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.
^Chen Y, Sommer C (May 2007). "Activation of the nociceptin opioid system in rats. Sensory neurons produce antinociceptive effects in inflammatory pain: involvement of inflammatory mediators". J. Neurosci. Res.85 (7): 1478–88. doi:10.1002/jnr.21272. PMID17387690.
^Matsuzawa-Yanagida K, Narita M, Nakajima M, et al. (July 2008). "Usefulness of antidepressants for improving the neuropathic pain-like state and pain-induced anxiety through actions at different brain sites". Neuropsychopharmacology33 (8): 1952–65. doi:10.1038/sj.npp.1301590. PMID17957217.
^Stubhaug A, Romundstad L, Kaasa T, Breivik H (October 2007). "Methylprednisolone and Ketorolac rapidly reduce hyperalgesia around a skin burn injury and increase pressure pain thresholds". Acta Anaesthesiol Scand51 (9): 1138–46. doi:10.1111/j.1399-6576.2007.01415.x. PMID17714578.
^Warncke T, Stubhaug A, Jørum E (August 1997). "Ketamine, an NMDA receptor antagonist, suppresses spatial and temporal properties of burn-induced secondary Hyperalgesia in man: a double-blind, cross-over comparison with morphine and placebo.". Pain72 (1–2): 99–106. doi:10.1016/S0304-3959(97)00006-7. PMID9272793.
^De Kock MF, Lavand'homme PM (March 2007). "The clinical role of NMDA receptor antagonists for the treatment of postoperative pain". Best Pract Res Clin Anaesthesiol21 (1): 85–98. doi:10.1016/j.bpa.2006.12.006. PMID17489221.