crosssensitization

Cross-sensitization is a phenomenon in which sensitization or heightened responsiveness to stimuli in one tissue or organ leads to an increased response to stimuli in another, often related, tissue. It is frequently discussed in pain research, where repeated or ongoing stimulation in one region can enhance sensitivity in distant or functionally connected areas. The effect is thought to involve changes in the central nervous system, peripheral inflammatory signaling, and neural plasticity.

The mechanisms underlying cross-sensitization include peripheral sensitization that influences central circuits, convergence of nociceptive inputs in the spinal dorsal horn, and the activation of glial cells that release pro-inflammatory cytokines and neuromodulators such as substance P, calcitonin gene-related peptide, and glutamate. These processes can lower pain thresholds in non-injured tissues and promote widespread or bilateral hyperexcitability. Central sensitization, altered descending modulation, and persistent inflammatory signaling are commonly implicated.

Cross-sensitization can be categorized as somatic-somatic (injury or inflammation in one somatic region increasing sensitivity in another), viscerosomatic (visceral organ input contributing to somatic pain), and viscerovisceral (dysfunction in one organ affecting sensitivity in another). In humans, conditions such as temporomandibular joint disorders with neck or shoulder pain, and some functional disorders like irritable bowel syndrome with pelvic or urinary symptoms, are discussed as potential examples. Animal studies have demonstrated cross-sensitization after tissue injury, supporting shared central pathways.

Clinically, cross-sensitization can complicate the assessment and management of chronic pain, contributing to diffuse pain, bilateral symptoms, and comorbidity across organ systems. Management typically emphasizes multimodal strategies aimed at reducing central nervous system hyperexcitability and peripheral inflammation, including physical therapy, pharmacologic analgesia, and interventions targeting neural plasticity.