Biology subjects

Solinski, H. J.

Publications and source records attributed to Solinski, H. J..

3 recordsLinked to original sources

bioRxiv2026

Direct sensitizing and activating effects of interleukin 31 are restricted to a single, functionally and transcriptionally classified porcine DRG neuron subtype.

Interleukin-31 (IL-31) drives chronic pruritus in patients with dermatological and even certain systemic diseases. However, fast-onset anti-pruritic effects of blocking IL-31 receptors, for instance with nemolizumab in atopic dermatitis patients, are incompletely understood, in part due to ethical restrictions in humans and species differences to mice. Therefore, we used sensory neuron cultures from pig to investigate direct neuronal IL-31 effects. We first mapped functional characteristics of afferents encoding histamine itch in humans onto a recently established transcriptome-based DRG neuron taxonomy to identify pig pruriceptors. IL-31 acutely sensitized responses to repeated pruritogen and electrical stimulation only in these histamine- and capsaicin-responsive pruriceptors and also activated these afferents with silent nociceptor phenotype in vivo as validated by dermal axon-reflex erythema measurements. Thus, our data functionally and transcriptionally identifies the likely sensory neuron class underlying IL-31-driven chronic pruritus and opens a perspective for translational research on distinct neuronal classes differentially driving skin inflammation and clinical chronic pruritus via specific neuro-immune signaling patterns.

neuroscience↗

bioRxiv2024

Molecular architecture of human dermal sleeping nociceptors

Human dermal sleeping nociceptors display ongoing activity in neuropathic pain, affecting 10% of the population. Despite advances in rodents, a molecular marker for these mechano-insensitive C-fibers (CMis) in human skin remains elusive, preventing targeted therapy. In this translational Patch-seq study, we combine single-cell transcriptomics following electrophysiological characterization with single-nucleus and spatial transcriptomics from pigs and humans. We functionally identified CMis in pig sensory neurons with patch-clamp using adapted protocols from human microneurography. We identified oncostatin-M-receptor (OSMR) and somatostatin (SST) as marker genes for CMis. Following dermal injection in healthy human volunteers, oncostatin-M, the ligand of OSMR, exclusively modulates CMis. We identified the entire molecular architecture of human dermal sleeping nociceptors, providing new therapeutic targets and the basis for a mechanistic understanding of neuropathic pain. One Sentence SummaryWe identify the molecular architecture and specifically OSMR and SST as molecular markers for human dermal sleeping nociceptors, key players in the generation of neuropathic pain. Short versionIn this Patch-seq study, we identify OSMR and SST as molecular markers for human dermal sleeping nociceptors, key players in the generation of neuropathic pain.

neuroscience↗

bioRxiv2020

Pruriception and neuronal coding in nociceptor subtypes in human and nonhuman primates

In human, intradermal administration of {beta}-alanine (ALA) and bovine adrenal medulla peptide 8-22 (BAM8-22) evokes the sensation of itch. Currently, it is unknown which human dorsal root ganglion (DRG) neurons express the receptors of these pruritogens, MRGPRD and MRGPRX1 respectively, and which cutaneous afferents these pruritogens activate in primate. In situ hybridization studies revealed that MRGPRD and MRGPRX1 are co-expressed in a subpopulation of TRPV1+ human DRG neurons. In electrophysiological recordings in nonhuman primates (Macaca nemestrina), subtypes of polymodal C-fiber nociceptors are preferentially activated by ALA and BAM8-22, with significant overlap. When pruritogens ALA, BAM8-22 and histamine, that activate different subclasses of C-fiber afferents, are administered in combination, human volunteers report itch and nociceptive sensations similar to those induced by a single pruritogen. Our results provide evidence for differences in pruriceptive processing between primates and rodents, and do not support the spatial contrast theory of coding of itch and pain.

neuroscience↗