Advanced cancer perineural invasion induces profound peripheral neuronal plasticity, pain, and somatosensory mechanical deactivation, unmitigated by the lack of TNFR1. Part. 1: Behavior and single-cell in vivo electrophysiology

• Published in: Molecular pain Vol. 21; p. 17448069251314738
• Main Authors: Gutierrez, Silvia, Parker, Renee A, Zhang, Morgan, Santi, Maria Daniela, Ye, Yi, Boada, M Danilo
• Format: Journal Article
• Language: English
• Published: United States SAGE Publications 01.01.2025
• Subjects: Animals; Behavior, Animal; Female; Ganglia, Spinal - metabolism; Ganglia, Spinal - pathology; Ganglia, Spinal - physiopathology; Hyperalgesia - pathology; Hyperalgesia - physiopathology; Male; Mice; Mice, Inbred C57BL; Neoplasm Invasiveness; Neuronal Plasticity - physiology; Pain - pathology; Pain - physiopathology; Receptors, Tumor Necrosis Factor, Type I - deficiency; Receptors, Tumor Necrosis Factor, Type I - metabolism; Sciatic Nerve - pathology; Sciatic Nerve - physiopathology; nociception; pain; PNI; somatosensory system; MOC2; Cancer
• DOI: 10.1177/17448069251314738
• ISSN: 1744-8069

Patients with cancer perineural invasion (PNI) report greater spontaneous pain and mechanical allodynia. Here, we examine the impact of the disease on the peripheral sensory system, the excitability changes induced by PNI at the dorsal root ganglia, and the potential protective role of the absence of Tumor Necrosis Factor-α Receptor 1 (TNFR1). To study these effects, we use a murine model generated by injecting mouse oral cancer squamous cell carcinoma (MOC2) into the sciatic nerve (MOC2-PNI) in both male and female mice. We found that MOC2-PNI induces a profound change in the somatosensory landscape by deactivating/blocking the peripheral inputs while modulating the afferent’s sensibility (tactile desensitization with concurrent nociceptive sensitization) and demyelination without inducing spontaneous activity. All these changes caused by MOC2-PNI are unmitigated by the absence of TNFR1. We conclude that MOC2-PNI induces an aberrant neuronal excitability state and triggers extreme gender-specific neuronal plasticity. These data allow us to speculate on the role of such plasticity as a powerful defense mechanism to prevent terminal sensory dysfunction, the rise of chronic pain, and extend animals’ survivability.