hyperalgesia

Hyperalgesia is an increased sensitivity to pain, in which a noxious stimulus evokes greater pain than would normally be expected. It can occur at the site of tissue injury (primary hyperalgesia) or in surrounding, uninjured tissue (secondary hyperalgesia).

Primary hyperalgesia results from peripheral sensitization of nociceptors due to inflammatory mediators such as prostaglandins, bradykinin, cytokines, and nerve growth factor. This lowers activation thresholds and increases nociceptor excitability. Secondary hyperalgesia reflects central sensitization: enhanced function of central nociceptive pathways, wind-up and hyperexcitability of dorsal horn neurons, diminished inhibitory controls, and spread of sensitization within the CNS.

Hyperalgesia arises after tissue injury or infection, in inflammatory conditions, neuropathic disorders, postoperative states, cancer, chemotherapy-induced neuropathy, and conditions such as complex regional pain syndrome and fibromyalgia. Opioid-induced hyperalgesia refers to paradoxical pain sensitization during opioid therapy, related to central sensitization; it is conceptually distinct from tolerance.

Diagnosis is clinical; quantitative sensory testing may aid assessment in research and specialist settings. Treatment targets the underlying cause and may include anti-inflammatory drugs, anticonvulsants, antidepressants for neuropathic pain, topical agents, and nonpharmacologic methods. In some situations, careful opioid management and strategies to minimize opioid-induced hyperalgesia are advised. Early control of inflammation and pain after injury can reduce hyperalgesic responses.