Hyperalgesia can be experienced in focal, discrete areas, or as a more diffuse, body-wide form. Conditioning studies have established that it is possible to experience a learned hyperalgesia of the latter, diffuse form.
The focal form is typically associated with injury, and is divided into two subtypes:
Primary hyperalgesia describes pain sensitivity that occurs directly in the damaged tissues.
Secondary hyperalgesia describes pain sensitivity that occurs in surrounding undamaged tissues.
Opioid-induced hyperalgesia may develop as a result of long-term opioid use in the treatment of chronic pain. Various studies of humans and animals have demonstrated that primary or secondary hyperalgesia can develop in response to both chronic and acute exposure to opioids This side effect can be severe enough to warrant discontinuation of opioid treatment.
Long term opioid (e.g. heroin, oxycodone) users and those on high-dose opioid medications for the treatment of chronic pain, may experience hyperalgesia and experience pain out of proportion to physical findings, which is a common cause for loss of efficacy of these medications over time. As it can be difficult to distinguish from tolerance, opioid-induced hyperalgesia is often compensated for by escalating the dose of opioid, potentially worsening the problem by further increasing sensitivity to pain. Chronic hyperstimulation of opioid receptors results in altered homeostasis of pain signalling pathways in the body with several mechanisms of action involved. One major pathway being through stimulation of the nociceptin receptor, and blocking this receptor may therefore be a means of preventing the development of hyperalgesia.
Hyperalgesia is similar to other sorts of pain associated with nerve damage such as allodynia and neuropathic pain, and consequently may respond to standard treatment for these conditions, using various drugs such as SSRI or tricyclic antidepressants, non-steroid antiinflammatory drugs,glucocorticoids,gabapentin or pregabalin,NMDA antagonists, or atypical opioids such as tramadol. Where hyperalgesia has been produced by chronic high doses of opioids, reducing the dose may result in improved pain management. However, as with other forms of nerve dysfunction associated pain, treatment of hyperalgesia can be clinically challenging, and finding a suitable drug or drug combination that is effective for a particular patient may require trial and error.
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