Selective-cold output through a distinct subset of lamina I spinoparabrachial neurons

Hachisuka, Junichi; Koerber, H. Richard; Ross, Sarah E.

doi:10.1097/j.pain.0000000000001710

Cited by 37 publications

(51 citation statements)

References 56 publications

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“…3), and ability to directly inhibit lamina I projection neurons (Fig. 6) (Hachisuka et al, 2020), it seems highly likely that spinal DYN-lineage neurons represent a critical component of this feedforward inhibitory pathway linking primary sensory neurons to projection neurons.…”

Section: Discussionmentioning

confidence: 99%

“…For example, interneurons characterized by the expression of dynorphin (DYN) have been implicated in suppressing itch (Kardon et al, 2014;Huang et al, 2018) and mechanical pain (Duan et al, 2014). Furthermore, DYN interneurons are highly prevalent in the DH (Boyle et al, 2017) and synapse directly onto lamina I projection neurons (Hachisuka et al, 2020). As a result, it is possible that persistent deficits in the function of spinal DYN circuits in the aftermath of neonatal tissue damage could contribute to both the reduction in FFI onto adult spinoparabrachial neurons (Li et al, 2015) and the exacerbation of mechanical pain hypersensitivity following subsequent injury, the latter of which is a hallmark feature of neonatal priming (Walker et al, 2009(Walker et al, , 2015.…”

Section: Introductionmentioning

confidence: 99%

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Neonatal Injury Evokes Persistent Deficits in Dynorphin Inhibitory Circuits within the Adult Mouse Superficial Dorsal Horn

Brewer

O’Conor

et al. 2020

J. Neurosci.

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Neonatal tissue damage induces long-term deficits in inhibitory synaptic transmission within the spinal superficial dorsal horn (SDH) that include a reduction in primary afferent-evoked, feedforward inhibition onto adult projection neurons. However, the subpopulations of mature GABAergic interneurons which are compromised by early-life injury have yet to be identified. The present research illuminates the persistent effects of neonatal surgical injury on the function of inhibitory SDH interneurons derived from the prodynorphin (DYN) lineage, a population that synapses directly onto lamina I spinoparabrachial neurons and is known to suppress mechanical pain and itch in adults. The results demonstrate that hindpaw incision at postnatal day 3 (P3) significantly decreased the strength of primary afferent-evoked glutamatergic drive onto DYN neurons within the adult mouse SDH while increasing the appearance of afferent-evoked inhibition onto the same population. Neonatal injury also dampened the intrinsic membrane excitability of mature DYN neurons, and reduced their action potential discharge in response to sensory input, compared with naive littermate controls. Furthermore, P3 incision decreased the efficacy of inhibitory DYN synapses onto adult spinoparabrachial neurons, which reflected a prolonged reduction in the probability of GABA release. Collectively, the data suggest that early-life tissue damage may persistently constrain the ability of spinal DYN interneurons to limit ascending nociceptive transmission to the adult brain. This is predicted to contribute to the loss of feedforward inhibition onto mature projection neurons, and the "priming" of nociceptive circuits in the developing spinal cord, following injuries during the neonatal period.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neonatal Injury Evokes Persistent Deficits in Dynorphin Inhibitory Circuits within the Adult Mouse Superficial Dorsal Horn

Brewer

O’Conor

et al. 2020

J. Neurosci.

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“…Thus, while inhibition of CeA-PKCδ neurons reversed cuff-induced hypersensitivity to tactile, cold and heat hypersensitivity (Wilson et al, 2019), chemogenetic activation of ZI GABAergic neurons only reversed cuff-induced pinch, but not cold or thermal, hypersensitivity ( Figure 6-7 ). Previous studies have shown that responses of spinoparabrachial neurons are modality-specific (Hachisuka et al, 2020). Our results raise the interesting possibility that subpopulations CeA-PKCδ neurons might also be recruited in a modality-specific manner, with CeA-PKCδ neurons that project to the ZI selectively responding to tactile but not thermal stimulation.…”

Section: Discussionmentioning

confidence: 99%

Bidirectional modulation of pain-related behaviors in the zona incerta

Singh

Valdivia

Soler-Cedeño

et al. 2021

Preprint

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Central amygdala neurons expressing protein kinase C-delta (CeA-PKCδ) are sensitized following nerve injury and promote pain-related responses in mice. The neural circuits underlying modulation of pain-related behaviors by CeA-PKCδ neurons, however, remain unknown. In this study, we identified a functional monosynaptic inhibitory neural circuit that originates in CeA-PKCδ neurons and terminates in the ventral region of the zona incerta (ZI), a subthalamic structure previously linked to pain processing. Behavioral experiments further show that chemogenetic inhibition of GABAergic ZI neurons is sufficient to induce bilateral hypersensitivity in uninjured mice as well as contralateral hypersensitivity after nerve injury. In contrast, chemogenetic activation of GABAergic ZI neurons reverses nerve injury-induced hypersensitivity, demonstrating that silencing of the ZI is required for injury-induced behavioral hypersensitivity. Our results identify a previously unrecognized inhibitory efferent pathway from CeA-PKCδ neurons to the ZI and demonstrate that ZI-GABAergic neurons can bidirectionally modulate pain-related behaviors in mice.

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“…6, 7) to 5Hz producing a 17.42 ±0.06 Hz EPSC frequency to reach a capsaicin-mediated elevation of EPSC frequency in control conditions in SDH neurons (McCoy et al, 2013). For injury conditions, we increased the external input to 12 Hz, leading to a 61.52 ±0.14 Hz EPSC frequency, reaching the higher rates mentioned in published literature (Bardoni et al, 2019;Hachisuka et al, 2020). 70% of randomly chose SDH neurons received external inputs (Wang et al, 2018).…”

Section: Computational Modelmentioning

confidence: 91%

Encoding of inflammatory hyperalgesia in mice spinal cord

Barkai

Butterman

Katz

et al. 2021

Preprint

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Inflammation modifies the input-output properties of peripheral nociceptive neurons, thus leading to hyperalgesia, i.e., changes in the perception of noxious heat stimuli such that the same stimulus produces enhanced pain. The increased nociceptive output enters the superficial dorsal spinal cord (SDH), which comprises the first CNS network integrating the noxious information. Here we used in vivo calcium imaging and a computational approach to investigate how the SDH network in mice encodes the injury-mediated abnormal input from peripheral nociceptive neurons. We show the application of noxious heat stimuli to the mice hind paw in naive conditions before induction of injury affects the activity of 70% of recorded neurons by either increasing or suppressing it. Application of the same noxious heat stimuli to hyperalgesic skin leads to activation of previously non-responded cells and de-suppression of the "suppressed" neurons. We demonstrate that reduction in synaptic inhibition mimics the response to the noxious stimuli in the hyperalgesic conditions. Using a computational model of SDH network, we predict that inflammation-induced "disinhibition"-like changes result in increased activity of excitatory projection neurons. Our model also predicts that the observed "disinhibitory" effect of hyperalgesic stimuli does not require changes in the inhibitory transmission and may result from the SDH networks' intrinsic cytoarchitecture.

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Selective-cold output through a distinct subset of lamina I spinoparabrachial neurons

Abstract: The material cannot be used for any other purpose without further permission of the publisher and is for private use only. There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.

Cited by 37 publications

References 56 publications

Neonatal Injury Evokes Persistent Deficits in Dynorphin Inhibitory Circuits within the Adult Mouse Superficial Dorsal Horn

Neonatal Injury Evokes Persistent Deficits in Dynorphin Inhibitory Circuits within the Adult Mouse Superficial Dorsal Horn

Bidirectional modulation of pain-related behaviors in the zona incerta

Encoding of inflammatory hyperalgesia in mice spinal cord

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