Pronociception

Pronociception refers to neural and physiological processes that enhance nociceptive signaling and pain perception. It describes a state in which the nervous system is inclined to amplify pain, often counteracting analgesic or antinociceptive mechanisms. Pronociception can operate at peripheral, spinal, and supraspinal levels, contributing to heightened pain responses such as dynamic hyperalgesia and allodynia, as well as context- or state-dependent amplification of pain.

Mechanisms underlying pronociception include peripheral sensitization, where inflammatory mediators like prostaglandins, bradykinin, cytokines, and nerve growth factor decrease nociceptor thresholds; spinal sensitization and wind-up in the dorsal horn that increase excitability; and central sensitization involving NMDA receptor–dependent long-term changes that amplify pain signaling. Descending facilitation from brainstem regions, such as the rostral ventromedial medulla and other parts of the pain modulatory system, can further enhance nociceptive transmission. Neurotransmitters and peptides such as glutamate, substance P, and CGRP participate in these processes, while stress-related systems can shift the balance toward pronociception.

Clinical and research relevance centers on chronic pain and conditions with amplified pain sensitivity, including fibromyalgia and certain temporomandibular disorders. Pronociceptive processes help explain why pain can persist after tissue healing and why some individuals experience disproportionate pain. Therapeutic approaches often aim to reduce facilitation (for example, NMDA receptor antagonists, certain anticonvulsants, and antidepressants that modulate descending pathways) and to address contributing psychological and inflammatory factors.