Biology subjects

Velasco, E.

Publications and source records attributed to Velasco, E..

3 recordsLinked to original sources

bioRxiv2026

Dynamic Responses to an Inflammatory Challenge Distinguish Metabolic Health Across Lean and Obese Individuals

Inflammation is a key driver of cardiometabolic disease, yet it remains unclear whether systemic inflammatory markers can distinguish metabolically healthy from unhealthy individuals or capture the temporal dynamics of inflammation. Here, we combined systemic immune profiling with a cantharidin-induced peripheral blister model to investigate dynamic inflammatory regulation across metabolic phenotypes in metabolically healthy lean (MHL), metabolically unhealthy lean (MUL), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) individuals. While systemic inflammation was elevated in obesity, differences between metabolically healthy and unhealthy groups were modest, with limited discrimination by plasma proteomics, circulating leukocyte phenotyping, and whole-blood transcriptomics. In contrast, the dynamic response to inflammatory challenge revealed pronounced differences at proteomic, cellular, and transcriptomic levels. Metabolically unhealthy individuals exhibited exaggerated early innate immune responses, impaired inflammatory resolution and tissue repair, reduced recruitment of reparative immune cells, and sustained T cell presence. Transcriptomic analyses further showed blunted dynamic gene regulation and defective epidermal barrier restoration. These findings indicate that metabolic health is better reflected in tissue-level inflammatory dynamics than in systemic measures.

immunology↗

bioRxiv2026

Tactile and pain mechanical sensitivity of the human hand

The human hand has a refined mechanical sensitivity, allowing it to play crucial roles in tactile exploration and object manipulation. Despite its fundamental and clinical relevance, a comprehensive characterization of mechanical sensitivity across the human palm is still lacking. Here, we mapped the spatial distribution of innocuous and noxious mechanical sensitivity across the palmar surface of the human hand. We examined 66 hands from 33 healthy adults, dividing the palm into 27 areas, in each of which we measured the mechanical detection threshold, the mechanical pain threshold and the pain intensity evoked by a standard 300 g pinprick stimulus. We found distal areas (i.e., fingertips) to exhibit higher tactile sensitivity than proximal areas (i.e., the wrist). Notably, the sensitivity to innocuous and noxious mechanical stimuli were inversely correlated across areas, such that areas with higher tactile sensitivity displayed higher pain thresholds. In addition, the dominant hand was less sensitive than the non-dominant one, and women displayed higher sensitivity than men. Together, this work provides the first detailed spatial characterization of mechanical sensitivity across the human hand and introduces a systematic methodology for its assessment. These findings set the stage for future studies of the neurophysiological mechanisms of touch and pain in the human hand and for clinical research into pathological conditions involving the altered hand sensitivity.

physiology↗

bioRxiv2024

Adaptation of pain-related projection neurons in acute but not chronic pain

Pain hypersensitivity is associated with increased activity of peripheral and central neurons along the pain neuroaxis1. On the other hand, in other neuronal systems, increased activity leads to adaptive reduction of neuronal excitability to maintain homeostasis2-4. Projection neurons (PNs) of spinal and medullary dorsal horns summate the activity of primary nociceptive and local central interneurons and convey it to higher centers5. We show that at the peak of acute inflammatory pain, PNs reduce their intrinsic excitability and, consequently, action potential firing. When pain resolves, the excitability of PNs returns to baseline. Using electrophysiological and computational approaches, we found that an increase in potassium A-current (IA) underlies the decrease in the excitability of PNs in acute pain conditions. We hypothesized that an IA-induced decrease in PNs firing may restrain the output from the dorsal horn to prevent sensitization and pain chronification. Indeed, no changes of IA in PNs were observed in chronic pain conditions, and PNs exhibit increased intrinsic excitability and firing. Our results reveal an adaptive mechanism in acute pain conditions for regulating the output from the dorsal horn network, which, if interrupted, could trigger pain chronification.

neuroscience↗