Chronic Stress Induces Neuroimmune Modulated Primary Muscle Afferent Sensitization

This research investigates mechanisms by which stress and neuroimmune interactions drive the transition from acute to chronic muscle pain. The program centers on primary muscle afferents — sensory neurons that mediate both nociception and cardiovascular reflexes — and on the non-neuronal cells that modulate their function. This current NIH-funded projects focus specifically on the role of macrophages in the development of long-lasting muscle pain, using a multidisciplinary approach that integrates molecular biology, ex vivo electrophysiology, and AI-driven behavioral analysis.

The central question of this project seeks to understand how neuroimmune interactions, especially involving macrophages, and stress-related processes produce long-lasting sensitization of primary muscle afferents and thereby sustain chronic muscle pain. Methodologically, the research leverages ex vivo preparations that permit electrophysiological recordings from muscle-nerve-dorsal root ganglion-spinal cord circuits, enabling precise mechanistic analyses of afferent function following manipulations. Molecular biology techniques are employed to profile signaling changes and cell–cell communication within muscle tissue and sensory ganglia. Complementing these approaches, AI-driven behavioral analysis allows quantitative, high-throughput assessment of changes in voluntary activity and pain-related behaviors in animal models, linking cellular and molecular findings to functional outcomes.

The program’s focus on non-neuronal regulation of pain emphasizes interactions between immune cells and sensory neurons that can be modulated by physiological stressors. This research aims to define peripheral targets and pathways that could be manipulated to prevent the transition from acute to chronic muscle pain, elucidate how stress exacerbates or sustains afferent sensitization  and identify biomarkers or behavioral signatures associated with neuroimmune-modulated pain states. The lab combines interdisciplinary expertise to advance understanding of musculoskeletal pain mechanisms and to translate those insights toward improved diagnosis and treatment strategies for chronic muscle pain.