Skip to main content

Advertisement

SpringerLink
Log in

Peripheral and central sensitization in fibromyalgia: Pathogenetic role

  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

Abstract

Characteristic symptoms of fibromyalgia syndrome include widespread pain, fatigue, sleep abnormalities, and distress. Patients with fibromyalgia show psychophysical evidence of mechanical, thermal, and electrical hyperalgesia. Peripheral and central abnormalities of nociception have been described in fibromyalgia. Important nociceptor systems in the skin and muscles seem to undergo profound changes in patients with fibromyalgia through unknown mechanisms. They include sensitization of vanilloid receptor, acid-sensing ion channel receptors, and purino-receptors. Tissue mediators of inflammation and nerve growth factors can excite these receptors and cause extensive changes in pain sensitivity, but patients with fibromyalgia lack consistent evidence for inflammatory soft tissue abnormalities. Therefore, recent investigations have focused on central nervous system mechanisms of pain in fibromyalgia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Treede RD, Meyer RA, Raja SN, Campbell JN: Peripheral and central mechanisms of cutaneous hyperalgesia. Prog Neurobiol 1992, 38:397–421.

    Article  PubMed  CAS  Google Scholar 

  2. Fock S, Mense S: Excitatory effects of 5-hydroxytryptamine, histamine and potassium ions on muscular group IV afferent units: a comparison with bradykinin. Brain Res 1976, 105:459–469.

    Article  PubMed  CAS  Google Scholar 

  3. Griesbacher T, Lembeck F: Effect of bradykinin antagonists on bradykinin-induced plasma extravasation, venoconstriction, prostaglandin E2 release, nociceptor stimulation and contraction of the iris sphincter muscle in the rabbit. Br J Pharmacol 1987, 92:333–340.

    PubMed  CAS  Google Scholar 

  4. Mense S: Nociception from skeletal muscle in relation to clinical muscle pain. Pain 1993, 54:241–289.

    Article  PubMed  CAS  Google Scholar 

  5. Mense S: Nociceptors in skeletal muscle and their reaction to pathological tissue changes. In Neurobiology of Nociceptors.Edited by Belmonte C, Cervero F. Oxford: Oxford Univ. Press;1996:184–201.

    Google Scholar 

  6. Schaible HG, Grubb BD: Afferent and spinal mechanisms of joint pain. Pain 1993, 55:5–54.

    Article  PubMed  CAS  Google Scholar 

  7. Barber LA, Vasko MR: Activation of protein kinase C augments peptide release from rat sensory neurons. J Neurochem 1996, 67:72–80.

    Article  PubMed  CAS  Google Scholar 

  8. Khasar SG, Ouseph AK, Chou B, et al.: Is there more than one prostaglandin E receptor subtype mediating hyperalgesia in the rat hindpaw? Neuroscience 1995, 64:1161–1165.

    Article  PubMed  CAS  Google Scholar 

  9. Abbott FV, Hong Y, Blier P: Persisting sensitization of the behavioral response to formalin-induced injury in the rat through activation of serotonin2A receptors. Neuroscience 1997, 77:575–584.

    Article  PubMed  CAS  Google Scholar 

  10. Sann H, Pierau FK: Efferent functions of C-fiber nociceptors. Z Rheumatol 1998, 57(Suppl 2):8–13.

    Article  PubMed  CAS  Google Scholar 

  11. Kitchener PD, Wilson P, Snow PJ: Selective labeling of primary sensory afferent terminals in lamina II of the dorsal horn by injection of Bandeiraea simplicifolia isolectin B4 into peripheral nerves. Neuroscience 1993, 54:545–551.

    Article  PubMed  CAS  Google Scholar 

  12. Stucky CL, Gold MS, Zhang X: Mechanisms of pain. Proc Natl Acad Sci U S A 2001, 98:11845–11846.

    Article  PubMed  CAS  Google Scholar 

  13. Caterina MJ, Julius D: The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci 2001, 24:487–517.The vanilloid receptor is essential for selective modalities of pain sensation and thermal hyperalgesia

    Article  PubMed  CAS  Google Scholar 

  14. Gunthorpe MJ, Smith GD, Davis JB, Randall AD: Characterization of a human acid-sensing ion channel (hASIC1a) endogenously expressed in HEK293 cells. Pflugers Arch 2001, 442:668–674.

    Article  PubMed  CAS  Google Scholar 

  15. Burnstock G: P2 purinoceptors: historical perspective and classification. Ciba Found Symp 1996, 198:1–28.

    PubMed  CAS  Google Scholar 

  16. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, et al.: Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 2000, 288:306–313.

    Article  PubMed  CAS  Google Scholar 

  17. Lewis T: Experiments relating to cutaneous hyperalgesia and its spread through somatic fibres. Clin Sci (Colch) 1935, 2:373–423.

    Google Scholar 

  18. Hardy JD, Wolff HG, Goodell H: Experimental evidence on the nature of cutaneous hyperalgesia. J Clin Invest 1950, 29:115–140.

    Article  PubMed  CAS  Google Scholar 

  19. Koltzenburg M: Neural mechanisms of cutaneous nociceptive pain. Clin J Pain 2000, 16:S131-S138.Primary hyperalgesia is related to changes in primary nociceptive afferents, whereas secondary hyperalgesia (increased pain sensitivity outside the area of tissue injury) critically requires functional changes in the central nervous system.

    PubMed  CAS  Google Scholar 

  20. Simms RW, Roy SH, Hrovat M, Anderson JJ, et al.: Lack of association between fibromyalgia syndrome and abnormalities in muscle energy metabolism. Arthritis Rheum 1994, 37:794–800.

    Article  PubMed  CAS  Google Scholar 

  21. De Stefano R, Selvi E, Villanova M, Frati E, et al.: Image analysis quantification of substance P immunoreactivity in the trapezius muscle of patients with fibromyalgia and myofascial pain syndrome. J Rheumatol 2000, 27:2906–2910.

    PubMed  Google Scholar 

  22. Li J, Simone DA, Larson AA: Windup leads to characteristics of central sensitization. Pain 1999, 79:75–82.

    Article  PubMed  CAS  Google Scholar 

  23. Wall PD, Woolf CJ: Muscle but not cutaneous C-afferent input produces prolonged increases in the excitability of the flexion reflex in the rat. J Physiol Lond 1984, 356:443–458.

    PubMed  CAS  Google Scholar 

  24. Schaible HG, Schmidt RF: Neurobiology of articular nociceptors. In Neurobiology of Nociceptors. Edited by Belmonte C, Cervero F. Oxford: Oxford Univ Press; 1996:202–219.

    Google Scholar 

  25. Coggeshall RE, Carlton SM: Receptor localization in the mammalian dorsal horn and primary afferent neurons. Brain Res Brain Res Rev 1997, 24:28–66.

    Article  PubMed  CAS  Google Scholar 

  26. Malcangio M, Bowery NG: GABA and its receptors in the spinal cord. Trends Pharmacol Sci 1996, 17:457–462.

    Article  PubMed  CAS  Google Scholar 

  27. Schadrack J, Zieglgansberger W: Pharmacology of pain processing systems. Z Rheumatol 1998, 57 Suppl 2:1–4.

    Article  PubMed  CAS  Google Scholar 

  28. Fields HL, Basbaum AI: Central nervous system mechanisms of pain modulation. In Textbook of Pain. Edited by Wall PD,Melzack R. Edinburgh: Churchill-Livingstone; 1994:243–257.

    Google Scholar 

  29. Mao JR: NMDA and opioid receptors: their interactions in antinociception, tolerance and neuroplasticity. Brain Res Rev 1999, 30:289–304.

    Article  PubMed  CAS  Google Scholar 

  30. Gracy KN, Svingos AL, Pickel VM: Dual ultrastructural localization of mu-opioid receptors and NMDA-type glutamate receptors in the shell of the rat nucleus accumbens. J Neurosci 1997, 17:4839–4848.

    PubMed  CAS  Google Scholar 

  31. Davidson EM, Coggeshall RE, Carlton SM: Peripheral NMDA and non-NMDA glutamate receptors contribute to nociceptive behaviors in the rat formalin test. Neuroreport 1997, 8:941–946.

    Article  PubMed  CAS  Google Scholar 

  32. Coggeshall RE, Zhou S, Carlton SM: Opioid receptors on peripheral sensory axons. Brain Res 1997, 764:126–132.

    Article  PubMed  CAS  Google Scholar 

  33. Kolesnikov Y, Pasternak GW: Topical opioids in mice: analgesia and reversal of tolerance by a topical N-methyl-Daspartate antagonist. J Pharmacol Exp Ther 1999, 290:247–252.

    PubMed  CAS  Google Scholar 

  34. Stein C, Machelska H, Binder W, Schafer M: Peripheral opioid analgesia. Curr Opin Pharmacol 2001, 1:62–65.

    Article  PubMed  CAS  Google Scholar 

  35. Hassan AH, Ableitner A, Stein C, Herz A: Inflammation of the rat paw enhances axonal transport of opioid receptors in the sciatic nerve and increases their density in the inflamed tissue. Neuroscience 1993, 55:185–195.

    Article  PubMed  CAS  Google Scholar 

  36. Chapman V, Haley JE, Dickenson AH: Electrophysiologic analysis of preemptive effects of spinal opioids on N-methyl-D-aspartate receptor-mediated events. Anesthesiology 1994, 81:1429–1435.

    Article  PubMed  CAS  Google Scholar 

  37. Sivilotti LG, Gerber G, Rawat B, Woolf CJ: Morphine selectively depresses the slowest, NMDA-independent component of C-fibre-evoked synaptic activity in the rat spinal cord in vitro. Eur J Neurosci 1995, 7:12–18.

    Article  PubMed  CAS  Google Scholar 

  38. Vaughan CW, Christie MJ: Presynaptic inhibitory action of opioids on synaptic transmission in the rat periaqueductal grey in vitro. J Physiol 1997, 498(Pt2):463–472.

    PubMed  CAS  Google Scholar 

  39. Zhang KM, Wang XM, Mokha SS: Opioids modulate N-methyl-D-aspartic acid (NMDA)-evoked responses of neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis). Brain Res 1996, 719:229–233.

    Article  PubMed  CAS  Google Scholar 

  40. Basbaum AI: Spinal mechanisms of acute and persistent pain. Reg Anesth Pain Med 1999, 24:59–67.Persistent pain should be considered a disease of the nervous system, not a symptom of a specific disease. In the setting of persistent injury, the nervous system undergoes extensive changes that exacerbate and prolong the pain condition.

    Article  PubMed  CAS  Google Scholar 

  41. Mao J, Price DD, Mayer DJ: Mechanisms of hyperalgesia and morphine tolerance: a current view of their possible interactions. Pain 1995, 62:259–274.

    Article  PubMed  CAS  Google Scholar 

  42. Coyle JT, Puttfarcken P: Oxidative stress, glutamate, and neurodegenerative disorders. Science 1993, 262:689–695.

    Article  PubMed  CAS  Google Scholar 

  43. Bliss TV, Collingridge GL: A synaptic model of memory: long-term potentiation in the hippocampus. Nature 1993, 361:31–39.

    Article  PubMed  CAS  Google Scholar 

  44. Bredt DS, Snyder SH: Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc Natl Acad Sci U S A 1989, 86:9030–9033.

    Article  PubMed  CAS  Google Scholar 

  45. Brenman JE, Bredt DS: Synaptic signaling by nitric oxide. Curr Opin Neurobiol 1997, 7:374–378.

    Article  PubMed  CAS  Google Scholar 

  46. Schuman EM, Madison DV: Nitric oxide and synaptic function. Annu Rev Neurosci 1994, 17:153–183.

    Article  PubMed  CAS  Google Scholar 

  47. Wang X, Robinson PJ: Cyclic GMP-dependent protein kinase and cellular signaling in the nervous system. J Neurochem 1997, 68:443–456.

    Article  PubMed  CAS  Google Scholar 

  48. Meller ST, Gebhart GF: Nitric oxide (NO) and nociceptive processing in the spinal cord. Pain 1993, 52:127–136.

    Article  PubMed  CAS  Google Scholar 

  49. McMahon SB, Lewin GR, Wall PD: Central hyperexcitability triggered by noxious inputs. Curr Opin Neurobiol 1993, 3:602–610.

    Article  PubMed  CAS  Google Scholar 

  50. Radhakrishnan V, Yashpal K, Hui-Chan CW, Henry JL: Implication of a nitric oxide synthase mechanism in the action of substance P: L-NAME blocks thermal hyperalgesia induced by endogenous and exogenous substance P in the rat. Eur J Neurosci 1995, 7:1920–1925.

    Article  PubMed  CAS  Google Scholar 

  51. Aimar P, Pasti L, Carmignoto G, Merighi A: Nitric oxideproducing islet cells modulate the release of sensory neuropeptides in the rat substantia gelatinosa. J Neurosci 1998, 18:10375–10388.

    PubMed  CAS  Google Scholar 

  52. Urban L, Thompson SW, Dray A: Modulation of spinal excitability: co-operation between neurokinin and excitatory amino acid neurotransmitters. Trends Neurosci 1994, 17:432–438.

    Article  PubMed  CAS  Google Scholar 

  53. Mendell LM, Wall PD: Responses of single dorsal cord cells to peripheral cutaneous unmyelinated fibres. Nature 1965, 206:97–99.

    Article  PubMed  CAS  Google Scholar 

  54. Davies SN, Lodge D: Evidence for involvement of N-methylaspartate receptors in ‘wind-up’ of class 2 neurones in the dorsal horn of the rat. Brain Res 1987, 424:402–406.

    Article  PubMed  CAS  Google Scholar 

  55. Dickenson AH, Sullivan AF: Evidence for a role of the NMDA receptor in the frequency dependent potentiation of deep rat dorsal horn nociceptive neurones following C fibre stimulation. Neuropharmacology 1987, 26:1235–1238.

    Article  PubMed  CAS  Google Scholar 

  56. Dickenson AH: A cure for wind up: NMDA receptor antagonists as potential analgesics. Trends Pharmacol Sci 1990, 11:307–309.

    Article  PubMed  CAS  Google Scholar 

  57. Price DD: Characteristics of second pain and flexion reflexes indicative of prolonged central summation. Exp Neurol 1972, 37:371–387.

    Article  PubMed  CAS  Google Scholar 

  58. Price DD, Hu JW, Dubner R, Gracely RH: Peripheral suppression of first pain and central summation of second pain evoked by noxious heat pulses. Pain 1977, 3:57–68.

    Article  PubMed  CAS  Google Scholar 

  59. Woolf CJ, Costigan M: Transcriptional and posttranslational plasticity and the generation of inflammatory pain. Proc Natl Acad Sci U S A 1999, 96:7723–7730.Pain hypersensitivity is related to early post-translational changes in the peripheral terminals of the nociceptor and in dorsal horn neurons, followed by transcription-dependent changes in effector genes (in primary sensory and dorsal horn neurons). This neuroplasticity is the result of membrane protein changes, activation of transcription factors, and altering of gene expression. Potentiation of nociceptive signals occurs as a result of the up-regulation in the dorsal root ganglion of centrally acting neuromodulators and simultaneously in the dorsal horn of the spinal cord. A-fibers can acquire the neurochemical features typical of C-fibers, enabling these fibers to induce stimulus-evoked hypersensitivity, something only C-fiber inputs normally can do.

    Article  PubMed  CAS  Google Scholar 

  60. Staud R, Vierck CJ, Cannon RL, et al.: Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome. Pain 2001, 91:165–175.Temporal summation of second pain is a C-fiber-mediated event and is relevant to pain processing. Compared with normal controls, FMS subjects were hyperalgesic and demonstrated a greater amount of temporal summation. In addition, after-sensations were greater in magnitude, lasted longer, and were frequently more painful in FMS subjects.

    Article  PubMed  CAS  Google Scholar 

  61. Vierck CJ, Staud R, Price DD, et al.: The effect of exercise on temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome. J Pain 2001, 2:334–345.Patients with FMS showed greater wind-up during heat stimuli than normal controls. Maximal exercise attenuated windup in normal control groups, but augmented it in patients with FMS. This finding suggests abnormal pain modulation in FMS.

    Article  PubMed  Google Scholar 

  62. Price DD, Staud R, Robinson ME, et al.: Enhanced temporal summation of second pain and its central modulation in fibromyalgia patients. Pain 2002, in press.

  63. Liu H, Brown JL, Jasmin L, et al.: Synaptic relationship between substance P and the substance P receptor: light and electron microscopic characterization of the mismatch between neuropeptides and their receptors. Proc Natl Acad Sci U S A 1994, 91:1009–1013.

    Article  PubMed  CAS  Google Scholar 

  64. Liu H, Wang H, Sheng M, et al.: Evidence for presynaptic N-methyl-D-aspartate autoreceptors in the spinal cord dorsal horn. Proc Natl Acad Sci U S A 1994, 91:8383–8387.

    Article  PubMed  CAS  Google Scholar 

  65. Liu H, Mantyh PW, Basbaum AI: NMDA-receptor regulation of substance P release from primary afferent nociceptors. Nature 1997, 386:721–724.

    Article  PubMed  CAS  Google Scholar 

  66. Curran T, Morgan JI: Fos: an immediate-early transcription factor in neurons. J Neurobiol 1995, 26:403–412.

    Article  PubMed  CAS  Google Scholar 

  67. Coderre TJ, Katz J, Vaccarino AL, Melzack R: Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain 1993, 52:259–285.

    Article  PubMed  CAS  Google Scholar 

  68. Tsigos C, Diemel LT, White A, et al.: Cerebrospinal fluid levels of substance P and calcitonin-gene-related peptide: correlation with sural nerve levels and neuropathic signs in sensory diabetic polyneuropathy. Clin Sci Colch 1993, 84:305–311.

    PubMed  CAS  Google Scholar 

  69. Vaeroy H, Helle R, Forre O, et al.: Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis. Pain 1988, 32:21–26.

    Article  PubMed  CAS  Google Scholar 

  70. Russell IJ, Orr MD, Littman B, et al.: Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum 1994, 37:1593–1601.

    Article  PubMed  CAS  Google Scholar 

  71. Watkins LR, Wiertelak EP, Furness LE, Maier SF: Illness-induced hyperalgesia is mediated by spinal neuropeptides and excitatory amino acids. Brain Res 1994, 664:17–24.

    Article  PubMed  CAS  Google Scholar 

  72. Mannion RJ, Costigan M, Decosterd I, et al.: Neurotrophins: peripherally and centrally acting modulators of tactile stimulus-induced inflammatory pain hypersensitivity. Proc Natl Acad Sci U S A 1999, 96:9385–9390.

    Article  PubMed  CAS  Google Scholar 

  73. Dyck PJ, Peroutka S, Rask C, et al.: Intradermal recombinant human nerve growth factor induces pressure allodynia and lowered heat-pain threshold in humans. Neurology 1997, 48:501–505.

    PubMed  CAS  Google Scholar 

  74. Petty BG, Cornblath DR, Adornato BT, et al.: The effect of systemically administered recombinant human nerve growth factor in healthy human subjects. Ann Neurol 1994, 36:244–246.

    Article  PubMed  CAS  Google Scholar 

  75. Giovengo SL, Russell IJ, Larson AA: Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia. J Rheumatol 1999, 26:1564–1569.

    PubMed  CAS  Google Scholar 

  76. Woolf CJ, Safieh-Garabedian B, Ma QP, et al.: Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity. Neuroscience 1994, 62:327–331.

    Article  PubMed  CAS  Google Scholar 

  77. Ruffolo R, Fuerstein GZ, Hunter AJ, et al.: Inflammatory cells and mediators in CNS diseases. Netherlands: Harwood Academic Press; 1999.

    Google Scholar 

  78. Watkins LR, Maier SF: Cytokines and pain: progress in inflammation research. Boston: Birkhauser; 1999.

    Google Scholar 

  79. Kreutzberg GW: Microglia: a sensor for pathological events in the CNS. Trends Neurosci 1996, 19:312–318.

    Article  PubMed  CAS  Google Scholar 

  80. Raivich G, Bluethmann H, Kreutzberg GW: Signaling molecules and neuroglial activation in the injured central nervous system. Keio J Med 1996, 45:239–247.

    PubMed  CAS  Google Scholar 

  81. Wooten MW: Function for NF-kB in neuronal survival: regulation by atypical protein kinase C. J Neurosci Res 1999, 58:607–611.

    Article  PubMed  CAS  Google Scholar 

  82. Woolf CJ, Allchorne A, Safieh-Garabedian B, Poole S: Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumour necrosis factor alpha. Br J Pharmacol 1997, 121:417–424.

    Article  PubMed  CAS  Google Scholar 

  83. Wood PL: Neuroinflammation: mechanism and management. Totowa: Humana; 2000.

    Google Scholar 

  84. Crinelli R, Antonelli A, Bianchi M, et al.: Selective inhibition of NF-kB activation and TNF-alpha production in macrophages by red blood cell-mediated delivery of dexamethasone. Blood Cells Mol Dis 2000, 26:211–222.

    Article  PubMed  CAS  Google Scholar 

  85. Johansson A, Bennett GJ: Effect of local methylprednisolone on pain in a nerve injury model. A pilot study. Reg Anesth 1997, 22:59–65.

    Article  PubMed  CAS  Google Scholar 

  86. Binder JR, Swanson SJ, Hammeke TA, et al.: Determination of language dominance using functional MRI: a comparison with the Wada test. Neurology 1996, 46:978–984.

    PubMed  CAS  Google Scholar 

  87. Hui KKS, Liu J, Makris N, et al.: Acupuncture modulates the limbic system and subcortical gray structures of the human brain: Evidence from fMRI studies in normal subjects. Hum Brain Mapp 2000, 9:13–25.

    Article  PubMed  CAS  Google Scholar 

  88. Coghill RC, Talbot JD, Evans AC, et al.: Distributed processing of pain and vibration by the human brain. J Neurosci 1994, 14:4095–4108.

    PubMed  CAS  Google Scholar 

  89. Coghill RC, Sang CN, Berman KF, et al.: Global cerebral blood flow decreases during pain. J Cereb Blood Flow Metab 1998, 18:141–147.Positron emission tomography studies have identified several brain regions activated by pain. They include the thalamus, insula, anterior cingulate cortex, and somatosensory cortex. The authors found that capsaicin-evoked pain (intradermal injection) decreased global cerebral blood flow from resting levels.

    Article  PubMed  CAS  Google Scholar 

  90. Coghill RC, Gilron I, Iadarola MJ: Hemispheric lateralization of somatosensory processing. Journal of Neurophysiology 2001, 85:2602–2612.

    PubMed  CAS  Google Scholar 

  91. Xu X, Fukuyama H, Yazawa S, et al.: Functional localization of pain perception in the human brain studied by PET. Neuroreport 1997, 8:555–559.

    Article  PubMed  CAS  Google Scholar 

  92. Jones AK, Brown WD, Friston KJ, et al.: Cortical and subcortical localization of response to pain in man using positron emission tomography. Proc R Soc Lond B Biol Sci 1991, 244:39–44.

    Article  CAS  Google Scholar 

  93. Sakiyama Y, Sato A, Senda M, et al.: Positron emission tomography reveals changes in global and regional cerebral blood flow during noxious stimulation of normal and inflamed elbow joints in anesthetized cats. Exp Brain Res 1998, 118:439–446.

    Article  PubMed  CAS  Google Scholar 

  94. Hofbauer RK, Rainville P, Duncan GH, Bushnell MC: Cortical representation of the sensory dimension of pain. Journal of Neurophysiology 2001, 86:402–411.

    PubMed  CAS  Google Scholar 

  95. Mountz JM, Bradley LA, Modell JG, et al.: Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum 1995, 38:926–938.

    Article  PubMed  CAS  Google Scholar 

  96. Kwiatek R, Barnden L, Tedman R, et al.: Regional cerebral blood flow in fibromyalgia: single-photon-emission computed tomography evidence of reduction in the pontine tegmentum and thalami. Arthritis Rheum 2000, 43:2823–2833.

    Article  PubMed  CAS  Google Scholar 

  97. Petzke F, Clauw DJ, Wolf JM, Gracely RH: Pressure pain in fibromyalgia and healthy control: Functional MRI of subjective pain experience versus objective stimulus intensity. Arthritis Rheum 2000, 43:S400.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Rheumatology and Clinical Immunology, University of Florida, PO Box 100221, 32610-0221, Gainesville, FL, USA

    Roland Staud MD & Michael L. Smitherman MD

Authors
  1. Roland Staud MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael L. Smitherman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Staud, R., Smitherman, M.L. Peripheral and central sensitization in fibromyalgia: Pathogenetic role. Current Science Inc 6, 259–266 (2002). https://doi.org/10.1007/s11916-002-0046-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11916-002-0046-1

Keywords

Search

Navigation