2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
April 1st, 2025
Version: 1
University of Texas at Dallas
neuroscience
biorxiv

Expansion of OSMR expression and signaling in the human dorsal root ganglion links OSM to neuropathic pain

Mwirigi, J. M.Open in Google Scholar•Sankaranarayanan, I.Open in Google Scholar•Tavares-Ferreira, D.Open in Google Scholar•Gabriel, K. A.Open in Google Scholar•Palomino, S.Open in Google Scholar•Li, Y.Open in Google Scholar•Uhelski, M. L.Open in Google Scholar•Shiers, S.Open in Google Scholar•Franco-Enzastiga, U.Open in Google Scholar•Wangzhou, A.Open in Google Scholaret al.

RNA sequencing studies on human dorsal root ganglion (hDRG) from patients suffering from neuropathic pain show upregulation of OSM, linking this IL-6 family cytokine to pain disorders. In mice, however, OSM signaling causes itch behaviors through a direct effect on its cognate receptor expressed uniquely by pruriceptive sensory neurons. We hypothesized that an expansion in function of OSM-OSM receptor (OSMR) in sensory disorders in humans could be explained by species differences in receptor expression and signaling. Our in situ hybridization and immunohistochemical findings demonstrate broad expression of OSMR in DRG nociceptors and afferent fibers innervating the superficial and deep skin of humans. In patch-clamp electrophysiology, OSM directly activates human sensory neurons engaging MAPK signaling to promote action potential firing. Using CRISPR editing we show that OSM activation of MAPK signaling is dependent on OSMR and not LIFR in hDRG. Bulk, single-nuclei, and single-cell RNA-seq of OSM-treated hDRG cultures reveal expansive similarities in the transcriptomic signature observed in pain DRGs from neuropathic patients, indicating that OSM alone can orchestrate transcriptomic signatures associated with pain. We conclude that OSM-OSMR signaling via MAPKs is a critical signaling factor for DRG plasticity that may underlie neuropathic pain in patients.

Similar Papers

biorxiv
Wed Apr 02 2025
Alternative splicing generates a Ribosomal Protein S24 isoform induced by neuroinflammation and neurodegeneration
Neuroinflammation, particularly that involving reactive microglia, the brain\'s resident immune cells, is implicated in the pathogenesis of major neurodegenerative diseases. However, early markers of this process are in high demand. Multiple studies have reported changes in ribosomal protein (RP) expression during neurodegeneration, but the significance of these changes remains unclear. Ribosomes ...
Magadi, S. S.
•
Jonson, M.
•
Maqdissi, J. A.
•
Kaczmarczyk, L.
...•
Jackson, W. S.
biorxiv
Wed Apr 02 2025
Synergistic reinforcement learning by cooperation of the cerebellum and basal ganglia
The cerebral cortex, cerebellum and basal ganglia are essential for flexible learning in mammals. Although traditionally thought to operate under different learning rules, recent evidence suggests that both the basal ganglia and the cerebellum may employ reinforcement learning mechanisms. This raises the question of how these structures coordinate when a common reward prediction error mechanism is...
Yohida, T.
•
Sugino, H.
•
Yamamoto, H.
•
Tanno, S.
...•
Hira, R.
biorxiv
Wed Apr 02 2025
Substrate stiffness and shear stress collectively regulate the inflammatory phenotype in cultured human brain microvascular endothelial cells
Brain endothelial cells experience mechanical forces in the form of blood flow-mediated shear stress and underlying matrix stiffness, but intersectional contributions of these factors towards blood-brain barrier (BBB) impairment and neurovascular dysfunction have not been extensively studied. Here, we developed in vitro models to examine the sensitivity of primary human brain microvascular endothe...
Yates, A.
•
Murray, H.
•
Kjar, A.
•
Chavarria, D.
...•
Lippmann, E.
biorxiv
Wed Apr 02 2025
A novel critic signal in identified midbrain dopaminergic neurons of mice training in operant tasks
In the canonical interpretation of dopaminergic neuron activity during Pavlovian conditioning, initially cell firing is triggered by unexpected rewards. Upon learning, activation instead follows the reward-predictive conditioned stimulus, and when expected rewards are withheld, firing is inhibited. However, little is known about dopaminergic neuron activity during the actual learning process in op...
Matsumoto, J.
•
Oberto, V.
•
Pompili, M. N.
•
Todorova, R.
...•
Wiener, S. I.
biorxiv
Wed Apr 02 2025
Progressive multi-stage extrapolation of predictable motion in human visual cortex
Neural processing of sensory information takes time. Consequently, to estimate the current state of the world, the brain must rely on predictive processes - for example, extrapolating the motion of a ball to determine its probable present position. Some evidence implicates early (pre-cortical) processing in extrapolation, but it remains unclear whether extrapolation continues during later-stage (c...
Turner, W.
•
Sexton, C.
•
Johnson, P. A.
•
Wilson, E.
•
Hogendoorn, H.
biorxiv
Wed Apr 02 2025
Hierarchical Processing of Natural Scenes in the Human Pulvinar
The hierarchical organization of the ventral visual cortex has been the focus of theories and computational models characterizing high-level visual processing and object recognition, often overlooking potential contributions of subcortical structures. The pulvinar, through its extensive reciprocal connections with ventral visual cortex, is well-positioned to play a prominent role in high-level vis...
Guest, D. R.
•
Allen, E. J.
•
Kay, K. N.
•
Arcaro, M. J.
biorxiv
Wed Apr 02 2025
Ykt6 SNARE protein drives GluA1 insertion at synaptic spines during LTP
Long-Term Potentiation (LTP), a crucial form of synaptic plasticity essential for memory and learning, depends on protein synthesis and the upregulation of GluA1 at postsynaptic terminals. While extensive research has focused on the role of endosomal trafficking in GluA1 regulation, the contribution of endoplasmic reticulum (ER) trafficking pathways remains largely unexplored. A key opportunity to...
Takahashi, M.
•
Caraveo, G.
biorxiv
Wed Apr 02 2025
Released mitochondrial DNA and neurofilament light chain as Parkinson's disease phenotypes in patient-specific midbrain assembloids
Parkinson's Disease is the second most common neurodegenerative disorder worldwide, with growing numbers and considerable societal and economic concerns. Human cell culture systems are efficient models for neurodegenerative disorders and allow for personalized, non-invasive analysis of cellular and molecular disease mechanisms. Midbrain organoids and assembloids are advanced 3D culture systems tha...
Sabate-Soler, S.
•
Rosety, I.
•
Gomez-Giro, G.
•
Ghelfi, J.
...•
Jarazo, J.
biorxiv
Wed Apr 02 2025
Olfactory dysfunction in a novel model of prodromal Parkinson's disease in adult zebrafish
Olfactory dysfunction is a clinical marker of prodromal Parkinson\'s disease (PD), a neurodegenerative disorder characterized by severe motor impairments. Although common, the mechanisms linking PD and olfactory dysfunction remain unclear. To explore this relationship, we developed a model of olfactory dysfunction that recapitulates the prodromal stage of PD without affecting motor function. For t...
Vorhees, N. W.
•
Groenwold, S. L.
•
Williams, M. T.
•
Putt, L. S.
...•
Calvo-Ochoa, E.
biorxiv
Wed Apr 02 2025
On variability in local field potentials
Neuronal coding and decoding would be compromised if neuronal responses were highly variable. Intriguingly, neuronal spike counts (SCs) show a reduction in across-trial variance (ATV) in response to sensory stimulation, when SC variance is normalized by SC mean, that is, when using the Fano factor 1. Inspired by this seminal finding, ATV has also been studied in electroencephalography (EEG) signal...
Parto-Dezfouli, M.
•
Johnson, E. L.
•
Psarou, E.
•
Bosman, C. A.
...•
Fries, P.