathic Pain in Peripheral and Central Neuropathic Models

Neuronal Hyperexcitability: A Substrate for Central Neuropathic Pain After Spinal Cord Injury

Cell Cycle Activation Contributes to Increased Neuronal Activity in the Posterior Thalamic Nucleus and Associated Chronic Hyperesthesia after Rat Spinal Cord Contusion

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