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Hyperalgesia - Wikipedia, the free encyclopedia

10/05/15 18:05

From Wikipedia, the free encyclopedia

Hyperalgesia (/haprldizi/ or /-si/; 'hyper'

from Greek (huper, over), '-algesia' from
Greek algos, (pain)) is an increased
sensitivity to pain, which may be caused by
damage to nociceptors or peripheral nerves.
Temporary increased sensitivity to pain also occurs
as part of sickness behavior, the evolved response
to infection.[1]

Classification and external resources


DiseasesDB 30788



1 Types
2 Causes
3 Treatment
4 See also
5 References

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.[2]
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.

Hyperalgesia is induced by platelet-activating factor (PAF) which comes about in an inflammatory or an allergic
response. This seems to occur via immune cells interacting with the peripheral nervous system and releasing
pain-producing chemicals (cytokines and chemokines).[3]

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One unusual cause of focal hyperalgesia is platypus venom.[4]

Long term opioid (e.g. heroin, morphine) 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.[2][5][6] 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,[7][8][9] and blocking
this receptor may therefore be a means of preventing the development of hyperalgesia.[10]
Stimulation of nociceptive fibers in a pattern consistent with that from inflammation switches on a form of
amplification in the spinal cord, long term potentiation.[11] This occurs where the pain fibres synapse to pain
pathway, the periaqueductal grey. Amplification in the spinal cord may be another way of producing
The release of proinflammatory cytokines such as Interleukin-1 by activated leukocytes triggered by
lipopolysaccharides, endotoxins and other signals of infection also increases pain sensitivity as part of sickness
behavior, the evolved response to illness.[1][12][13]

Hyperalgesia is similar to other sorts of pain associated with nerve
irritation or damage such as allodynia and neuropathic pain, and
consequently may respond to standard treatment for these conditions,

Look up hyperalgesia in
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using various drugs such as SSRI or tricyclic antidepressants,[14][15]

Non-steroidal anti-inflammatory drugs,[16] glucocorticoids,[17] gabapentin[18] or pregabalin,[19] NMDA
antagonists,[20][21][22] or atypical opioids such as tramadol.[23] Where hyperalgesia has been produced by
chronic high doses of opioids, reducing the dose may result in improved pain management.[24] 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. The use of a transcutaneous electrical nerve stimulation device has been shown to alleviate

See also


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1. Hart BL (1988). "Biological basis of the behavior of sick animals" ( Neurosci Biobehav Rev 12 (2): 12337. doi:10.1016/S0149-7634(88)80004-6
( PMID 3050629
2. Chu LF, Angst MS, Clark D (2008). "Opioid-induced hyperalgesia in humans: molecular mechanisms and clinical
considerations" ( Clin J Pain 24 (6): 47996. doi:10.1097/AJP.0b013e31816b2f43
( PMID 18574358
3. Marchand F, Perretti M, McMahon SB (July 2005). "Role of the immune system in chronic pain". Nat. Rev. Neurosci. 6
(7): 52132. doi:10.1038/nrn1700 ( PMID 15995723
4. de Plater GM, Milburn PJ, Martin RL (March 2001). "Venom from the platypus, Ornithorhynchus anatinus, induces a
calcium-dependent current in cultured dorsal root ganglion cells" (
view=long&pmid=11248005). J. Neurophysiol. 85 (3): 13405. PMID 11248005
5. DuPen A, Shen D, Ersek M (September 2007). "Mechanisms of opioid-induced tolerance and hyperalgesia"
( Pain Manag Nurs 8 (3): 11321.
doi:10.1016/j.pmn.2007.02.004 ( PMID 17723928
6. Mitra S (2008). "Opioid-induced hyperalgesia: pathophysiology and clinical implications". J Opioid Manag 4 (3): 123
30. PMID 18717507 (
7. Okuda-Ashitaka E, Minami T, Matsumura S et al. (February 2006). "The opioid peptide nociceptin/orphanin FQ
mediates prostaglandin E2-induced allodynia, tactile pain associated with nerve injury"
( Eur. J. Neurosci. 23 (4): 9951004. doi:10.1111/j.14609568.2006.04623.x ( PMID 16519664
8. Fu X, Zhu ZH, Wang YQ, Wu GC (January 2007). "Regulation of proinflammatory cytokines gene expression by
nociceptin/orphanin FQ in the spinal cord and the cultured astrocytes" ( Neuroscience 144 (1): 27585. doi:10.1016/j.neuroscience.2006.09.016
( PMID 17069983
9. 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 ( PMID 17387690
10. Tamai H, Sawamura S, Takeda K, Orii R, Hanaoka K (March 2005). "Anti-allodynic and anti-hyperalgesic effects of
nociceptin receptor antagonist, JTC-801, in rats after spinal nerve injury and inflammation"
( Eur. J. Pharmacol. 510 (3): 2238.
doi:10.1016/j.ejphar.2005.01.033 ( PMID 15763246
11. Ikeda H, Stark J, Fischer H et al. (June 2006). "Synaptic amplifier of inflammatory pain in the spinal dorsal horn"
( Science 312 (5780): 165962.
doi:10.1126/science.1127233 ( PMID 16778058
12. Kelley KW, Bluth RM, Dantzer R et al. (February 2003). "Cytokine-induced sickness behavior"
( Brain Behav. 17 (Suppl 1): S1128.
doi:10.1016/S0889-1591(02)00077-6 ( PMID 12615196

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13. Maier SF, Wiertelak EP, Martin D, Watkins LR (October 1993). "Interleukin-1 mediates the behavioral hyperalgesia
produced by lithium chloride and endotoxin" ( Brain
Res. 623 (2): 3214. doi:10.1016/0006-8993(93)91446-Y ( PMID 8221116 (
14. Sindrup SH, Otto M, Finnerup NB, Jensen TS (June 2005). "Antidepressants in the treatment of neuropathic pain"
( Basic Clin. Pharmacol. Toxicol. 96 (6): 399409.
doi:10.1111/j.1742-7843.2005.pto_96696601.x (
PMID 15910402 (
15. 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". Neuropsychopharmacology
33 (8): 195265. doi:10.1038/sj.npp.1301590 ( PMID 17957217
16. Koppert W, Wehrfritz A, Krber N et al. (March 2004). "The cyclooxygenase isozyme inhibitors parecoxib and
paracetamol reduce central hyperalgesia in humans" (
Pain 108 (12): 14853. doi:10.1016/j.pain.2003.12.017 (
PMID 15109518 (
17. 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 Scand 51 (9): 113846.
doi:10.1111/j.1399-6576.2007.01415.x ( PMID 17714578
18. Gottrup H, Juhl G, Kristensen AD et al. (December 2004). "Chronic oral Gabapentin reduces elements of central
sensitization in human experimental Hyperalgesia." ( Anesthesiology
101 (6): 14008. doi:10.1097/00000542-200412000-00021 ( PMID 15564948 (
19. Chizh BA, Ghring M, Trster A, Quartey GK, Schmelz M, Koppert W (February 2007). "Effects of oral pregabalin and
aprepitant on pain and central sensitization in the electrical hyperalgesia model in human volunteers"
( Br J Anaesth 98 (2): 24654.
doi:10.1093/bja/ael344 ( PMID 17251214
20. Warncke T, Stubhaug A, Jrum 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.". Pain 72 (12): 99106. doi:10.1016/S0304-3959(97)00006-7
( PMID 9272793
21. 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 Anaesthesiol 21 (1): 8598. doi:10.1016/j.bpa.2006.12.006
( PMID 17489221 (
22. Klein T, Magerl W, Hanschmann A, Althaus M, Treede RD (January 2008). "Antihyperalgesic and analgesic properties
of the N-methyl-D-aspartate (NMDA) receptor antagonist neramexane in a human surrogate model of neurogenic
Hyperalgesia." ( Eur J Pain 12 (1): 1729.
doi:10.1016/j.ejpain.2007.02.002 ( PMID 17449306
23. Christoph T, Kgel B, Strassburger W, Schug SA (2007). "Tramadol has a better potency ratio relative to morphine in
neuropathic than in nociceptive pain models". Drugs R D 8 (1): 517. doi:10.2165/00126839-200708010-00005
( PMID 17249849

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24. Vorobeychik Y, Chen L, Bush MC, Mao J (September 2008). "Improved opioid analgesic effect following opioid dose
reduction." ( Pain Med 9 (6): 7247. doi:10.1111/j.1526-4637.2008.00501.x
( PMID 18816332
25. DeSantana, JM; Walsh, DM; Vance, C; Rakel, BA; Sluka, KA (December 2008). "Effectiveness of transcutaneous
electrical nerve stimulation for treatment of hyperalgesia and pain."
( Current rheumatology reports 10 (6): 4929.
PMC 2746624 ( PMID 19007541
26. Sluka, KA; Chandran, P (November 2002). "Enhanced reduction in hyperalgesia by combined administration of
clonidine and TENS.". Pain 100 (1-2): 18390. PMID 12435471 (

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