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.
Article
Multidisciplinary Sciences
Racheli Wercberger, Joao M. Braz, Jarret A. Weinrich, Allan I. Basbaum
Summary: Using retro-TRAP and RNA sequencing, researchers have uncovered extensive molecular diversity of spino-and trigeminoparabrachial projection neurons, including distinct subsets of gene expression. Further investigation revealed significant functional heterogeneity in these projection neurons, showing convergence and segregation of pain-and itch-provoking inputs into molecularly diverse subsets of NK1R- and non-NK1R-expressing neurons.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Ghanshyam P. Sinha, Pranav Prasoon, Bret N. Smith, Bradley K. Taylor
Summary: The firing patterns of Neuropeptide Y Y1 receptor-expressing neurons in the spinal cord dorsal horn play a crucial role in chronic pain, predominantly controlled by T-type calcium channels. These neurons exhibit rapid adaptation, rebound spiking, and delayed firing, with an adaptation speed higher than other neurons.
JOURNAL OF PHYSIOLOGY-LONDON
(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
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
Cell Biology
Noosha Yousefpour, Samantha Locke, Haley Deamond, Chengyang Wang, Lucas Marques, Manon St-Louis, Johanne Ouellette, Arkady Khoutorsky, Yves De Koninck, Alfredo Ribeiro-da-Silva
Summary: Neuropathic pain is a debilitating condition caused by nerve system damage, and the imbalance of spinal excitation and inhibition is believed to contribute to it. Little is known about the structural basis of this imbalance. Through a preclinical model of neuropathic pain, researchers have found that microglia selectively engulf spinal synapses of central neurons but not peripheral sensory neurons. They also discovered that the removal of inhibitory and excitatory synapses occurs in different temporal patterns, with microglia-mediated inhibitory synapse removal happening before excitatory synapse removal. Additionally, they observed a gradual increase in complement depositions on dorsal horn synapses, which corresponds to the temporal pattern of microglial synapse pruning activity and specific synapse loss.
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
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
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
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
Medicine, Research & Experimental
Ouyang Chen, Qianru He, Qingjian Han, Kenta Furutani, Yun Gu, Madelynne Olexa, Ru-Rong Ji
Summary: Our understanding of neuropathic itch is limited due to a lack of relevant animal models. In this study, we established a mouse model of chronic itch by inoculating cutaneous T cell lymphoma (CTCL) in mice. The model exhibited lymphoma growth, immune cell accumulation, and persistent pruritus. We observed time-dependent changes in nerve innervations and identified different mechanisms underlying acute, chronic, and neuropathic itch.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Neurosciences
Jie Li, Mark L. Baccei
Summary: In a subset of glutamatergic interneurons in the neonatal spinal superficial dorsal horn (SDH), there is intrinsic burst-firing activity regulated by persistent Na+ channels and inward-rectifying K+ channels, which decreases during postnatal development. While ascending lamina I projection neurons targeting the parabrachial nucleus (PB) or periaqueductal gray (PAG) can also display pacemaker activity in early life, the mechanisms driving this activity and its conservation across cell types in the spinal dorsal horn remain unclear. Our study demonstrates that adolescent projection neurons retain the ability to generate pacemaker activity, with differences in membrane properties compared to adjacent neurons lacking intrinsic burst-firing. Further research is needed to understand the mechanisms governing pacemaker activity in the major output neurons of the SDH network.
NEUROSCIENCE LETTERS
(2021)
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
Neurosciences
Javier Lucas-Romero, Ivan Rivera-Arconada, Jose. A. A. Lopez-Garcia
Summary: In this study, the collective behavior of dorsal horn neurons and its relation to backfiring of primary afferents were investigated, along with the effects of peripheral inflammation. The results showed that population bursts of action potentials from neurons presynaptic to the afferents are likely to control their excitability, and peripheral inflammation may enhance the synchrony of these neurons, contributing to central sensitization.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Kwan Yeop Lee, Dongchul Lee, Dong Wang, Zachary B. Kagan, Kerry Bradley
Summary: This study found that simultaneously applying 10 kHz SCS caudally and 40 Hz SCS rostrally may provide greater pain relief than either type of SCS alone. This is because simultaneous stimulation increases the firing rates of inhibitory interneurons, although it also leads to greater activation of excitatory interneurons.
NEUROSCIENCE LETTERS
(2022)