Small-fiber degeneration, sensory dysfunction, and nociception comorbidity in central neurodegenerative disease
Year: 2026
Type: review
Abstract: Progressive neurodegenerative disease typically calls for clinical effort to improve cognitive and motor deficits. It is also focused on improving patients' quality of life. However, across these dementias and other diseases, the underlying causes and potential mechanisms remain unclear. Most experimental and clinical research focuses on the central nervous system, examining pathogenic proteins such as tau and amyloid beta, as well as the potential cascade following mitochondrial damage and neuroinflammation. Although peripheral involvement, including gut microbiome influences and other visceral organs, is well-documented, the peripheral nervous system remains an understudied component of these progressive diseases. As peripheral terminals of primary afferent neurons are exposed to inflammatory or toxic mediators, these neurons respond to these threats via neuron-specific phenotypic changes, including the generation of pain. Although normal peripheral sensitization is protective, exposure to damage in a chronic disease state can have long-term detrimental effects. Diseases that lead to central neurodegeneration often also feature peripheral neuropathy and chronic pain. We provide an overview of the incidence of peripheral neuropathy within these diseases, the contribution of changes in sensation to disease, and secondary neuropathic phenotypes resulting from disease. Woven in are discussions of the intersection of degeneration and toxic protein aggregation, briefly touching on resulting inflammatory signaling. Altogether, this review aims to synthesize current understanding of sensory peripheral nerve involvement across these neurodegenerative diseases.
Source: Frontiers in Aging Neuroscience
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223175972