Abnormal Activity of Primary Somatosensory Cortex in Central Pain Syndrome

Quiton, Raimi L.; Masri, Radi; Thompson, Scott M.; Keller, Asaf

doi:10.1152/jn.00161.2010

Cited by 43 publications

(31 citation statements)

References 84 publications

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“…The PO receives somatosensory inputs from the STT and projects to the primary somatosensory cortex [70][71][72][73][74][75], which plays an important role in processing sensory-discriminative aspects of pain [76][77][78][79][80]. Here we show that SCI causes significant increases in both spontaneous firing rates and evoked responses in PO neurons, consistent with prior findings after electrolytic lesions of the spinothalamic tract [24].…”

Section: Discussionsupporting

confidence: 90%

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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Section: Discussionsupporting

confidence: 90%

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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“…1C). The striking reduction in D1 receptor protein expression at 21 days (32.7 ± 3.7% of Sham control) was associated with significant changes in behavioral indicators of hypersensitivity in rats observed after SCL, measured at the same time points as we have shown previously (Masri et al, 2009; Quiton et al, 2010; Seminowicz et al, 2012; Jiang et al, 2016). …”

Section: Resultssupporting

confidence: 76%

“…The decrease in D1 receptor protein expression 7 and 21 days after SCL was associated with a reduction in mechanical sensitivity, reflected in hindlimb mechanical withdrawal thresholds using von Frey filaments in both rats (Quiton et al, 2010; Seminowicz et al, 2012; Jiang et al, 2016) and mice (Fig. 2A).…”

Section: Discussionmentioning

confidence: 93%

Loss of dopamine D1 receptors and diminished D1/5 receptor-mediated ERK phosphorylation in the periaqueductal gray after spinal cord lesion

Voulalas

Jiang

et al. 2017

Neuroscience

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Neuropathic pain resulting from spinal cord injury is often accompanied by maladaptive plasticity of the central nervous system, including the opioid receptor-rich periaqueductal gray (PAG). Evidence suggests that sensory signaling via the PAG is robustly modulated by dopamine D1- and D2-like receptors, but the effect of damage to the spinal cord on D1 and D2 receptor protein expression and function in the PAG has not been examined. Here we show that 21 days after a T10 or C6 spinothalamic tract lesion, both mice and rats display a remarkable decline in the expression of D1 receptors in the PAG, revealed by western blot analysis. These changes were associated with a significant reduction in hindpaw withdrawal thresholds in lesioned animals compared to sham-operated controls. We investigated the consequences of diminished D1 receptor levels by quantifying D1-like receptor-mediated phosphorylation of ERK1,2 and CREB, events that have been observed in numerous brain structures. In naïve animals, western blot analysis revealed that ERK1,2, but not CREB phosphorylation was significantly increased in the PAG by the D1-like agonist SKF 81297. Using immunohistochemistry, we found that SKF 81297 increased ERK1,2 phosphorylation in the PAG of sham animals. However, in lesioned animals, basal pERK1,2 levels were elevated and did not significantly increase after exposure to SKF 81297. Our findings provide support for the hypothesis that molecular adaptions resulting in a decrease in D1 receptor expression and signaling in the PAG are a consequence of SCL.

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“…The fact that our results were significant only with high intensity stimuli – which likely activate both the dorsal columns and the spinothalamic tract [27,37] – and not with low-intensity stimuli – which likely activate only the dorsal columns [27,37] – suggests that the subcortical interaction between lemniscal and paralemniscal systems [65,66] might play a role in our experimental model [45]. Nonetheless, subcortical reorganization could in principle occur either in the thalamus [45,67–69], in the brainstem [67,69–71], or even within the spinal cord [72,73].…”

Section: Discussionmentioning

confidence: 99%

Reorganization of the Intact Somatosensory Cortex Immediately after Spinal Cord Injury

2013

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Sensory deafferentation produces extensive reorganization of the corresponding deafferented cortex. Little is known, however, about the role of the adjacent intact cortex in this reorganization. Here we show that a complete thoracic transection of the spinal cord immediately increases the responses of the intact forepaw cortex to forepaw stimuli (above the level of the lesion) in anesthetized rats. These increased forepaw responses were independent of the global changes in cortical state induced by the spinal cord transection described in our previous work (Aguilar et al., J Neurosci 2010), as the responses increased both when the cortex was in a silent state (down-state) or in an active state (up-state). The increased responses in the intact forepaw cortex correlated with increased responses in the deafferented hindpaw cortex, suggesting that they could represent different points of view of the same immediate state-independent functional reorganization of the primary somatosensory cortex after spinal cord injury. Collectively, the results of the present study and of our previous study suggest that both state-dependent and state-independent mechanisms can jointly contribute to cortical reorganization immediately after spinal cord injury.

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Abnormal Activity of Primary Somatosensory Cortex in Central Pain Syndrome

Cited by 43 publications

References 84 publications

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

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

Loss of dopamine D1 receptors and diminished D1/5 receptor-mediated ERK phosphorylation in the periaqueductal gray after spinal cord lesion

Reorganization of the Intact Somatosensory Cortex Immediately after Spinal Cord Injury

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