Hyperalgesia is an increased pain response to stimuli that are normally painful — the gain on pain is turned up, so that a mildly painful stimulus produces severe pain. Unlike allodynia (pain from non-painful stimuli), hyperalgesia involves stimuli that would produce some pain in anyone; the difference is in the magnitude of the response.
Hyperalgesia is classified by location relative to the original injury:
- Primary hyperalgesia — increased pain sensitivity at the site of tissue damage. This is partly driven by peripheral sensitization: inflammatory mediators lower nociceptor thresholds, so nerve fibers in the injured area fire more readily. The inflamed area around a cut or burn being exquisitely tender to touch is primary hyperalgesia.
- Secondary hyperalgesia — increased pain sensitivity in uninjured tissue surrounding the site of damage. This is driven by central sensitization: the spinal cord amplifies signals from the broader region, not just from the injury site. The area around a burn being painful to light pressure, even where the skin is intact, is secondary hyperalgesia.
The clinical distinction matters. Primary hyperalgesia may respond to anti-inflammatory treatment targeting the peripheral sensitization. Secondary hyperalgesia will not — because the amplification is occurring centrally.
Opioid-induced hyperalgesia
A particularly significant form is opioid-induced hyperalgesia (OIH) — a paradoxical state in which opioid use itself increases pain sensitivity. Rather than producing more analgesia, continued opioid exposure activates pronociceptive mechanisms (NMDA receptor activation, glial activation, descending facilitation) that amplify pain. The patient reports worsening pain, the clinician increases the opioid dose, the hyperalgesia worsens, the dose increases again — a cycle that can produce severe, widespread pain driven entirely by the treatment intended to relieve it.
OIH is clinically distinct from tolerance (which requires more drug to achieve the same effect) and from disease progression (which involves worsening of the underlying condition). It is one of the mechanisms through which the opioid crisis has harmed chronic pain patients — patients whose pain worsened precisely because of the medications prescribed to manage it, then faced dose reductions that produced withdrawal on top of iatrogenic hyperalgesia.
This dynamic connects directly to harm reduction. Patients experiencing OIH need careful, compassionate dose management — not abrupt discontinuation (which produces withdrawal and rebound pain) and not dose escalation (which worsens the hyperalgesia). The harm reduction principle of meeting people where they are, reducing immediate danger, and treating survival as the first priority applies directly to opioid taper in hyperalgesic patients.
Related terms
- Allodynia — pain from non-painful stimuli (the companion concept)
- Central Sensitization — the mechanism driving secondary hyperalgesia
- Nociception — the peripheral process that hyperalgesia amplifies
- Chronic Pain — the condition in which hyperalgesia is commonly observed