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Updated: Sep 5, 2025

Multi-Modal Signals for Analyzing Pain Responses to Thermal and Electrical Stimuli
Published on: April 5, 2019
Concepts of Entheseal Pain
Enrico De Lorenzis1, Gerlando Natalello1, David Simon2
1Division of Rheumatology, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Abstract:
Pain is the main symptom in entheseal diseases (enthesopathies) despite a paucity of nerve endings in the enthesis itself. Eicosanoids, cytokines, and neuropeptides released during inflammation and repeated nonphysiologic mechanical challenge not only stimulate or sensitize primary afferent neurons present in structures adjacent to the enthesis, but also trigger a "neurovascular invasion" that allows the spreading of nerves and blood vessels into the enthesis. Nociceptive pseudounipolar neurons support this process by releasing neurotransmitters from peripheral endings that induce neovascularization and peripheral pain sensitization. This process may explain the frequently observed dissociation between subjective symptoms such as pain and the structural findings on imaging in entheseal disease.
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