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Pathological Mechanisms of Tendinopathy Pain: From Mechanical Overload to Neuroimmune-Vascular Crosstalk.

Created on 16 Sep 2026

Authors

Chenyu He, Aikang Li, Qingyi Liu, Mingyang Xu, Hongbo You, Hewei Li

Published in

Pain research & management. Volume 2026. Issue 1. Pages e1712265.

Abstract

Characterized by localized pain and functional impairment, tendinopathy remains a significant challenge in sports medicine. Traditional models of structural degeneration and inflammation inadequately explain the clinical discordance between tissue damage and pain severity. This review explores the paradigm shift in understanding tendinopathic pain, elucidating the transition from a simple mechanical stress model to a complex neuroplastic disorder. We narratively review the multilayered pathophysiological mechanisms underlying chronic tendinopathic pain. Specifically, we outline abnormal mechanical load transduction, peripheral neuroimmune-vascular coupling, and central nervous system (CNS) remodeling. Abnormal mechanical overload initially activates mechanosensitive ion channels, transducing physical stress into biochemical nociceptive signals. Subsequently, chronic immune responses and neurovascular coupling drive peripheral sensitization, which is further amplified by aberrant sensory neoinnervation and neuroimmune crosstalk. Furthermore, CNS involvement manifests as spinal-level central sensitization and maladaptive remodeling of the motor cortex. Managing chronic tendinopathic pain requires transcending the traditional focus on localized structural lesions. Future strategies should prioritize precise clinical phenotyping, targeted pharmacotherapy, and neuroplasticity-informed rehabilitation to optimize patient outcomes.

PMID:
42746970
Bibliographic data and abstract were imported from PubMed on 16 Sep 2026.

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