EXPLORING POTENTIAL TARGETS IN A MOUSE MODEL OF COMPLEX REGIONAL PAIN SYNDROME BY SPATIAL TRANSCRIPTOMIC ANALYSIS

CRPS is a chronic primary pain disorder characterized by persistent, severe unilateral limb pain, edema, and autonomic dysfunction. Diseases in this category are associated with long-term, persistent pain that develops without a clear cause and is often accompanied by CNS comorbidities, reduced quality of life, representing a significant medical and socio-economic burden. As current therapeutic options are still unsatisfactory, it is essential to investigate the underlying pathophysiological processes, identify new pharmacological targets using translational animal models incorporating integrated testing techniques.
We developed a passive transfer trauma mouse model in which intraperitoneal administration of purified immunoglobulin G fractions from CRPS patients, combined with plantar skin-muscle incision mimicking tissue trauma, successfully reproduced the most characteristic symptoms of CRPS in mice, confirming the autoimmune nature of the disease. Spatial transcriptomics was applied to investigate molecular and pathway-level mechanisms underlying the development and maintenance of chronic pain. Gene expression changes were profiled across multiple levels of the pain-processing system, including primary and secondary sensory neurons, as well as ascending nociceptive and descending inhibitory pathways using Visium CytAssist platform. Analysis of spinal cord samples revealed that administration of human CRPS-IgG induces pronounced transcriptional alterations associated with pain signaling and neuroinflammation such as the activation of interleukin- and cytokine storm–related pathways, along with macrophage-, chemokine receptor–, and eicosanoid (prostaglandin)-mediated signaling, was observed, suggesting a central role for immune–neuronal interactions in CRPS pathophysiology. These findings highlight coordinated inflammatory and nociceptive network activation at the spinal level.
NAP 3.0, NKFIH FK 146283, K-138046; TKP2021-EGA-16, RRF-2.3.1-21-2022-00015