Article
Neurosciences
Eric Brown, Ayma F. Malik, Elizabeth R. Moese, Abigail F. McElroy, Angelo C. Lepore
Summary: Neuropathic pain (NP) is a common and debilitating comorbidity of spinal cord injury (SCI). This study investigates the neural activity changes in the pain circuitry following cervical spinal cord injury. The findings reveal complex changes in neuronal activation, with increased activation in some neurons and decreased activation in inhibitory neurons.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Rebecca Rani Das Gupta, Louis Scheurer, Pawel Pelczar, Hendrik Wildner, Hanns Ulrich Zeilhofer
Summary: The study revealed that excitatory and inhibitory neurons in the spinal dorsal horn are not only distinguished by gene expression, but also show differential engagement in neuromodulator pathways, especially neuropeptides.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Mira T. Kronschlaeger, Anna S. M. Siegert, Felix J. Resch, Pradeep S. Rajendran, Baljit S. Khakh, Juergen Sandkuehler
Summary: Astrocytes in the dorsal horn of the spinal cord show fine-tuned differences across different layers to meet the demands of processing sensory information of varying modalities. While astrocytes in laminae I and II exhibit higher density and elevated expression levels of certain markers compared to those in lamina III, they share similar membrane properties, network formation, and intracellular calcium signaling characteristics.
Article
Pharmacology & Pharmacy
Fumihiro Saika, Yohji Fukazawa, Shiroh Kishioka, Norikazu Kiguchi
Summary: This study characterizes spinal microglial activation and its association with itch in a mouse model of psoriasis. The findings suggest that sensory neurons contribute to spinal microglial activation.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2023)
Article
Neurosciences
Laura Medlock, Kazutaka Sekiguchi, Sungho Hong, Salvador Dura-Bernal, William W. Lytton, Steven A. Prescott
Summary: Pain-related sensory input is processed in the spinal dorsal horn (SDH) before being relayed to the brain, influencing how stimuli are perceived as painful. Researchers developed a computational model constrained by experimental data to explore SDH function, which reproduced characteristic firing patterns of spinal neurons and responded consistently to inhibition reduction and specific neuron type ablation.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Kwan Yeop Lee, Dongchul Lee, Zachary B. Kagan, Dong Wang, Kerry Bradley
Summary: The study found that low-intensity 10 kHz SCS can inhibit pain-sensory processing in the spinal DH by activating inhibitory interneurons, resulting in paresthesia-free pain relief.
Review
Biochemistry & Molecular Biology
Hanns Ulrich Zeilhofer, Karolina Werynska, Jacinthe Gingras, Gonzalo E. Yevenes
Summary: Restoring proper synaptic inhibition in the spinal cord, particularly through targeting the alpha 3 subtype of glycine receptors, may help reduce deleterious side effects and increase tolerability in chronic pain states. This review provides an update on the physiological properties and functions of alpha 3 subtype GlyRs and related drug discovery programs.
Article
Multidisciplinary Sciences
Tyler S. Nelson, Ghanshyam P. Sinha, Diogo F. S. Santos, Peter Jukkola, Pranav Prasoon, Michelle K. Winter, Ken E. McCarson, Bret N. Smith, Bradley K. Taylor
Summary: Peripheral nerve injury enhances the excitability of Y1-INs in the spinal cord dorsal horn, leading to the development of allodynia and affective pain. Inhibition of Y1-INs or administration of Y1 agonists can alleviate allodynic symptoms. Conditional deletion of Npy1r in dorsal horn neurons prevents the anti-hyperalgesic effects of intrathecal Y1 agonists. These findings suggest that Y1-INs in the spinal cord are a promising target for the treatment of neuropathic pain.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Matthew J. Sykes, Orsolya S. Kekesi, Yan T. Wong, Fei-Yue Zhao, David Spanswick, Wendy L. Imlach
Summary: Acetylcholine plays a crucial role in regulating excitatory and inhibitory synaptic activity in neurons within the spinal dorsal horn. Specific responses to ACh induction in rat and marmoset lamina II neurons show consistent cell-type specific reactions, highlighting the importance of cholinergic signaling in nociception modulation across species.
Article
Anesthesiology
Omer Barkai, Prudhvi Raj Rayi, Rachely Butterman, Ben Katz, Shaya Lev, Alexander M. Binshtok
Summary: Inflammation can enhance the firing of peripheral nociceptive neurons through modifying their input-output properties. The superficial dorsal spinal cord (SDH), the first central nervous system network for processing noxious information, consists of excitatory and inhibitory interneurons and a small number of projection neurons. This study used in vivo calcium imaging and a computational approach to investigate the responsiveness of the SDH network in mice to noxious stimuli and how it changes after acute burn injury-induced inflammation. The findings show that the SDH network exhibits increased activity in response to noxious heat stimuli, and after inflammation, previously nonresponsive neurons are activated and previously suppressed neurons are desuppressed. The study suggests that dynamic changes in the SDH network during acute peripheral inflammation promote hyperalgesia.
Article
Multidisciplinary Sciences
Daniel E. Russ, Ryan B. Patterson Cross, Li Li, Stephanie C. Koch, Kaya J. E. Matson, Archana Yadav, Mor R. Alkaslasi, Dylan Lee, Claire E. Le Pichon, Vilas Menon, Ariel J. Levine
Summary: Single-cell RNA sequencing data is used to generate a comprehensive cell atlas of mouse post-natal spinal cord, revealing the hierarchical relationships among cell types and providing spatial analysis of their distribution. Additionally, an open-source cell type classifier, SeqSeek, is developed to facilitate standardized cell type identification.
NATURE COMMUNICATIONS
(2021)
Article
Anesthesiology
Jie Li, Elizabeth K. Serafin, Mark L. Baccei
Summary: This study investigated the intrinsic and synaptic properties of lamina I spino-PAG neurons and their modulation by neonatal injury. The results showed that the firing of spino-PAG neurons is mainly governed by their intrinsic membrane properties and is resistant to the influence of neonatal tissue damage.
Article
Cell Biology
Filipe A. Monteiro, Rafael M. Miranda, Marta C. Samina, Ana F. Dias, Alexandre A. S. F. Raposo, Patricia Oliveira, Carlos Reguenga, Diogo S. Castro, Deolinda Lima
Summary: The homeobox gene Tlx3 acts as a selector gene in controlling the development of late-born excitatory neurons in the dorsal spinal cord by specifying glutamatergic transmitter fate. Through genomics and validation experiments, it was found that Tlx3 directly activates genes specific to excitatory neurons and also directly represses genes associated with inhibitory neuronal fate. This study provides insight into the regulatory role of Tlx3 in neural development and reveals its novel function in controlling cell identity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Toxicology
Masatake Fujimura, Fusako Usuki, Atsushi Nakamura
Summary: The study revealed that MeHg exposure caused neurological damage in rats, leading to neuropathic pain, mainly through the activation of microglia in the dorsal horn. Furthermore, analysis of the cerebral cortex showed that MeHg exposure could result in the formation of new cortical circuits in specific areas, leading to hyperalgesia/allodynia.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Medicine, Research & Experimental
Wanru Duan, Qian Huang, Fei Yang, Shao-Qiu He, Yun Guan
Summary: This study found that both conventional SCS and 1200 Hz, low-intensity SCS modestly attenuated below-level mechanical hypersensitivity in SCI rats. However, the inhibition of WDR neurons by conventional SCS was not associated with pain inhibition.