Allodynia and hyperalgesia: review

  • K. D. Dmytriiev National Pirogov Memorial Medical University, Vinnytsya
  • O. V. Marchuk National Pirogov Memorial Medical University, Vinnytsya
  • K. D. Dmytriiev National Pirogov Memorial Medical University, Vinnytsya
Keywords: hyperalgesia, allodynia, treatment, prevention, pathologic


The main purpose was to highlight the problem of hyperalgesia and allodynia. Main anatomic structures, which participate in nociception were mentioned in this article, with pathologic and pathophysiologic changes, that can be caused by hyperalgesia and allodynia. Main methods of diagnostics and assessment of mentioned symptoms were represented along with the modern approaches to treatment and prevention.


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Lolignier S, Eijkelkamp N, Wood JN. Mechanical allodynia. Pflügers Archiv - European Journal of Physiology [Internet]. Springer Nature; 2014 May 22;467(1):133–9. Available from:

Sandkühler J. Models and Mechanisms of Hyperalgesia and Allodynia. Physiological Reviews [Internet]. American Physiological Society; 2009 Apr;89(2):707–58. Available from:

Hardy JD, Wolff HG, Goodell H. Experimental evidence on the nature of cutaneous hyperalgesia. Journal of Clinical Investigation [Internet]. American Society for Clinical Investigation; 1950 Jan 1;29(1):115–40. Available from:

Meyer R, Ringkamp M, Campbell JN, Raja SN. Neural mechanisms of hyperalgesia after tissue injury. Johns Hopkins APL Technical Digest (Applied Physics Laboratory). 2005 Jan;26(1):56-66.

Ali Z, Meyer AR, Campbell NJ. Secondary hyperalgesia to mechanical but not heat stimuli following a capsaicin injection in hairy skin. Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 1996 Dec;68(2):401–11. Available from:

RAJA SN, CAMPBELL JN, MEYER RA. Evidence for different mechanisms of primary and secondary hyperalgesia following heat injury to the glabrous skin. Brain [Internet]. Oxford University Press (OUP); 1984;107(4):1179–88. Available from:

Minami T, Okuda-Ashitaka E, Hori Y, Sakuma S, Sugimoto T, Sakimura K, et al. Involvement of primary afferent C-fibres in touch-evoked pain (allodynia) induced by prostaglandin E2. European Journal of Neuroscience [Internet]. Wiley; 1999 Jun;11(6):1849–56. Available from:

Kehl LJ, Trempe TM, Hargreaves KM. A new animal model for assessing mechanisms and management of muscle hyperalgesia. Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 2000 Apr;85(3):333–43. Available from:

Tarpley JW, Kohler MG, Martin WJ. The behavioral and neuroanatomical effects of IB4-saporin treatment in rat models of nociceptive and neuropathic pain. Brain Research [Internet]. Elsevier BV; 2004 Dec;1029(1):65–76. Available from:

MAIER SF, GOEHLER LE, FLESHNER M, WATKINS LR. The Role of the Vagus Nerve in Cytokine-to-Brain Communication. Annals of the New York Academy of Sciences [Internet]. Wiley; 1998 May;840(1):289–300. Available from:

Vera-Portocarrero LP, Zhang E-T, King T, Ossipov MH, Vanderah TW, Lai J, et al. Spinal NK-1 receptor expressing neurons mediate opioid-induced hyperalgesia and antinociceptive tolerance via activation of descending pathways. Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 2007 May;129(1):35–45. Available from:

Shan S, Hong C, Mei H, Ting-Ting L, Hai-Li P, Zhi-Qi Z, et al. New evidence for the involvement of spinal fractalkine receptor in pain facilitation and spinal glial activation in rat model of monoarthritis. Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 2007 May;129(1):64–75. Available from:

Zhuang Z-Y. A Peptide c-Jun N-Terminal Kinase (JNK) Inhibitor Blocks Mechanical Allodynia after Spinal Nerve Ligation: Respective Roles of JNK Activation in Primary Sensory Neurons and Spinal Astrocytes for Neuropathic Pain Development and Maintenance. Journal of Neuroscience [Internet]. Society for Neuroscience; 2006 Mar 29;26(13):3551–60. Available from:

Saadé N., Baliki M, El-Khoury C, Hawwa N, Atweh S., Apkarian A., et al. The role of the dorsal columns in neuropathic behavior: evidence for plasticity and non-specificity. Neuroscience [Internet]. Elsevier BV; 2002 Dec;115(2):403–13. Available from:

Palecek J, Paleckova V, Willis WD. The roles of pathways in the spinal cord lateral and dorsal funiculi in signaling nociceptive somatic and visceral stimuli in rats. Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 2002 Apr;96(3):297–307. Available from:

Giller CA. The Neurosurgical Treatment of Pain. Archives of Neurology [Internet]. American Medical Association (AMA); 2003 Nov 1;60(11):1537. Available from:

Sanoja R, Vanegas H, Tortorici V. Critical Role of the Rostral Ventromedial Medulla in Early Spinal Events Leading to Chronic Constriction Injury Neuropathy in Rats. The Journal of Pain [Internet]. Elsevier BV; 2008 Jun;9(6):532–42. Available from:

Wei F, Dubner R, Ren K. Nucleus reticularis gigantocellularis and nucleus raphe magnus in the brain stem exert opposite effects on behavioral hyperalgesia and spinal Fos protein expression after peripheral inflammation. Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 1999 Mar;80(1):127–41. Available from:

Zhao P, Waxman SG, Hains BC. Modulation of Thalamic Nociceptive Processing after Spinal Cord Injury through Remote Activation of Thalamic Microglia by Cysteine Cysteine Chemokine Ligand 21. Journal of Neuroscience [Internet]. Society for Neuroscience; 2007 Aug 15;27(33):8893–902. Available from:

LaGraize SC, Labuda CJ, Rutledge MA, Jackson RL, Fuchs PN. Differential effect of anterior cingulate cortex lesion on mechanical hypersensitivity and escape/avoidance behavior in an animal model of neuropathic pain. Experimental Neurology [Internet]. Elsevier BV; 2004 Jul;188(1):139–48. Available from:

Baliki M, Al-Amin H., Atweh S, Jaber M, Hawwa N, Jabbur S., et al. Attenuation of neuropathic manifestations by local block of the activities of the ventrolateral orbito-frontal area in the rat. Neuroscience [Internet]. Elsevier BV; 2003 Sep;120(4):1093–104. Available from:

Sekiguchi M, Kobayashi H, Sekiguchi Y, Konno S, Kikuchi S. Sympathectomy Reduces Mechanical Allodynia, Tumor Necrosis Factor-Alpha Expression, and Dorsal Root Ganglion Apoptosis Following Nerve Root Crush Injury. Spine [Internet]. Ovid Technologies (Wolters Kluwer Health); 2008 May;33(11):1163–9. Available from:

Hasudungan A. [Internet]. YouTube. YouTube; 2013. Available from:

Marchand S. The Physiology of Pain Mechanisms: From the Periphery to the Brain. Rheumatic Disease Clinics of North America [Internet]. Elsevier BV; 2008 May;34(2):285–309. Available from:

Patel NB. ‘Physiology of pain’, Extracted from Kopf and Patel (Ed) “Guide to Pain Management in Low-Resource Settings”, International Association for the Study of Pain. 2010.

Paleckova V, Palecek J, McAdoo DJ, Willis WD. The non-NMDA antagonist CNQX prevents release of amino acids into the rat spinal cord dorsal horn evoked by sciatic nerve stimulation. Neuroscience Letters [Internet]. Elsevier BV; 1992 Dec;148(1-2):19–22. Available from:

Lever IJ, Bradbury EJ, Cunningham JR, Adelson DW, Jones MG, McMahon SB, et al. Brain-Derived Neurotrophic Factor Is Released in the Dorsal Horn by Distinctive Patterns of Afferent Fiber Stimulation. The Journal of Neuroscience [Internet]. Society for Neuroscience; 2001 Jun 15;21(12):4469–77. Available from:

Colvin LA, Duggan AW. Primary afferent-evoked release of immunoreactive galanin in the spinal cord of the neuropathic rat. British Journal of Anaesthesia [Internet]. Elsevier BV; 1998 Sep;81(3):436–43. Available from:

Schaible H-G, Freudenberger U, Neugebauer V, Stiller RU. Intraspinal release of immunoreactive calcitonin gene-related peptide during development of inflammation in the joint in vivo—a study with antibody microprobes in cat and rat. Neuroscience [Internet]. Elsevier BV; 1994 Oct;62(4):1293–305. Available from:

Dekin MS, Getting PA. In vitro characterization of neurons in the ventral part of the nucleus tractus solitarius. II. Ionic basis for repetitive firing patterns. Journal of Neurophysiology [Internet]. American Physiological Society; 1987 Jul;58(1):215–29. Available from:

Williams C., Wu S., Cook J, Dun N. Release of nociceptin-like substances from the rat spinal cord dorsal horn. Neuroscience Letters [Internet]. Elsevier BV; 1998 Mar;244(3):141–4. Available from:

Hutchison WD, Morton CR, Terenius L. Dynorphin A: in vivo release in the spinal cord of the cat. Brain Research [Internet]. Elsevier BV; 1990 Nov;532(1-2):299–306. Available from:

Liang F, Jones EG. Peripheral nerve stimulation increases fos immunoreactivity without affecting type II Ca2+/calmodulin-dependent protein kinase, glutamic acid decarboxylase, or GABAA receptor gene expression in cat spinal cord. Experimental Brain Research [Internet]. Springer Nature; 1996 Oct;111(3). Available from:

Bullitt E, Lee CL, Light AR, Willcockson H. The effect of stimulus duration on noxious-stimulus induced c-fos expression in the rodent spinal cord. Brain Research [Internet]. Elsevier BV; 1992 May;580(1-2):172–9. Available from:

Herdegen T, Kovary K, Leah J, Bravo R. Specific temporal and spatial distribution of JUN, FOS, and KROX-24 proteins in spinal neurons following noxious transsynaptic stimulation. The Journal of Comparative Neurology [Internet]. Wiley; 1991 Nov 1;313(1):178–91. Available from:

Wu J, Fang L, Lin Q, Willis WD. Fos expression is induced by increased nitric oxide release in rat spinal cord dorsal horn. Neuroscience [Internet]. Elsevier BV; 2000 Feb;96(2):351–7. Available from:

Palecek J, Paleckova V, Willis WD. Fos expression in spinothalamic and postsynaptic dorsal column neurons following noxious visceral and cutaneous stimuli. Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 2003 Jul;104(1):249–57. Available from:

Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. Journal of Neuroscience Methods [Internet]. Elsevier BV; 1994 Jul;53(1):55–63. Available from:

Anseloni VCZ, Ennis M, Lidow MS. Optimization of the mechanical nociceptive threshold testing with the Randall–Selitto assay. Journal of Neuroscience Methods [Internet]. Elsevier BV; 2003 Dec;131(1-2):93–7. Available from:

Christensen K, Jensen EM, Noer I. The reflex dystrophy syndrome response to treatment with systemic corticosteroids. Acta Chir Scand. 1982;148(8):653-5.

Braus DF, Krauss JK, Strobel J. The shoulder-hand syndrome after stroke: A prospective clinical trial. Annals of Neurology [Internet]. Wiley; 1994 Nov;36(5):728–33. Available from:

Gobelet C, Waldburger M, Meier JL. The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy. Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 1992 Feb;48(2):171–5. Available from:

Adami S, Fossaluzza V, Gatti D, Fracassi E, Braga V. Bisphosphonate therapy of reflex sympathetic dystrophy syndrome. Annals of the Rheumatic Diseases [Internet]. BMJ; 1997 Mar 1;56(3):201–4. Available from:

Varenna M, Zucchi F, Ghiringhelli D, Binelli L, Bevilacqua M, Bettica P, et al. Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome. A randomized, double blind, placebo controlled study. J Rheumatol. 2000 Jun;27(6):1477-83.

Manicourt D-H, Brasseur J-P, Boutsen Y, Depreseux G, Devogelaer J-P. Role of alendronate in therapy for posttraumatic complex regional pain syndrome type I of the lower extremity. Arthritis & Rheumatism [Internet]. Wiley; 2004 Nov;50(11):3690–7. Available from:

Goh EL, Chidambaram S, Ma D. Complex regional pain syndrome: a recent update. Burns & Trauma [Internet]. Springer Nature; 2017 Jan 19;5(1). Available from:

Galer BS, Miller KV, Rowbotham MC. Response to intravenous lidocaine infusion differs based on clinical diagnosis and site of nervous system injury. Neurology [Internet]. Ovid Technologies (Wolters Kluwer Health); 1993 Jun 1;43(6):1233–1233. Available from:

Glazer S, Portenoy RK. Systemic local anesthetics in pain control. Journal of Pain and Symptom Management [Internet]. Elsevier BV; 1991 Jan;6(1):30–9. Available from:

Devers A, Galer BS. Topical Lidocaine Patch Relieves a Variety of Neuropathic Pain Conditions: An Open-Label Study. The Clinical Journal of Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 2000 Sep;16(3):205–8. Available from:

Van Hilten BJ, van de Beek W-JT, Hoff JI, Voormolen JHC, Delhaas EM. Intrathecal Baclofen for the Treatment of Dystonia in Patients with Reflex Sympathetic Dystrophy. New England Journal of Medicine [Internet]. Massachusetts Medical Society; 2000 Aug 31;343(9):625–30. Available from:

Mellick GA, Mellicy LB, Mellick LB. Gabapentin in the management of reflex sympathetic dystrophy. Journal of Pain and Symptom Management [Internet]. Elsevier BV; 1995 May;10(4):265–6. Available from:

Serpell MG. Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebo-controlled trial. Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 2002 Oct;99(3):557–66. Available from:

Van de Vusse AC, Goossens VJ, Kemler MA, Weber WEJ. Screening of Patients With Complex Regional Pain Syndrome for Antecedent Infections. The Clinical Journal of Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 2001 Jun;17(2):110–4. Available from:

Rowbotham M. Gabapentin for the Treatment of Postherpetic NeuralgiaA Randomized Controlled Trial. JAMA [Internet]. American Medical Association (AMA); 1998 Dec 2;280(21):1837. Available from:

Allodynia and hyperalgesia: review
How to Cite
Dmytriiev KD, Marchuk OV, Dmytriiev KD. Allodynia and hyperalgesia: review. PMJUA [Internet]. 2018Sep.6 [cited 2019Oct.22];3(2):24-8. Available from: