The corneal pain system. Part I: The missing piece of the dry eye puzzle

Ocular Surface

Volumn 10, Issue 1, 2012, Pages 2-14

  Rosenthal, Perry ^a   Borsook, David ^b  

^a Boston Foundation for Sight   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Allodynia; Corneal pain; Dry eye; Hyperalgesia; Inflammation; Nociceptive network; Pain

Indexed keywords

ARTICLE; CLINICAL FEATURE; CORNEA EPITHELIUM; CORNEA PAIN; DRY EYE; HUMAN; HYPERALGESIA; KERATITIS; NERVOUS SYSTEM INFLAMMATION; NEUROPATHIC PAIN; NONHUMAN; OSMOTIC STRESS; PAIN; PATHOGENESIS; SENSITIZATION; SIGNAL TRANSDUCTION; TEAR FLOW; CORNEA; CORNEA DISEASE; EYE PAIN; INNERVATION; NOCICEPTIVE RECEPTOR; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW; TRIGEMINAL NERVE;

CORNEA; CORNEAL DISEASES; DRY EYE SYNDROMES; EYE PAIN; HUMANS; HYPERALGESIA; NOCICEPTORS; TRIGEMINAL NERVE;

EID: 84861318558     PISSN: 15420124     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jtos.2012.01.002     Document Type: Review

References (127)

1. Brewitt H, Sistani F. Dry eye disease: the scale of the problem. Surv Ophthalmol 2001;45(Suppl 2):S199-202
2. Pflugfelder SC. Prevalence, burden, and pharmacoeconomics of dry eye disease. Am J Manag Care 2008;14(3 Suppl):S102-6 (Pubitemid 351656967)
3. Reddy P, Grad O, Rajagopalan K. The economic burden of dry eye: a conceptual framework and preliminary assessment. Cornea 2004;23:751-61 (Pubitemid 39447303)
4. Schein OL, Tielsch JM, Munos B, et al. Relation between signs and symptoms of dry eye in the elderly: a population-based perspective. Ophthalmology 1997;104:1395-401 (Pubitemid 28116804)
5. Bjerrum KB. Test and symptoms in keratoconjunctivitis sicca and their correlation. Acta Ophthalmol Scand 1996;74:436-41 (Pubitemid 26390485)
6. Begley CG, Chalmers RL, Abetz L, et al. The relationship between habitual patient-reported symptoms and clinical signs among patients with dry eye of varying severity. Invest Ophthalmol Vis Sci 2003;44:4753-61 (Pubitemid 37315288)
7. Belmonte C. Eye dryness sensations after refractive surgery: impaired tear secretion or "phantom" cornea? J Refract Surg 2007;23:598-602
8. Rosenthal P, Baran I, Jacobs DS. Corneal pain without stain. Is it real? Ocul Surf 2009;7:28-40
9. Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 2005;9:463-84 (Pubitemid 40836040)
10. Wagner KJ, Sprenger T, Kochs EF, et al. Imaging human cerebral pain modulation by dose-dependent opioid analgesia: a positron emission tomography activation study using remifentanil. Anesthesiology 2007;106:548-56 (Pubitemid 46662221)
11. Baliki MN, Geha PY, Apkarian AV. Spontaneous pain and brain activity in neuropathic pain: functional MRI and pharmacologic functional MRI studies. Curr Pain Headache Rep 2007;11:171-7 (Pubitemid 46851246)
12. Geha PY, Baliki MN, Chialvo DR, et al. Brain activity for spontaneous pain of postherpetic neuralgia and its modulation by lidocaine patch therapy. Pain 2007;128(1-2):88-100 (Pubitemid 46216604)
13. Fu Y, Han J, Ishola T, et al. PKA and ERK, but not PKC, in the amygdala contribute to pain-related synaptic plasticity and behavior. Mol Pain 2008;4:26
14. Upadhyay J, Knudsen J, Anderson J, et al. Noninvasive mapping of human trigeminal brainstem pathways. Magn Reson Med 2008;60: 1037-46
15. Villemure C, Bushnell MC. Cognitive modulation of pain: how do attention and emotion influence pain processing? Pain 2002;95: 195-9 (Pubitemid 34142642)
16. Lacroix-Fralish ML, Mogil JS. Progress in genetic studies of pain and analgesia. Annu Rev Pharmacol Toxicol 2009;49:97-121
17. Mueller LJ, Vresesn GF, Pels L, et al. Architecture of human corneal nerves. Invest Ophthalmol Vis Sci 1997;38:985-94 (Pubitemid 27193524)
18. Muller LJ, Marfurt CF, Kruse F, Tervo TM. Corneal nerves: structure, contents and function. Exp Eye Res 2003;76:521-42 (Pubitemid 36411929)
19. Guthoff RF, Wienss H, Hahnel C, Wree A. Epithelial innervation of human cornea. Cornea 2005;24:608-13
20. Brock JA, Pianova S, Belmonte C. Differences between nerve terminal impulses of polymodal nociceptors and cold sensory receptors of the guinea-pig cornea. J Physiol 2001;533(Pt 2):493-501 (Pubitemid 32520003)
21. Belmonte C, Carmen Acosta M, Gallar J. Neural basis of sensation in intact and injured corneas. Exp Eye Res 2004;78:513-25 (Pubitemid 38183329)
22. Patapoutian A, Tate S, Woolf CJ. Transient receptor potential channels: targeting pain at the source. Nat Rev Drug Discov 2009;8:55-68
23. Mergler S, Garreis F, Sahlmuller M, et al. Thermosensitive transient receptor potential channels (thermo-TRPs) in human corneal epithelial cells. J Cell Physiol 2010 Nov 10 [Epub ahead of print]
24. Parra A, Madrid R, Echevarria D, et al. Ocular surface wetness is regulated by TRPM8-dependent cold thermoreceptors of the cornea. Nat Med 2010;16:1396-9
25. Hirata H, Meng ID. Cold-sensitive corneal afferents respond to a variety of ocular stimuli central to tear production: implications for dry eye disease. Invest Ophthalmol Vis Sci 2010;51:3969-76
26. Hirata H, Okamoto K, Tashiro A, Bereiter DA. A novel class of neurons at the trigeminal subnucleus interpolaris/caudalis transition region monitors ocular surface fluid status and modulates tear production. J Neurosci 2004;24:4224-32 (Pubitemid 38620798)
27. Pan Z, Wang Z, Yang H, et al. TRPV1 activation is required for hyper-tonicity stimulated inflammatory cytokine release in human corneal epithelial cells. Invest Ophthalmol Vis Sci 2011;52:485-93
28. Ji RR, Samad TA, Jin SX, et al. p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 2002;36:57-68
29. Belmonte C, Giraldez F. Responses of cat corneal sensory receptors to mechanical and thermal stimulation. J Physiol 1981;321:355-68 (Pubitemid 12248101)
30. Niederkorn JY, Stern ME, Pflugfelder SC, et al. Desiccating stress induces T cell-mediated Sjogren's Syndrome-like lacrimal keratocon-junctivitis. J Immunol 2006;176:3950-7 (Pubitemid 44264372)
31. Luo L, Li DQ, Corrales RM, Pflugfelder SC. Hyperosmolar saline is a proinflammatory stress on the mouse ocular surface. Eye Contact Lens 2005;31:186-93 (Pubitemid 43197004)
32. Pflugfelder SC, de Paiva CS, Li DQ, Stern ME. Epithelial-immune cell interaction in dry eye. Cornea 2008;27(Suppl 1):S9-11
33. Fernandez KB, Maguire MG, Peskin E, et al. Correlation of patients' and clinicians' global assessment scores of dry eye disease severity and tear osmolarity in patients with mild to moderate dry eye disease. Invest Ophthalmol Vis Sci 2011;52(6). ARVO Poster 3791/ D924
34. Vasan RA, Berenberg TL, Starr CE. Correlation of tear osmolarity and Ocular Surface Disease Index scores in healthy volunteers. Invest Ophthalmol Vis Sci 2011;52(6). ARVO Poster 3794/D927
35. Woolf CJ, Safieh-Garabedian B, Ma QP, et al. Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity. Neuroscience 1994;62:327-31
36. Lewin GR, Rueff A, Mendell LM. Peripheral and central mechanisms of NGF-induced hyperalgesia. Eur J Neurosci 1994;6:1903-12
37. Black PH. Stress and the inflammatory response: a review of neurogenic inflammation. Brain Behav Immun 2002;16:622-53 (Pubitemid 36027055)
38. Enriquez-de-Salamanca A, Castellanos E, Stern ME, et al. Tear cytokine and chemokine analysis and clinical correlations in evaporative-type dry eye disease. Mol Vis 2010;16:862-73
39. Reichling DB, Levine JD. Critical role of nociceptor plasticity in chronic pain. Trends Neurosci 2009;32:611-8
40. Hoffmann T, Sauer SK, Horch RE, Reeh PW. Sensory transduction in peripheral nerve axons elicits ectopic action potentials. J Neurosci 2008;28:6281-4
41. Xiao HS, Huang QH, Zhang FX, et al. Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proc Natl Acad Sci U S A 2002;99:8360-5
42. Neumann S, Doubell TP, Leslie T, Woolf CJ. Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons. Nature 1996;384(6607):360-4 (Pubitemid 26408518)
43. Amir R, Devor M. Axonal cross-excitation in nerve-end neuromas: comparison of A-and C-fibers. J Neurophysiol 1992;68:1160-6
44. Devor M. Sodium channels and mechanisms of neuropathic pain. J Pain 2006;7(1 Suppl 1):S3-12
45. Herrero JF, Laird JM, Lopez-Garcia JA. Wind-up of spinal cord neurones and pain sensation: much ado about something? Prog Neurobiol 2000;61:169-203 (Pubitemid 30110477)
46. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science 2000;288(5472):1765-9
47. Bhave G, Gereau 4th RW. Posttranslational mechanisms of peripheral sensitization. J Neurobiol 2004;61:88-106 (Pubitemid 39287772)
48. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 2009;10:895-926
49. Ren K, Dubner R. Descending modulation in persistent pain: an update. Pain 2002;100(1-2):1-6 (Pubitemid 35305118)
50. Sanada T, Kohase H, Makino K, Umino M. Effects of alpha-adrenergic agonists on pain modulation in diffuse noxious inhibitory control. J Med Dent Sci 2009;56:17-24
51. Sprenger C, Bingel U, Buchel C. Treating pain with pain: supraspinal mechanisms of endogenous analgesia elicited by heterotopic noxious conditioning stimulation. Pain 2011;152:428-39
52. Davis GW. Homeostatic control of neural activity: from phenomenology to molecular design. Annu Rev Neurosci 2006;29:307-23 (Pubitemid 44476848)
53. Honore P, Rogers SD, Schwei MJ, et al. Murine models of inflammatory, neuropathic and cancer pain each generates a unique set of neurochemical changes in the spinal cord and sensory neurons. Neuroscience 2000;98:585-98 (Pubitemid 30408178)
54. Treede RD, Jensen TS, Campbell JN, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008;70:1630-5 (Pubitemid 351620320)
55. Cruccu G, Sommer C, Anand P, et al. EFNS guidelines on neuropathic pain assessment: revised 2009. Eur J Neurol 2010;17:1010-8
56. Navarro X, Vivo M, Valero-Cabre A. Neural plasticity after peripheral nerve injury and regeneration. Prog Neurobiol 2007;82:163-201 (Pubitemid 47088051)
57. Walton KD, Dubois M, Llinas RR. Abnormal thalamocortical activity in patients with Complex Regional Pain Syndrome (CRPS) type I. Pain 2010;150:41-51
58. Borsook D, Upadhyay J, Chudler EH, Becerra L. A key role of the basal ganglia in pain and analgesiaeinsights gained through human functional imaging. Mol Pain 2010;6:27
59. Jensen KB, Kosek E, Petzke F, et al. Evidence of dysfunctional pain inhibition in fibromyalgia reflected in rACC during provoked pain. Pain 2009;144(1-2):95-100
60. Svendsen F, Tjolsen A, Gjerstad J, Hole K. Long term potentiation of single WDR neurons in spinalized rats. Brain Res 1999;816:487-92 (Pubitemid 29225398)
61. Tan AM, Stamboulian S, Chang YW, et al. Neuropathic pain memory is maintained by Rac1-regulated dendritic spine remodeling after spinal cord injury. J Neurosci 2008;28:13173-83
62. Becerra L, Morris S, Bazes S, et al. Trigeminal neuropathic pain alters responses in CNS circuits to mechanical (brush) and thermal (cold and heat) stimuli. J Neurosci 2006;26:10646-57
63. Yoon KC, Ahn KY, Choi W, et al. Tear production and ocular surface changes in experimental dry eye after elimination of desiccating stress. Invest Ophthalmol Vis Sci 2011;52:7267-73
64. McCulley JP, Shine W. A compositional based model for the tear film lipid layer. Trans Am Ophthalmol Soc 1997;95:79-88. discussion 88-93
65. Tsubota K. Tear dynamics and dry eye. Prog Retin Eye Res 1998;17: 565-96 (Pubitemid 28432981)
66. Foulks GN. The correlation between the tear film lipid layer and dry eye disease. Surv Ophthalmol 2007;52:369-74 (Pubitemid 46898549)
67. Lemp MA, Nichols KK. Blepharitis in the United States 2009: a survey-based perspective on prevalence and treatment. Ocul Surf 2009;7(2 Suppl):S1-14
68. Arita R, Itoh K, Maeda S, et al. Efficacy of diagnostic criteria for the differential diagnosis between obstructive meibomian gland dysfunction and aqueous deficiency dry eye. Jpn J Ophthalmol 2010;54:387-91
69. Kawasaki A, Borruat FX. Photophobia associated with a demyelinating lesion of the retrochiasmal visual pathway. Am J Ophthalmol 2006;142: 854-6 (Pubitemid 44584129)
70. Noseda R, Kainz V, Jakubowski M, et al. A neural mechanism for exacerbation of headache by light. Nat Neurosci 2010;13:239-45
71. Kowacs PA, Piovesan EJ, Werneck LC, et al. Critical flicker frequency in migraine: a controlled study in patients without prophylactic therapy. Cephalalgia 2005;25:339-43 (Pubitemid 40559415)
72. Okamoto K, Tashiro A, Chang Z, Bereiter DA. Bright light activates a trigeminal nociceptive pathway. Pain 2010;149:235-42
73. Maleki N, Becerra L, Upadhyay J, et al. Direct optic nerve pulvinar connections defined by diffusion MR tractography in humans: Implications for photophobia. Hum Brain Mapp 2011 Feb 17. doi:10.1002/hbm.21194 [Epub ahead of print]
74. Serra J, Campero M, Bostock H, Ochoa J. Two types of C nociceptors in human skin and their behavior in areas of capsaicin-induced secondary hyperalgesia. J Neurophysiol 2004;91:2770-81 (Pubitemid 38649782)
75. Treede RD, Meyer RA, Raja SN, Campbell JN. Peripheral and central mechanisms of cutaneous hyperalgesia. Prog Neurobiol 1992;38: 397-421
76. Koppert W, Ostermeier N, Sittl R, et al. Low-dose lidocaine reduces secondary hyperalgesia by a central mode of action. Pain 2000;85(1-2): 217-24 (Pubitemid 30110762)
77. Liverman CS, Brown JW, Sandhir R, et al. Oestrogen increases nociception through ERK activation in the trigeminal ganglion: evidence for a peripheral mechanism of allodynia. Cephalalgia 2009;29:520-31
78. Rosenthal P, Bradley J. Co morbid pain in the innervation territories of the non-ophthalmic branches of the trigeminal nerve triggered by corneal neuropathic pain can be mitigated by modulators of corneal nociceptor Na+ channel function. Invest Ophthalmol Vis Sci 2010;51(5). ARVO Poster 3404/D990
79. Jones EG. Thalamocortical dysrhythmia and chronic pain. Pain 2010;150:4-5
80. Borsook D, Rosenthal P. Chronic (neuropathic) corneal pain and blepharospasm: five case reports. Pain 2011;152:2417-31
81. Niederer RL, Perumal D, Sherwin T, McGhee CN. Age-related differences in the normal human cornea: a laser scanning in vivo confocal microscopy study. Br J Ophthalmol 2007;91:1165-9 (Pubitemid 47344890)
82. Benitez del Castillo JM, Acosta MC, Wassfi MA, et al. Relation between corneal innervation with confocal microscopy and corneal sensitivity with noncontact esthesiometry in patients with dry eye. Invest Ophthalmol Vis Sci 2007;48:173-81 (Pubitemid 47251400)
83. Acosta MC, Belmonte C, Gallar J. Sensory experiences in humans and single-unit activity in cats evoked by polymodal stimulation of the cornea. J Physiol 2001;534(Pt 2):511-25 (Pubitemid 32677745)
84. Taguchi T, Ota H, Matsuda T, et al. Cutaneous C-fiber nociceptor responses and nociceptive behaviors in aged Sprague-Dawley rats. Pain 2010;151:771-82
85. Zhang X, Chen Q, Chen W, et al. Tear dynamics and corneal confocal microscopy of subjects with mild self-reported office dry eye. Ophthalmology 2011;118:902-7
86. Rogers ML, Duffy JP. Surgical aspects of chronic post-thoracotomy pain. Eur J Cardiothorac Surg 2000;18:711-6
87. Richdale K, Sinnott LT, Skadahl E, Nichols JJ. Frequency of and factors associated with contact lens dissatisfaction and discontinuation. Cornea 2007;26:168-74 (Pubitemid 46168286)
88. Xu B, Chen X. The role of mechanical stress on the formation of a curly pattern of human hair. J Mech Behav Biomed Mater 2011;4:212-21
89. Ferrari LF, Bogen O, Levine JD. Nociceptor subpopulations involved in hyperalgesic priming. Neuroscience 2010;165:896-901
90. Thakur A, Willcox MD. Contact lens wear alters the production of certain inflammatory mediators in tears. Exp Eye Res 2000;70: 255-9 (Pubitemid 30658896)
91. Kallinikos P, Efron N. On the etiology of keratocyte loss during contact lens wear. Invest Ophthalmol Vis Sci 2004;45:3011-20 (Pubitemid 39121830)
92. Dieleman JP, Kerklaan J, Huygen FJPM, et al. Incidence rates and treatment of neuropathic pain conditions in the general population. Pain 2008;137:681-8
93. Rosenthal P, Bradley J. Dry eye-like symptoms without dry eyes is a neurological disease. Invest Ophthalmol Vis Sci 2011;52(6). ARVO Poster 3855/D988
94. Invernizzi P. Future directions in genetic for autoimmune diseases. J Autoimmun 2009;33:1-2
95. Tsubota K, Toda I, Yagi Y, et al. Three different types of dry eye syndrome. Cornea 1994;13:202-9 (Pubitemid 24129152)
96. Sendecka M, Baryluk A, Polz-Dacewicz M. Prevalence and risk factors of dry eye syndrome. Przegl Epidemiol 2004;58:227-33. Polish
97. Alboni S, Cervia D, Sugama S, Conti B. Interleukin 18 in the CNS. J Neuroinflammation 2010;7:9
98. Miyoshi K, Obata K, Kondo T, et al. Interleukin-18-mediated microglia/astrocyte interaction in the spinal cord enhances neuropathic pain processing after nerve injury. J Neurosci 2008;28(48):12775-87
99. Fillingim RB, King CD, Ribeiro-Dasilva MC, et al. Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain 2009;10:447-85
100. Hovanesian JA, Shah SS, Maloney RK. Symptoms of dry eye and recurrent erosion syndrome after refractive surgery. J Cataract Refract Surg 2001;27:577-84
101. Hamawy AH, Farkas JP, Fagien S, Rohrich RJ. Preventing and managing dry eyes after periorbital surgery: a retrospective review. Plast Reconstr Surg 2009;123:353-9
102. Kimball BY, Sorenson JM, Cunningham D. Repeat Gamma Knife surgery for trigeminal neuralgia: long-term results. J Neurosurg 2010;113(Suppl):178-83
103. Cumurcu T, Sezer E, Kilic R, Bulut Y. Comparison of dose-related ocular side effects during systemic isotretinoin administration. Eur J Ophthalmol 2009;19:196-200
104. de Vries S, Geerards AJ. Long-term sequelae of isolated chemical "airbag" keratitis. Cornea 2007;26:998-9 (Pubitemid 47329809)
105. Backman HA. The effects of PUVA on the eye. Am J Optom Physiol Opt 1982;59:86-9 (Pubitemid 12092335)
106. Parsons JT, Bova FJ, Mendenhall WM, et al. Response of the normal eye to high dose radiotherapy. Oncology 1996;10:837-47. discussion 847-8, 851-2 (Pubitemid 126520853)
107. Mrugacz M, Lebensztejn D. Ocular findings in hepatitis C patients treated with interferon. Klin Oczna 2010;112(7-9):253-6. Polish
108. Baudouin C, Labbe A, Liang H, et al. Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res 2010;29:312-34
109. Schaumberg DA, Dana R, Buring JE, Sullivan DA. Prevalence of dry eye disease among US men: estimates from the Physicians' Health Studies. Arch Ophthalmol 2009;127:763-8
110. Akinci A, Cetinkaya E, Aycan Z. Dry eye syndrome in diabetic children. Eur J Ophthalmol 2007;17:873-8 (Pubitemid 351262895)
111. Arevalo JF, Lowder CY, Muci-Mendoza R. Ocular manifestations of systemic lupus erythematosus. Curr Opin Ophthalmol 2002;13:404-10 (Pubitemid 35397651)
112. Feist E, Pleyer U. Diseases of the outer eye in rheumatoid arthritis. Z Rheumatol 2010;69:403-10
113. Graus F, Paou A, Anderson NE. Sensory neuropathy and Sjogren's syndrome: clinical and immunologic study of two patients. Neurology 1988;38:1637-9
114. Kaufman SC. Anterior segment complications of herpes zoster ophthalmicus. Ophthalmology 2008;115(2 Suppl):S24-32 (Pubitemid 351173971)
115. Zegans ME, Anninger W, Chapman C, Gordon SR. Ocular manifestations of hepatitisCvirus infection. Curr Opin Ophthalmol 2002;13:423-7
116. Gallar J, Morales C, Freire V, et al. Decreased corneal sensitivity and tear production in fibromyalgia. Invest Ophthalmol Vis Sci 2009;50: 4129-34
117. Blomquist PH. Ocular complications of systemic medications. Am J Med Sci 2010;342:62-9
118. Edwards RR, Calahan C, Mensing G, et al. Pain, catastrophizing, and depression in the rheumatic diseases. Nat Rev Rheumatol 2011;7: 216-24
119. Gormsen L, Rosenberg R, Bach FW, Jensen TS. Depression, anxiety, health-related quality of life and pain in patients with chronic fibromyalgia and neuropathic pain. Eur J Pain 2010;14:127.e11-8. Epub 2009 May 26
120. Elman I, Zubieta JK, Borsook D. The missing p in psychiatric training: why it is important to teach pain to psychiatrists. Arch Gen Psychiatry 2011;68:12-20
121. Apkarian AV. Pain perception in relation to emotional learning. Curr Opin Neurobiol 2008;18:464-8
122. Kim KW, Han SB, Han ER, et al. Association between depression and dry eye disease in an elderly population. Invest Ophthalmol Vis Sci 2011;52:7954-8
123. Patel VD, Watanabe JH, Strauss JA, Dubey AT. Work productivity loss in patients with dry eye disease: an online survey. Curr Med Res Opin 2011;27:1041-8
124. Cruzat A, Pavan-Langston D, Hamrah P. In vivo confocal microscopy of corneal nerves: analysis and clinical correlation. Semin Ophthalmol 2010;25(5-6):171-7
125. Magri F, Buonocore M, Oliviero A, et al. Intraepidermal nerve fiber density reduction as a marker of preclinical asymptomatic smallfiber sensory neuropathy in hypothyroid patients. Eur J Endocrinol 2010;163:279-84
126. Allgeier S, Zhivov A, Eberle F, et al. Image reconstruction of the subbasal nerve plexus with in vivo confocal microscopy. Invest Ophthalmol Vis Sci 2011;52:5022-8
127. Chapman CR. Painful multi-symptom disorders: a systems perspective. In: Kruger L, Light AR, eds. Translational Pain Research: From Mouse to Man. Boca Raton, FL, CRC Press, 2010. Chapter 1. Frontiers in Neuroscience