Article
Anesthesiology
Elisabete C. Fernandes, Jose Carlos-Ferreira, Liliana L. Luz, Eva Kokai, Zoltan Meszar, Peter Szucs, Boris Safronov
Summary: This study used an ex vivo brainstem-cervical cord preparation to investigate the input from C2 spinal nerve and trigeminal nerve to upper cervical lamina I neurons. The results showed that these neurons receive monosynaptic input from both nerves, with more inhibitory inputs coming from the trigeminal nerve.
Article
Neurosciences
Liliana L. Luz, Susana Lima, Elisabete C. Fernandes, Eva Kokai, Lidia Gomori, Peter Szucs, Boris V. Safronov
Summary: Mirror-image pain arises from pathologic alterations in the nociceptive processing network that controls functional lateralization of the primary afferent input. Our study reveals that decussating primary afferent branches reach contralateral Lamina I, where neurons receive excitatory drive from the contralateral fibers and also ipsilateral input, implying their involvement in bilateral information processing. The contralateral fiber input is under inhibitory control, and a pathological disinhibition of the decussating pathways can contribute to induction of hypersensitivity and mirror-image pain.
JOURNAL OF NEUROSCIENCE
(2023)
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
Neurosciences
Jesse K. Niehaus, Bonnie Taylor-Blake, Lipin Loo, Jeremy M. Simon, Mark J. Zylka
Summary: Peripheral nerve injury leads to long-term pro-inflammatory responses in spinal cord glial cells, but the identity of endogenous cells that resolve spinal inflammation has not been determined. Our study demonstrates that MRC1(+) spinal cord macrophages actively restrain glia to limit neuroinflammation and resolve mechanical pain following superficial injury, suggesting that therapeutic modulation of spinal macrophages could promote long-lasting recovery of neuropathic pain.
Article
Multidisciplinary Sciences
Kevin J. Pollard, Devon A. Bowser, Wesley A. Anderson, Mostafa Meselhe, Michael J. Moore
Summary: Chronic pain is on the rise due to genetic predisposition, injury, or acquired neuropathy. Opioid analgesics, while effective, have led to an epidemic of prescription drug abuse. Screening drug candidates in a microphysiological system can efficiently identify therapeutics with analgesic potential.
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
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
Anesthesiology
Noemie Mermet-Joret, Cristina Alba-Delgado, Amelie Descheemaeker, Francois Gabrielli, Radhouane Dallel, Myriam Antri
Summary: Pain processing is immature in young mammals. The development of neurons in the medullary dorsal horn (MDH) has been overlooked. In this study, we investigate the age-dependent development of neurons in the inner lamina II (IIi) of the MDH in rats. We found that these neurons undergo physiological and structural changes, which are associated with facial mechanical allodynia.
Article
Neurosciences
Eric Brown, Aditi Falnikar, Nicolette Heinsinger, Lan Cheng, Carrie E. Andrews, Michael DeMarco, Angelo C. Lepore
Summary: The study revealed significant MM phi heterogeneity within and across pain transmission locations after SCI, including a prominent pro-inflammatory MM phi response in the sDH of cervical spinal cord. These data suggest a possible role for MM phi in DH neuron hyperexcitability and NP.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Neurosciences
Laszlo Ducza, Andrea Gajtko, Krisztina Hegedus, Erzsebet Bakk, Greta Kis, Botond Gaal, Roland Takacs, Peter Szucs, Klara Matesz, Krisztina Hollo
Summary: This study provides new evidence for the involvement of neuronal and glial P2X4 receptors in the development of inflammatory pain.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Elisabete C. Fernandes, Jose Carlos-Ferreira, Liliana L. Luz, Boris Safronov
Summary: Cervical and trigeminal afferents interact via presynaptic inhibition, shaping the way sensory input reaches neurons. Disruption of this inhibition may contribute to the development of primary headache syndromes.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Andrew H. Cooper, Naomi S. Hedden, Pranav Prasoon, Yanmei Qi, Bradley K. Taylor
Summary: Following tissue injury, latent sensitization can be maintained in remission by the activity of μ-opioid receptors in the spinal cord. This sensitization is mediated by serotonergic neurons in the rostral ventral medulla that convey pronociceptive input to the spinal cord. The 5-HT3 receptor signaling in the dorsal horn and the activity of μ-opioid receptors in the rostral ventral medulla play opposing roles in maintaining this sensitization.
JOURNAL OF NEUROSCIENCE
(2022)
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
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
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
Anesthesiology
Elisabete C. Fernandes, Jose Carlos-Ferreira, Liliana L. Luz, Eva Kokai, Zoltan Meszar, Peter Szucs, Boris Safronov
Summary: This study used an ex vivo brainstem-cervical cord preparation to investigate the input from C2 spinal nerve and trigeminal nerve to upper cervical lamina I neurons. The results showed that these neurons receive monosynaptic input from both nerves, with more inhibitory inputs coming from the trigeminal nerve.
Article
Cell Biology
Joana Nogueira-Rodrigues, Sergio C. Leite, Rita Pinto-Costa, Sara C. Sousa, Liliana L. Luz, Maria A. Sintra, Raquel Oliveira, Ana C. Monteiro, Goncalo G. Pinheiro, Marta Vitorino, Joana A. Silva, Sonia Simao, Vitor E. Fernandes, Jan Provaznik, Vladimir Benes, Celia D. Cruz, Boris Safronov, Ana Magalhaes, Celso A. Reis, Jorge Vieira, Cristina P. Vieira, Gustavo Tiscornia, Ines M. Araujo, Monica M. Sousa
Summary: The spiny mouse is capable of spontaneous and fast restoration of function after severe spinal cord injury (SCI) due to the formation of scarless regenerative tissue. Transcriptomic analysis revealed the rewiring of glycosylation biosynthetic pathways in the spiny mouse, leading to pro-regenerative proteoglycan signature at the SCI site. This study highlights the importance of glycosylation switch in axon regeneration after SCI.
DEVELOPMENTAL CELL
(2022)
Article
Biochemistry & Molecular Biology
Rashmi Kumari, Emese A. Fazekas, Boglarka Morvai, Edina B. Udvari, Fanni Dora, Gergely Zachar, Tamas Szekely, Akos Pogany, Arpad Dobolyi
Summary: By studying gene expression in caring and non-caring female zebra finches, the study identified the importance of dopamine and acetylcholine biosynthetic processes in parental care and suggested neuro-immunological changes in mothers as potential factors contributing to parenting behavior.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Elisabete C. Fernandes, Jose Carlos-Ferreira, Liliana L. Luz, Boris Safronov
Summary: Cervical and trigeminal afferents interact via presynaptic inhibition, shaping the way sensory input reaches neurons. Disruption of this inhibition may contribute to the development of primary headache syndromes.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Fanni Dora, Eva Renner, David Keller, Miklos Palkovits, Arpad Dobolyi
Summary: This study revealed extensive gene expressional alterations in the dorsomedial prefrontal cortex (DMPFC) related to suicidal behavior. Genes associated with depressive disorder, schizophrenia, and impaired cognition were found to be overexpressed, while pathways related to cytokine receptor signaling were downregulated and glutamatergic synaptic signaling were upregulated in suicide victims.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
David Keller, Tamas Lang, Melinda Cservenak, Gina Puska, Janos Barna, Veronika Csillag, Imre Farkas, Dora Zelena, Fanni Dora, Stephanie Kuppers, Lara Barteczko, Ted B. Usdin, Miklos Palkovits, Mazahir T. Hasan, Valery Grinevich, Arpad Dobolyi
Summary: This study discovered a neuronal pathway from PIL to MPOA that plays an important role in the control of social grooming. The activation of PIL and MPOA neurons by physical contact and chemogenetic stimulation indicates their involvement in social grooming. Additionally, the activation of the PIL-MPOA pathway and the expression of the neuropeptide PTH2 were found to facilitate social grooming.
Article
Neurosciences
Eva Kokai, Lilana L. Luz, Elisabete C. Fernandes, Boris Safronov, Pierrick Poisbeau, Peter Szucs
Summary: Our knowledge about the detailed wiring of neuronal circuits in the spinal dorsal horn, where initial sensory processing takes place, is still very sparse. In this study, the researchers reconstructed the axonal and dendritic processes of projection neurons and interneurons in lamina I of the rat, and investigated their distribution patterns and functional roles. They found that the axon collateral distribution patterns of projection neurons and interneurons are distinct, with projection neurons dominating the dorsolateral funiculus and interneurons establishing local connections in lamina I. The whole-cell patch-clamp recordings confirmed the excitatory drive mediated by neurokinin-1 receptors in projection neurons. These findings provide valuable insights into the organization of neuronal circuits in the spinal dorsal horn.
JOURNAL OF COMPARATIVE NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Orsolya Somogyi, Zsolt Dajnoki, Lilla Szabo, Krisztian Gaspar, Zoltan Hendrik, Christos C. Zouboulis, Klaudia Docs, Peter Szucs, Katalin Dull, Daniel Torocsik, Aniko Kapitany, Andrea Szegedi
Summary: By comparing non-lesional HS skin, lesional HS skin, and healthy skin, the study found that none of the investigated molecules were significantly altered in non-lesional HS skin, while 11 molecules changed significantly in lesional HS skin. The study also showed that the permeability barrier function was not significantly damaged in HS skin, and permeability barrier alterations are not the driver factors of keratinocyte activation in this disease.
Article
Neurosciences
Liliana L. Luz, Susana Lima, Elisabete C. Fernandes, Eva Kokai, Lidia Gomori, Peter Szucs, Boris V. Safronov
Summary: Mirror-image pain arises from pathologic alterations in the nociceptive processing network that controls functional lateralization of the primary afferent input. Our study reveals that decussating primary afferent branches reach contralateral Lamina I, where neurons receive excitatory drive from the contralateral fibers and also ipsilateral input, implying their involvement in bilateral information processing. The contralateral fiber input is under inhibitory control, and a pathological disinhibition of the decussating pathways can contribute to induction of hypersensitivity and mirror-image pain.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Vivien Csikos, Szilvia Olah, Fanni Dora, Nikolett Arrasz, Melinda Cservenak, Arpad Dobolyi
Summary: Microglial cells are necessary for prolactin secretion and lactation, while maternal motivation may not be directly affected by microglia. Inhibition of colony stimulating factor 1 receptor using Pexidartinib 3397 eliminated microglial cells from the brain. Mothers treated with PLX3397 during the prepartum period did not feed their pups after giving birth. The weight gain of foster pups during a suckling bout was reduced in mothers fed with PLX3397 and in rat dams treated with PLX3397, suggesting that lactation was affected by the decrease in microglia.
Article
Clinical Neurology
Ana Nascimento, Tiago F. Da Silva, Elisabete C. Fernandes, Liliana L. Luz, Fernando M. Mar, Boris Safronov, Monica M. Sousa
Summary: This study reveals the presence of axon initial segments (AIS) in sensory dorsal root ganglion (DRG) neurons and their role in spontaneous discharges in neuropathic pain. The AIS in myelinated DRG neurons contains sodium channels that are associated with spontaneous activity. Computer simulations suggest that the AIS plays a crucial role in initiating spontaneous discharges. The disruption of the AIS leads to mechanical allodynia in neuropathic pain, indicating its significance in chronic pain management.