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Psychophysical and Neurochemical Abnormalities of Pain Processing in Fibromyalgia

Published online by Cambridge University Press:  07 November 2014

Roland Staud  and
Michael Spaeth
Roland Staud
Affiliation:
Dr. Staud is professor of medicine in the Division of Rheumatology and Clinical Immunology, McKnight Brain Institute, at the, University of Florida in Gainesville
Michael Spaeth
Affiliation:
Dr. Spaeth is medical director of the Center for Clinical Rheumatology Research in Graefelfing/Munich, Germany.
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Abstract

Fibromyalgia pain is frequent in the general population, but its pathogenesis is only partially understood. Patients with fibromyalgia lack consistent tissue abnormalities but display features of hyperalgesia (increased sensitivity to painful stimuli) and allodynia (lowered pain threshold). Many recent fibromyalgia studies have demonstrated central nervous system (CNS) pain processing abnormalities, including abnormal temporal summation of pain. In the CNS, persistent nociceptive input from peripheral tissues can lead to neuroplastic changes resulting in central sensitization and pain. This mechanism appears to represent a hallmark of fibromyalgia and many other chronic pain syndromes, including irritable bowel syndrome, temporomandibular disorder, migraine, and low back pain. Importantly, after central sensitization has been established, only minimal peripheral input is required for the maintenance of the chronic pain state. Additional factors, including pain-related negative affect and poor sleep have been shown to significantly contribute to clinical fibromyalgia pain. Better understanding of these mechanisms and their relationship to central sensitization and clinical pain will provide new approaches for the prevention and treatment of fibromyalgia and other chronic pain syndromes.

Type
Research Article
Information
CNS Spectrums , Volume 13 , Issue S5 , March 2008 , pp. 12 - 17
Copyright
Copyright © Cambridge University Press 2008

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References

1.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(11):1593–1601.CrossRefGoogle ScholarPubMed
2.Bradley, LA, Alarcon, GS, Sotolongo, A, et al.Cerebrospinal fluid (CSF) levels of substance P (SP) are abnormal in patients with fibromyalgia (FM) regardless of traumatic or insidious pain onset. Arthritis Rheum. 1998;41:256.Google Scholar
3.Vaeroy, H, Helle, R, Forre, O, Kass, E, Terenius, L. Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis. Pain. 1988;32(1):21–26.Google Scholar
4.Neeck, G. Neuroendocrine and hormonal perturbations and relations to the serotonergic system in fibromyalgia patients. Scand J Rheumatol Suppl. 2000;113:8–12.Google Scholar
5.Lautenschlager, J, Bruckle, W, Schnorrenberger, CC, Muller, W. [Measuring pressure pain of tendons and muscles in healthy probands and patients with generalized tendomyopathy (fibromyalgia syndrome)]. Z Rheumatol. 1988;47(6):397–404.Google ScholarPubMed
6.Quimby, LG, Block, SR, Gratwick, GM. Fibromyalgia: generalized pain intolerance and manifold symptom reporting. J Rheumatol. 1988;15(8):1264–1270.Google ScholarPubMed
7.Tunks, E, Crook, J, Norman, G, Kalaher, S. Tender points in fibromyalgia. Pain. 1988;34(1):11–19.Google Scholar
8.Mikkelsson, M, Latikka, P, Kautiainen, H, Isomeri, R, Isomaki, H. Muscle and bone pressure pain threshold and pain tolerance in fibromyalgia patients and controls. Arch Phys Med Rehabil. 1992;73(9):814–818.Google Scholar
9.Kosek, E, Ekholm, J, Hansson, P. Increased pressure pain sensibility in fibromyalgia patients is located deep to the skin but not restricted to muscle tissue. Pain. 1995;63(3):335–339.CrossRefGoogle Scholar
10.Crofford, LJ, Young, EA, Engleberg, NC, et al.Basal circadian and pulsatile ACTH and cortisol secretion in patients with fibromyalgia and/or chronic fatigue syndrome. Brain Behav Immun. 2004;18(4):314–325.CrossRefGoogle ScholarPubMed
11.Crofford, LJ. The hypothalamic-pituitary-adrenal axis in fibromyalgia: Where are we in 2001? J Musculoskelet Pain. 2002;10:215–220.Google Scholar
12.Bradley, LA, Sotolongo, A, Alberts, KR, et al.Abnormal regional cerebral blood flow in the caudate nucleus among fibromyalgia patients and non-patients is associated with insidious symptom onset. J Musculoskelet Pain. 1999;7:285–292.Google Scholar
13.Larson, AA, Giovengo, SL, Russell, IJ, Michalek, JE. Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways. Pain. 2000;87(2):201–211.Google Scholar
14.Giovengo, SL, Russell, IJ, Larson, AA. Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia. J Rheumatol. 1999;26(7):1564–1569.Google Scholar
15.Welin, M, Bragee, B, Nyberg, F, Kristiansson, M. Elevated substance P levels are contrasted by a decrease in met-enkephalin-arg-phe levels in CSF from fibromyalgia patients. J Musculoskelet Pain. 1995;3(suppl):4.Google Scholar
16.Bradley, LA, Alberts, KR, Alarcon, GS, et al.Abnormal brain regional cerebral blood flow (rCBF) and cerebrospinal fluid (CSF) levels of substance P (SP) in patients and non-patients with fibromyalgia (FM). Arthritis Rheum. 1996;39(suppl 19):212.Google Scholar
17.Russell, IJ. Advances in fibromyalgia: possible role for central neurochemicals. Am J Med Sci. 1998;315(6):377–384.Google Scholar
18.Almay, BG, Johansson, F, Von-Knorring, L, Le-Greves, P, Terenius, L. Substance P in CSF of patients with chronic pain syndromes. Pain. 1988;33(1):3–9.Google Scholar
19.Fischer, HP, Eich, W, Russell, IJ. A possible role for saliva as a diagnostic fluid in patients with chronic pain. Semin Arthritis Rheum. 1998;27(6):348–359.Google Scholar
20.Sjostrom, S, Tamsen, A, Hartvig, P, Folkesson, R, Terenius, L. Cerebrospinal fluid concentrations of substance P and(met)enkephalin-Arg6-Phe7 during surgery and patient-controlled analgesia. Anesth Analg. 1988;67(10):976–981.Google ScholarPubMed
21.Murphy, RM, Zemlan, FP. Differential effects of substance P on serotonin-modulated spinal nociceptive reflexes. Psychopharmacol (Berl). 1987;93(1):118–121.CrossRefGoogle ScholarPubMed
22.Schwarz, MJ, Späth, M, Müller-Bardorff, H, Pongratz, DE, Bondy, B, Ackenheil, M. Relationship of substance P, 5-hydroxyindole acetic acid and tryptophan in serum of fibromyalgia patients. Neurosci Lett. 1999;259(3):196–198.Google Scholar
23.Giovengo, SL, Russell, IJ, Larson, AA. Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia. J Rheumatol. 1999;26(7):1564–1569.Google ScholarPubMed
24.Crofford, LJ, Engleberg, NC, Demitrack, MA. Neurohormonal perturbations in fibromyalgia. Baillieres Clin Rheumatol. 1996;10(2):365–378.Google Scholar
25.Crofford, LJ, Pillemer, SR, Kalogeras, KT, et al.Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia. Arthritis Rheum. 1994;37(11):1583–1592.Google Scholar
26.Neeck, G, Crofford, LJ. Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome. Rheum Dis Clin North Am. 2000;26(4):989–1002.Google Scholar
27.Heim, C, Ehlert, U, Hellhammer, DH. The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology. 2000;25(1):1–35.Google Scholar
28.Torpy, DJ, Papanicolaou, DA, Lotsikas, AJ, Wilder, RL, Chrousos, GP, Pillemer, SR. Responses of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis to interleukin-6: A pilot study in fibromyalgia. Arthritis Rheum. 2000;43(4):872–880.Google Scholar
29.McLean, SA, Williams, DA, Stein, PK, et al.Cerebrospinal fluid corticotropin-releasing factor concentration is associated with pain but not fatigue symptoms in patients with fibromyalgia. Neuropsychopharmacology. 2006;31(12):2776–2782.Google Scholar
30.Fuller, RW. The involvement of serotonin in regulation of pituitary-adrenocortical function. Front Neuroendocrinol. 1992;13(3):250–270.Google ScholarPubMed
31.Fuller, RW. Serotonin receptors involved in regulation of pituitary-adrenocortical function in rats. Behav Brain Res. 1996;73(1-2):215–219.Google Scholar
32.Simms, RW. Fibromyalgia is not a muscle disorder. Am J Med Sci. 1998;315:346–350.Google Scholar
33.Sprott, H, Bradley, LA, Oh, SJ, et al.Immunohistochemical and molecular studies of serotonin, substance P, galanin, pituitary adenylyl cyclase-activating polypeptide, and secretoneurin in fibromyalgic muscle tissue. Arthritis Rheum. 1998;41(9):1689–1694.Google Scholar
34.Sprott, H, Salemi, S, Gay, REet al.Increased DNA fragmentation and ultrastructural changes in fibromyalgic muscle fibres. Ann Rheum Dis. 2004;63(3):245–251.Google Scholar
35.Salemi, S, Rethage, J, Wollina, U, et al.Detection of interleukin 1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha in skin of patients with fibromyalgia. J Rheumatol. 2003;30(1):146–150.Google ScholarPubMed
36.McIver, KL, Evans, C, Kraus, RM, Ispas, L, Sciotti, VM, Hickner, RC. NO-mediated alterations in skeletal muscle nutritive blood flow and lactate metabolism in fibromyalgia. Pain. 2006;120(1-2):161–169.Google Scholar
37.Graven-Nielsen, T, Arendt-Nielsen, L. Is there a relation between intramuscular hypoperfusion and chronic muscle pain? J Pain. 2002;3(4):261–263.Google Scholar
38.Elvin, A, Siosteen, AK, Nilsson, A, Kosek, E. Decreased muscle blood flow in fibromyalgia patients during standardised muscle exercise: A contrast media enhanced colour Doppler study. Eur J Pain. 2006;10(2):137–144.Google Scholar
39.Staud, R, Vierck, CJ, Robinson, ME, Price, DD. Overall fibromyalgia pain is predicted by ratings of local pain and pain related negative affect: possible role of peripheral tissues. Rheumatology (Oxford). 2006;45(11):1409–1415.Google Scholar
40.Forseth, KO, Forre, O, Gran, JT. A 5.5 year prospective study of self-reported musculoskeletal pain and of fibromyalgia in a female population: significance and natural history. Clin Rheumatol. 1999;18(2):114–121.Google Scholar
41.McBeth, J, Macfarlane, GJ, Benjamin, S, Silman, AJ. Features of somatization predict the onset of chronic widespread pain: results of a large population-based study. Arthritis Rheum. 2001;44(4):940–946.Google Scholar
42.Arnold, LM, Hudson, JI, Hess, EV, et al.Family study of fibromyalgia. Arthritis Rheum. 2004;50(3):944–952.Google Scholar
43.Thieme, K, Turk, DC, Flor, H. Comorbid depression and anxiety in fibromyalgia syndrome: relationship to somatic and psychosocial variables. Psychosom Med. 2004;66(6):837–844.Google Scholar
44.Raphael, KG, Janal, MN, Nayak, S, Schwartz, JE, Gallagher, RM. Familial aggregation of depression in fibromyalgia: a community-based test of alternate hypotheses. Pain. 2004;110(1-2):449–460.Google Scholar
45.Woolf, CJ. Windup and central sensitization are not equivalent. Pain. 1996;66(2-3):105–108.CrossRefGoogle Scholar
46.Li, J, Simone, DA, Larson, AA. Windup leads to characteristics of central sensitization. Pain. 1999;79(1):75–82.Google Scholar
47.Gracely, RH, Petzke, F, Wolf, JM, Clauw, DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 2002;46(5):1333–1343.Google Scholar
48.Staud, R, Vierck, CJ, Cannon, RL, Mauderli, AP, Price, DD. Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome. Pain. 2001;91(1-2):165–175.CrossRefGoogle ScholarPubMed
49.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.CrossRefGoogle ScholarPubMed
50.Woolf, CJ, Costigan, M. Transcriptional and posttranslational plasticity and the generation of inflammatory pain. Proc Natl Acad Sci USA. 1999;96(14):7723–7730.CrossRefGoogle ScholarPubMed
51.Staud, R, Domingo, M. Evidence for abnormal pain processing in fibromyalgia syndrome. Pain Med. 2001;2(3):208–215.Google Scholar
52.Staud, R, Domingo, M. New Insights into the pathogenesis of fibromyalgia syndrome. Med Aspects Hum Sex. 2001;1:51–57.Google Scholar
53.Vierck, CJ, Staud, R, Price, DD, et al.The effect of maximal exercise on temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome. J Pain. 2001;2(6):334–344.Google Scholar
54.Staud, R. Evidence of involvement of central neural mechanisms in generating fibromyalgia pain. Curr Rheumatol Rep. 2002;4(4):299–305.CrossRefGoogle ScholarPubMed
55.Price, DD, Staud, R, Robinson, ME, Mauderli, AP, Cannon, R, Vierck, CJ. Enhanced temporal summation of second pain and its central modulation in fibromyalgia patients. Pain. 2002;99(1-2):49–59.CrossRefGoogle ScholarPubMed
56.Staud, R, Robinson, ME, Vierck, CJ Jr, Cannon, RC, Mauderli, AP, Price, DD. Ratings of experimental pain and pain-related negative affect predict clinical pain in patients with fibromyalgia syndrome. Pain. 2003;105(1-2):215–222.CrossRefGoogle ScholarPubMed
57.Watkins, LR, Milligan, ED, Maier, SF. Glial activation: a driving force for pathological pain. Trends Neurosci. 2001;24(8):450–455.Google Scholar
58.Wieseler-Frank, J, Maier, SF, Watkins, LR. Glial activation and pathological pain. Neurochem Int. 2004;45:389–395.CrossRefGoogle ScholarPubMed
59.Wieseler-Frank, J, Maier, SF, Watkins, LR. Central proinflammatory cytokines and pain enhancement. Neurosignals. 2005;14(4):166–174.Google Scholar
60.Watkins, LR, Maier, SF. When good pain turns bad. Curr Dir Psychol Sci. 2003;12(6):232–236.Google Scholar
61.Salter, MW. Cellular signalling pathways of spinal pain neuroplasticity as targets for analgesic development. Curr Top Med Chem. 2005;5:557–567.Google Scholar
62.Cook, AJ, Woolf, CJ, Wall, PD, McMahon, SB. Dynamic receptive field plasticity in rat spinal cord dorsal horn following C-primary afferent input. Nature. 1987;325(7000):151–153.Google Scholar
63.Vierck, CJ Jr. Mechanisms underlying development of spatially distributed chronic pain (fibromyalgia). Pain. 2006;124(3):242–263.Google Scholar
64.Bazzichi, L, Giannaccini, G, Betti, Let al.Alteration of serotonin transporter density and activity in fibromyalgia. Arthritis Res Ther. 2006;8(4):R99.Google Scholar
65.Delgado, PL. Serotonin noradrenaline reuptake inhibitors: New hope for the treatment of chronic pain. Int J Psychiatr Clin Pract. 2006;10:16–21.Google Scholar