Pain

Disease / Phenomenon

Pain is the body's protective signaling system, an unpleasant sensory and emotional experience associated with actual or threatened tissue damage. Acute pain serves a clear purpose, prompting withdrawal and rest while healing proceeds. Chronic pain, defined as persisting beyond three months, is different in kind rather than degree: the nervous system itself becomes altered, and pain continues after the original injury has resolved or without any identifiable damage at all. Clinicians distinguish nociceptive pain from tissue injury, neuropathic pain from nerve damage, and nociplastic pain from altered central processing, as in fibromyalgia. Chronic pain affects a large share of adults and carries substantial effects on sleep, mood, and function.

Transduction begins at peripheral nociceptors, where TRPV1, TRPA1, and voltage-gated sodium channels including Nav1.7 and Nav1.8 convert noxious stimuli into electrical signals. Inflammatory mediators — prostaglandin E2 produced via COX-2, bradykinin, nerve growth factor, IL-1beta, and TNF-alpha — lower activation thresholds, producing peripheral sensitization. In the dorsal horn, glutamate acting on NMDA receptors, substance P, and activated microglia and astrocytes drive central sensitization and wind-up. Descending modulation through opioid, serotonergic, noradrenergic, and endocannabinoid systems can amplify or dampen the signal. This page organizes these processes into pathways and biomarkers.