Allodynia and hyperalgesia in neuropathic pain: Clinical manifestations and mechanisms

The Lancet Neurology

Volumn 13, Issue 9, 2014, Pages 924-935

  Jensen, Troels S ^a,b   Finnerup, Nanna B ^b  

^a AARHUS UNIVERSITY HOSPITAL   (Denmark)

^b AARHUS UNIVERSITY   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

BOTULINUM TOXIN A; CANNABINOID DERIVATIVE; ETIRACETAM; LAMOTRIGINE; LIDOCAINE; MEXILETINE; OPIATE DERIVATIVE; PREGABALIN; PROPOFOL; CANNABINOID RECEPTOR AFFECTING AGENT; KETAMINE; LIGAND; MORPHINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; SODIUM CHANNEL BLOCKING AGENT;

ALLODYNIA; CLINICAL ASSESSMENT; CLINICAL FEATURE; COLD ALLODYNIA; COLD HYPERALGESIA; COLD SENSATION; DRUG THERAPY; HEAT ALLODYNIA; HEAT HYPERALGESIA; HEAT SENSATION; HUMAN; HYPERALGESIA; MAGNETIC STIMULATION; NEUROPATHIC PAIN; NONHUMAN; PREVALENCE; PRIORITY JOURNAL; PUNCTATE ALLODYNIA; PUNCTATE HYPERALGESIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; STATIC EVOKED ALLODYNIA; STATIC EVOKED HYPERALGESIA; SYSTEMATIC REVIEW (TOPIC); NEURALGIA; PATHOPHYSIOLOGY; AFFERENT NERVE GROUP 1; ANALGESIC ACTIVITY; BURNING SENSATION; DIFFUSE NOXIOUS INHIBITORY CONTROL; DYSESTHESIA; EPIDEMIOLOGICAL DATA; MIDDLE CEREBRAL ARTERY OCCLUSION; MULTIPLE SCLEROSIS; NERVE COMPRESSION; NERVE FIBER C; NERVE INJURY; NEUROMODULATION; NOCICEPTIVE STIMULATION; PAIN ASSESSMENT; PAIN INTENSITY; PAIN RECEPTOR; PERIPHERAL NERVE INJURY; PERIPHERAL NEUROPATHY; PINPRICK TEST; PLACEBO EFFECT; POLYNEUROPATHY; POSTHERPETIC NEURALGIA; POSTOPERATIVE PAIN; PRESSURE SENSATION; SENSITIZATION; SKIN STIMULATION; SPINAL CORD DORSAL HORN; SPINAL CORD INJURY; TEMPORAL SUMMATION; TOUCH; TRIGEMINUS NEURALGIA;

HUMANS; HYPERALGESIA; NEURALGIA;

EID: 84906076303     PISSN: 14744422     EISSN: 14744465     Source Type: Journal    
DOI: 10.1016/S1474-4422(14)70102-4     Document Type: Review

References (154)

1. Jensen TS, Baron R, Haanpää M, et al. A new definition of neuropathic pain. Pain 2011, 152:2204-2205.
2. Jensen TS, Baron R Translation of symptoms and signs into mechanisms in neuropathic pain. Pain 2003, 102:1-8.
3. Woolf CJ Dissecting out mechanisms responsible for peripheral neuropathic pain: implications for diagnosis and therapy. Life Sci 2004, 74:2605-2610.
4. von Hehn CA, Baron R, Woolf CJ Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron 2012, 73:638-652.
5. International Association for the Study of Pain Taxonomy (accessed Jan 15, 2014). http://www.iasp-pain.org/Education/Content.aspx?ItemNumber=1698&navItemNumber=576%202011.
6. Klit H, Finnerup NB, Jensen TS Central post-stroke pain: clinical characteristics, pathophysiology, and management. Lancet Neurol 2009, 8:857-868.
7. Craig AD Pain mechanisms: labeled lines versus convergence in central processing. Annu Rev Neurosci 2003, 26:1-30.
8. Kaasa T, Romundstad L, Roald H, Skolleborg K, Stubhaug A Hyperesthesia one year after breast augmentation surgery increases the odds for persisting pain at four years: a prospective four-year follow-up study. Scand J Pain 2010, 1:75-81.
9. Truini A, Garcia-Larrea L, Cruccu G Reappraising neuropathic pain in humans-how symptoms help disclose mechanisms. Nat Rev Neurol 2013, 9:572-582.
10. Max MB Towards physiologically based treatment of patients with neuropathic pain. Pain 1990, 42:131-137.
11. van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain 2014, 155:654-662.
12. Baron R, Tölle TR, Gockel U, Brosz M, Freynhagen R A cross-sectional cohort survey in 2100 patients with painful diabetic neuropathy and postherpetic neuralgia: differences in demographic data and sensory symptoms. Pain 2009, 146:34-40.
13. Johnson RW, Wasner G, Saddier P, Baron R Herpes zoster and postherpetic neuralgia: optimizing management in the elderly patient. Drugs Aging 2008, 25:991-1006.
14. Maier C, Baron R, Tölle TR, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes. Pain 2010, 150:439-450.
15. Attal N, Fermanian C, Fermanian J, Lanteri-Minet M, Alchaar H, Bouhassira D Neuropathic pain: are there distinct subtypes depending on the aetiology or anatomical lesion?. Pain 2008, 138:343-353.
16. Loeser JD, Treede RD The Kyoto protocol of IASP Basic Pain Terminology. Pain 2008, 137:473-477.
17. Haanpää M, Attal N, Backonja M, et al. NeuPSIG guidelines on neuropathic pain assessment. Pain 2011, 152:14-27.
18. Backonja MM, Attal N, Baron R, et al. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus. Pain 2013, 154:1807-1819.
19. Finnerup NB, Sindrup SH, Jensen TS The evidence for pharmacological treatment of neuropathic pain. Pain 2010, 150:573-581.
20. Attal N, Bouhassira D, Baron R, et al. Assessing symptom profiles in neuropathic pain clinical trials: can it improve outcome?. Eur J Pain 2011, 15:441-443.
21. Woolf CJ, Mannion RJ Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999, 353:1959-1964.
22. Koltzenburg M, Scadding J Neuropathic pain. Curr Opin Neurol 2001, 14:641-647.
23. Jensen TS, Hansson PT Chapter 34 Classification of neuropathic pain syndromes based on symptoms and signs. Handb Clin Neurol 2006, 81:517-526.
24. Bennett GJ What is spontaneous pain and who has it?. J Pain 2012, 13:921-929.
25. Vase L, Nikolajsen L, Christensen B, et al. Cognitive-emotional sensitization contributes to wind-up-like pain in phantom limb pain patients. Pain 2011, 152:157-162.
26. Kugelberg E, Lindblom U The mechanism of the pain in trigeminal neuralgia. J Neurol Neurosurg Psychiatry 1959, 22:36-43.
27. Kehlet H, Jensen TS, Woolf CJ Persistent postsurgical pain: risk factors and prevention. Lancet 2006, 367:1618-1625.
28. Rowbotham MC, Fields HL The relationship of pain, allodynia and thermal sensation in post-herpetic neuralgia. Brain 1996, 119:347-354.
29. Svendsen KB, Jensen TS, Hansen HJ, Bach FW Sensory function and quality of life in patients with multiple sclerosis and pain. Pain 2005, 114:473-481.
30. Finnerup NB, Norrbrink C, Trok K, et al. Phenotypes and predictors of pain following traumatic spinal cord injury: a prospective study. J Pain 2014, 15:40-48.
31. Hatem SM, Attal N, Ducreux D, et al. Clinical, functional and structural determinants of central pain in syringomyelia. Brain 2010, 133:3409-3422.
32. Zeilig G, Enosh S, Rubin-Asher D, Lehr B, Defrin R The nature and course of sensory changes following spinal cord injury: predictive properties and implications on the mechanism of central pain. Brain 2012, 135:418-430.
33. Ochoa JL, Yarnitsky D Mechanical hyperalgesias in neuropathic pain patients: dynamic and static subtypes. Ann Neurol 1993, 33:465-472.
34. Kilo S, Schmelz M, Koltzenburg M, Handwerker HO Different patterns of hyperalgesia induced by experimental inflammation in human skin. Brain 1994, 117:385-396.
35. Koltzenburg M, Torebjörk HE, Wahren LK Nociceptor modulated central sensitization causes mechanical hyperalgesia in acute chemogenic and chronic neuropathic pain. Brain 1994, 117:579-591.
36. Gottrup H, Kristensen AD, Bach FW, Jensen TS Aftersensations in experimental and clinical hypersensitivity. Pain 2003, 103:57-64.
37. Samuelsson M, Leffler A-S, Hansson P Dynamic mechanical allodynia in the secondary hyperalgesic area in the capsaicin model-perceptually similar phenomena as in painful neuropathy?. Scand J Pain 2011, 2:85-92.
38. Warncke T, Jørum E, Stubhaug A Local treatment with the N-methyl-D-aspartate receptor antagonist ketamine, inhibit development of secondary hyperalgesia in man by a peripheral action. Neurosci Lett 1997, 227:1-4.
39. Gottrup H, Nielsen J, Arendt-Nielsen L, Jensen TS The relationship between sensory thresholds and mechanical hyperalgesia in nerve injury. Pain 1998, 75:321-329.
40. Garcia-Larrea L, Convers P, Magnin M, et al. Laser-evoked potential abnormalities in central pain patients: the influence of spontaneous and provoked pain. Brain 2002, 125:2766-2781.
41. Ducreux D, Attal N, Parker F, Bouhassira D Mechanisms of central neuropathic pain: a combined psychophysical and fMRI study in syringomyelia. Brain 2006, 129:963-976.
42. Torvin Møller A, Winther Bach F, Feldt-Rasmussen U, et al. Functional and structural nerve fiber findings in heterozygote patients with Fabry disease. Pain 2009, 145:237-245.
43. Gracely RH, Lynch SA, Bennett GJ Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain 1992, 51:175-194.
44. Campbell JN, Raja SN, Meyer RA, Mackinnon SE Myelinated afferents signal the hyperalgesia associated with nerve injury. Pain 1988, 32:89-94.
45. Landerholm AH, Hansson PT Mechanisms of dynamic mechanical allodynia and dysesthesia in patients with peripheral and central neuropathic pain. Eur J Pain 2011, 15:498-503.
46. Truini A, Biasiotta A, Di Stefano G, et al. Peripheral nociceptor sensitization mediates allodynia in patients with distal symmetric polyneuropathy. J Neurol 2013, 260:761-766.
47. Liljencrantz J, Björnsdotter M, Morrison I, et al. Altered C-tactile processing in human dynamic tactile allodynia. Pain 2013, 154:227-234.
48. Seal RP, Wang X, Guan Y, et al. Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors. Nature 2009, 462:651-655.
49. Greenspan JD, Ohara S, Sarlani E, Lenz FA Allodynia in patients with post-stroke central pain (CPSP) studied by statistical quantitative sensory testing within individuals. Pain 2004, 109:357-366.
50. Park KM, Max MB, Robinovitz E, Gracely RH, Bennett GJ Effects of intravenous ketamine, alfentanil, or placebo on pain, pinprick hyperalgesia, and allodynia produced by intradermal capsaicin in human subjects. Pain 1995, 63:163-172.
51. Gottrup H, Bach FW, Juhl G, Jensen TS Differential effect of ketamine and lidocaine on spontaneous and mechanical evoked pain in patients with nerve injury pain. Anesthesiology 2006, 104:527-536.
52. LaMotte RH, Shain CN, Simone DA, Tsai EF Neurogenic hyperalgesia: psychophysical studies of underlying mechanisms. J Neurophysiol 1991, 66:190-211.
53. Ziegler EA, Magerl W, Meyer RA, Treede RD Secondary hyperalgesia to punctate mechanical stimuli: central sensitization to A-fibre nociceptor input. Brain 1999, 122:2245-2257.
54. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 1994, 53:55-63.
55. Koltzenburg M, Lundberg LE, Torebjörk HE Dynamic and static components of mechanical hyperalgesia in human hairy skin. Pain 1992, 51:207-219.
56. Raja SN, Campbell JN, Meyer RA Evidence for different mechanisms of primary and secondary hyperalgesia following heat injury to the glabrous skin. Brain 1984, 107:1179-1188.
57. Mahn F, Hüllemann P, Gockel U, et al. Sensory symptom profiles and co-morbidities in painful radiculopathy. PLoS One 2011, 6:e18018.
58. Otto M, Bak S, Bach FW, Jensen TS, Sindrup SH Pain phenomena and possible mechanisms in patients with painful polyneuropathy. Pain 2003, 101:187-192.
59. Basbaum AI, Bautista DM, Scherrer G, Julius D Cellular and molecular mechanisms of pain. Cell 2009, 139:267-284.
60. Dib-Hajj SD, Cummins TR, Black JA, Waxman SG Sodium channels in normal and pathological pain. Annu Rev Neurosci 2010, 33:325-347.
61. Latremoliere A, Woolf CJ Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 2009, 10:895-926.
62. Devor M Sodium channels and mechanisms of neuropathic pain. J Pain 2006, 7(suppl 1):S3-12.
63. Chaplan SR, Guo HQ, Lee DH, et al. Neuronal hyperpolarization-activated pacemaker channels drive neuropathic pain. J Neurosci 2003, 23:1169-1178.
64. Biel M, Wahl-Schott C, Michalakis S, Zong X Hyperpolarization-activated cation channels: from genes to function. Physiol Rev 2009, 89:847-885.
65. Berger JV, Knaepen L, Janssen SP, et al. Cellular and molecular insights into neuropathy-induced pain hypersensitivity for mechanism-based treatment approaches. Brain Res Brain Res Rev 2011, 67:282-310.
66. Nitzan-Luques A, Minert A, Devor M, Tal M Dynamic genotype-selective "phenotypic switching" of CGRP expression contributes to differential neuropathic pain phenotype. Exp Neurol 2013, 250:194-204.
67. Coull JA, Boudreau D, Bachand K, et al. Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 2003, 424:938-942.
68. Coull JA, Beggs S, Boudreau D, et al. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005, 438:1017-1021.
69. Davis KD, Kwan CL, Crawley AP, Mikulis DJ Functional MRI study of thalamic and cortical activations evoked by cutaneous heat, cold, and tactile stimuli. J Neurophysiol 1998, 80:1533-1546.
70. Harrison JL, Davis KD Cold-evoked pain varies with skin type and cooling rate: a psychophysical study in humans. Pain 1999, 83:123-135.
71. Simone DA, Kajander KC Responses of cutaneous A-fiber nociceptors to noxious cold. J Neurophysiol 1997, 77:2049-2060.
72. Torebjörk HE, Hallin RG Perceptual changes accompanying controlled preferential blocking of A and C fibre responses in intact human skin nerves. Exp Brain Res 1973, 16:321-332.
73. Campero M, Serra J, Bostock H, Ochoa JL Slowly conducting afferents activated by innocuous low temperature in human skin. J Physiol 2001, 535:855-865.
74. Campero M, Bostock H Unmyelinated afferents in human skin and their responsiveness to low temperature. Neurosci Lett 2010, 470:188-192.
75. Madrid R, de la Peña E, Donovan-Rodriguez T, Belmonte C, Viana F Variable threshold of trigeminal cold-thermosensitive neurons is determined by a balance between TRPM8 and Kv1 potassium channels. J Neurosci 2009, 29:3120-3131.
76. Namer B, Kleggetveit IP, Handwerker H, Schmelz M, Jorum E Role of TRPM8 and TRPA1 for cold allodynia in patients with cold injury. Pain 2008, 139:63-72.
77. Zimmermann K, Deuis JR, Inserra MC, et al. Analgesic treatment of ciguatoxin-induced cold allodynia. Pain 2013, 154:1999-2006.
78. Serra J, Solà R, Quiles C, et al. C-nociceptors sensitized to cold in a patient with small-fiber neuropathy and cold allodynia. Pain 2009, 147:46-53.
79. Jørum E, Warncke T, Stubhaug A Cold allodynia and hyperalgesia in neuropathic pain: the effect of N-methyl-D-aspartate (NMDA) receptor antagonist ketamine-a double-blind, cross-over comparison with alfentanil and placebo. Pain 2003, 101:229-235.
80. Thunberg T Förnimmelserne vid till samma ställe lokaliserad, samtidigt pägäende köld-och värmeretning. Uppsala Läkfören Förh 1896, 1:489-495.
81. Craig AD, Bushnell MC The thermal grill illusion: unmasking the burn of cold pain. Science 1994, 265:252-255.
82. Craig AD, Reiman EM, Evans A, Bushnell MC Functional imaging of an illusion of pain. Nature 1996, 384:258-260.
83. Kern D, Pelle-Lancien E, Luce V, Bouhassira D Pharmacological dissection of the paradoxical pain induced by a thermal grill. Pain 2008, 135:291-299.
84. Tominaga M, Caterina MJ Thermosensation and pain. J Neurobiol 2004, 61:3-12.
85. Clapham DE TRP channels as cellular sensors. Nature 2003, 426:517-524.
86. Patapoutian A, Peier AM, Story GM, Viswanath V ThermoTRP channels and beyond: mechanisms of temperature sensation. Nat Rev Neurosci 2003, 4:529-539.
87. Belmonte C, Brock JA, Viana F Converting cold into pain. Exp Brain Res 2009, 196:13-30.
88. Madrid R, Donovan-Rodríguez T, Meseguer V, Acosta MC, Belmonte C, Viana F Contribution of TRPM8 channels to cold transduction in primary sensory neurons and peripheral nerve terminals. J Neurosci 2006, 26:12512-12525.
89. McKemy DD The molecular and cellular basis of cold sensation. ACS Chem Neurosci 2013, 4:238-247.
90. Gauchan P, Andoh T, Kato A, Kuraishi Y Involvement of increased expression of transient receptor potential melastatin 8 in oxaliplatin-induced cold allodynia in mice. Neurosci Lett 2009, 458:93-95.
91. Kono T, Satomi M, Suno M, et al. Oxaliplatin-induced neurotoxicity involves TRPM8 in the mechanism of acute hypersensitivity to cold sensation. Brain Behav 2012, 2:68-73.
92. Wasner G, Naleschinski D, Binder A, Schattschneider J, McLachlan EM, Baron R The effect of menthol on cold allodynia in patients with neuropathic pain. Pain Med 2008, 9:354-358.
93. Park SB, Lin CS, Krishnan AV, Goldstein D, Friedlander ML, Kiernan MC Dose effects of oxaliplatin on persistent and transient Na+ conductances and the development of neurotoxicity. PLoS One 2011, 6:e18469.
94. Minett MS, Falk S, Santana-Varela S, et al. Pain without nociceptors? Nav1.7-independent pain mechanisms. Cell Reports 2014, 6:301-312.
95. Sittl R, Lampert A, Huth T, et al. Anticancer drug oxaliplatin induces acute cooling-aggravated neuropathy via sodium channel subtype Na(V)1.6-resurgent and persistent current. Proc Natl Acad Sci USA 2012, 109:6704-6709.
96. Zhao M, Isami K, Nakamura S, Shirakawa H, Nakagawa T, Kaneko S Acute cold hypersensitivity characteristically induced by oxaliplatin is caused by the enhanced responsiveness of TRPA1 in mice. Mol Pain 2012, 8:55.
97. Nassini R, Gees M, Harrison S, et al. Oxaliplatin elicits mechanical and cold allodynia in rodents via TRPA1 receptor stimulation. Pain 2011, 152:1621-1631.
98. Descoeur J, Pereira V, Pizzoccaro A, et al. Oxaliplatin-induced cold hypersensitivity is due to remodelling of ion channel expression in nociceptors. EMBO Mol Med 2011, 3:266-278.
99. Shirahama M, Ushio S, Egashira N, et al. Inhibition of Ca2+/calmodulin-dependent protein kinase II reverses oxaliplatin-induced mechanical allodynia in rats. Mol Pain 2012, 8:26.
100. Vestergaard K, Nielsen J, Andersen G, Ingeman-Nielsen M, Arendt-Nielsen L, Jensen TS Sensory abnormalities in consecutive, unselected patients with central post-stroke pain. Pain 1995, 61:177-186.
101. Fruhstorfer H Thermal sensibility changes during ischemic nerve block. Pain 1984, 20:355-361.
102. Yarnitsky D, Ochoa JL Release of cold-induced burning pain by block of cold-specific afferent input. Brain 1990, 113:893-902.
103. Ochoa JL, Yarnitsky D The triple cold syndrome. Cold hyperalgesia, cold hypoaesthesia and cold skin in peripheral nerve disease. Brain 1994, 117:185-197.
104. Campero M, Baumann TK, Bostock H, Ochoa JL Human cutaneous C fibres activated by cooling, heating and menthol. J Physiol 2009, 587:5633-5652.
105. Craig AD, Chen K, Bandy D, Reiman EM Thermosensory activation of insular cortex. Nat Neurosci 2000, 3:184-190.
106. McCoy ES, Taylor-Blake B, Street SE, Pribisko AL, Zheng J, Zylka MJ Peptidergic CGRPα primary sensory neurons encode heat and itch and tonically suppress sensitivity to cold. Neuron 2013, 78:138-151.
107. Callsen MG, Moller AT, Sorensen K, Jensen TS, Finnerup NB Cold hyposensitivity after topical application of capsaicin in humans. Exp Brain Res 2008, 191:447-452.
108. Johanek LM, Meyer RA, Friedman RM, et al. A role for polymodal C-fiber afferents in nonhistaminergic itch. J Neurosci 2008, 28:7659-7669.
109. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997, 389:816-824.
110. Brederson JD, Kym PR, Szallasi A Targeting TRP channels for pain relief. Eur J Pharmacol 2013, 716:61-76.
111. Treede RD, Meyer RA, Raja SN, Campbell JN Peripheral and central mechanisms of cutaneous hyperalgesia. Prog Neurobiol 1992, 38:397-421.
112. Wu Q, García-Larrea L, Mertens P, Beschet A, Sindou M, Mauguière F Hyperalgesia with reduced laser evoked potentials in neuropathic pain. Pain 1999, 80:209-214.
113. Madsen CS, Johnsen B, Fuglsang-Frederiksen A, Jensen TS, Finnerup NB The effect of nerve compression and capsaicin on contact heat-evoked potentials related to Aδ- and C-fibers. Neuroscience 2012, 223:92-101.
114. Dib-Hajj SD, Black JA, Waxman SG Voltage-gated sodium channels: therapeutic targets for pain. Pain Med 2009, 10:1260-1269.
115. Dib-Hajj SD, Rush AM, Cummins TR, et al. Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain 2005, 128:1847-1854.
116. Ørstavik K, Weidner C, Schmidt R, et al. Pathological C-fibres in patients with a chronic painful condition. Brain 2003, 126:567-578.
117. Ma W, Zhang Y, Bantel C, Eisenach JC Medium and large injured dorsal root ganglion cells increase TRPV-1, accompanied by increased alpha2C-adrenoceptor co-expression and functional inhibition by clonidine. Pain 2005, 113:386-394.
118. Kim HY, Park CK, Cho IH, Jung SJ, Kim JS, Oh SB Differential changes in TRPV1 expression after trigeminal sensory nerve injury. J Pain 2008, 9:280-288.
119. Urano H, Ara T, Fujinami Y, Hiraoka BY Aberrant TRPV1 expression in heat hyperalgesia associated with trigeminal neuropathic pain. Int J Med Sci 2012, 9:690-697.
120. Dray A Neuropathic pain: emerging treatments. Br J Anaesth 2008, 101:48-58.
121. Colombo E, Francisconi S, Faravelli L, Izzo E, Pevarello P Ion channel blockers for the treatment of neuropathic pain. Future Med Chem 2010, 2:803-842.
122. Kishore-Kumar R, Max MB, Schafer SC, et al. Desipramine relieves postherpetic neuralgia. Clin Pharmacol Ther 1990, 47:305-312.
123. Vranken JH, Hollmann MW, van der Vegt MH, et al. Duloxetine in patients with central neuropathic pain caused by spinal cord injury or stroke: a randomized, double-blind, placebo-controlled trial. Pain 2011, 152:267-273.
124. Yucel A, Ozyalcin S, Koknel Talu G, et al. The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study. Eur J Pain 2005, 9:407-416.
125. Kim JS, Bashford G, Murphy TK, Martin A, Dror V, Cheung R Safety and efficacy of pregabalin in patients with central post-stroke pain. Pain 2011, 152:1018-1023.
126. Stacey BR, Barrett JA, Whalen E, Phillips KF, Rowbotham MC Pregabalin for postherpetic neuralgia: placebo-controlled trial of fixed and flexible dosing regimens on allodynia and time to onset of pain relief. J Pain 2008, 9:1006-1017.
127. Serpell MG Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebo-controlled trial. Pain 2002, 99:557-566. the Neuropathic pain study group.
128. Sindrup SH, Andersen G, Madsen C, Smith T, Brøsen K, Jensen TS Tramadol relieves pain and allodynia in polyneuropathy: a randomised, double-blind, controlled trial. Pain 1999, 83:85-90.
129. Watson CP, Babul N Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. Neurology 1998, 50:1837-1841.
130. Teixeira MJ, Okada M, Moscoso AS, et al. Methadone in post-herpetic neuralgia: a pilot proof-of-concept study. Clinics (Sao Paulo) 2013, 68:1057-1060.
131. Nurmikko TJ, Serpell MG, Hoggart B, Toomey PJ, Morlion BJ, Haines D Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain 2007, 133:210-220.
132. Vestergaard K, Andersen G, Gottrup H, Kristensen BT, Jensen TS Lamotrigine for central poststroke pain: a randomized controlled trial. Neurology 2001, 56:184-190.
133. Wallace MS, Magnuson S, Ridgeway B Efficacy of oral mexiletine for neuropathic pain with allodynia: a double-blind, placebo-controlled, crossover study. Reg Anesth Pain Med 2000, 25:459-467.
134. Rowbotham MC, Davies PS, Fields HL Topical lidocaine gel relieves postherpetic neuralgia. Ann Neurol 1995, 37:246-253.
135. Ranoux D, Attal N, Morain F, Bouhassira D Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol 2008, 64:274-283.
136. Leung A, Wallace MS, Ridgeway B, Yaksh T Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain. Pain 2001, 91:177-187.
137. Baranowski AP, De Courcey J, Bonello E A trial of intravenous lidocaine on the pain and allodynia of postherpetic neuralgia. J Pain Symptom Manage 1999, 17:429-433.
138. Attal N, Gaudé V, Brasseur L, et al. Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study. Neurology 2000, 54:564-574.
139. Finnerup NB, Biering-Sørensen F, Johannesen IL, et al. Intravenous lidocaine relieves spinal cord injury pain: a randomized controlled trial. Anesthesiology 2005, 102:1023-1030.
140. Attal N, Guirimand F, Brasseur L, Gaude V, Chauvin M, Bouhassira D Effects of IV morphine in central pain: a randomized placebo-controlled study. Neurology 2002, 58:554-563.
141. Attal N, Rouaud J, Brasseur L, Chauvin M, Bouhassira D Systemic lidocaine in pain due to peripheral nerve injury and predictors of response. Neurology 2004, 62:218-225.
142. Eide PK, Jørum E, Stubhaug A, Bremnes J, Breivik H Relief of post-herpetic neuralgia with the N-methyl-D-aspartic acid receptor antagonist ketamine: a double-blind, cross-over comparison with morphine and placebo. Pain 1994, 58:347-354.
143. Gormsen L, Finnerup NB, Almqvist PM, Jensen TS The efficacy of the AMPA receptor antagonist NS1209 and lidocaine in nerve injury pain: a randomized, double-blind, placebo-controlled, three-way crossover study. Anesth Analg 2009, 108:1311-1319.
144. Max MB, Byas-Smith MG, Gracely RH, Bennett GJ Intravenous infusion of the NMDA antagonist, ketamine, in chronic posttraumatic pain with allodynia: a double-blind comparison to alfentanil and placebo. Clin Neuropharmacol 1995, 18:360-368.
145. Canavero S, Bonicalzi V Intravenous subhypnotic propofol in central pain: a double-blind, placebo-controlled, crossover study. Clin Neuropharmacol 2004, 27:182-186.
146. Simpson DM, Schifitto G, Clifford DB, et al. Pregabalin for painful HIV neuropathy: a randomized, double-blind, placebo-controlled trial. Neurology 2010, 74:413-420. the 1066 HIV Neuropathy Study Group.
147. Finnerup NB, Sindrup SH, Bach FW, Johannesen IL, Jensen TS Lamotrigine in spinal cord injury pain: a randomized controlled trial. Pain 2002, 96:375-383.
148. Falah M, Madsen C, Holbech JV, Sindrup SH A randomized, placebo-controlled trial of levetiracetam in central pain in multiple sclerosis. Eur J Pain 2012, 16:860-869.
149. Haroutiunian S, Nikolajsen L, Bendtsen TF, et al. Primary afferent input critical for maintaining spontaneous pain in peripheral neuropathy. Pain 2014, published online April 2. http://dx.doi.org/10.1016/j.pain.2014.03.022.
150. Moreno-Duarte I, Morse LR, Alam M, Bikson M, Zafonte R, Fregni F Targeted therapies using electrical and magnetic neural stimulation for the treatment of chronic pain in spinal cord injury. Neuroimage 2014, 85:1003-1013.
151. Nardone R, Höller Y, Leis S, et al. Invasive and non-invasive brain stimulation for treatment of neuropathic pain in patients with spinal cord injury: a review. J Spinal Cord Med 2014, 37:19-31.
152. Witting N, Svensson P, Jensen TS Differential recruitment of endogenous pain inhibitory systems in neuropathic pain patients. Pain 2003, 103:75-81.
153. Petersen GL, Finnerup NB, Nørskov KN, et al. Placebo manipulations reduce hyperalgesia in neuropathic pain. Pain 2012, 153:1292-1300.
154. Gilron I, Jensen TS, Dickenson AH Combination pharmacotherapy for management of chronic pain: from bench to bedside. Lancet Neurol 2013, 12:1084-1095.