The American Journal of Medicine
Volume 123, Issue 8 , Pages 675-682 , August 2010

Pain/Depression Dyad: A Key to a Better Understanding and Treatment of Functional Somatic Syndromes

  • Don L. Goldenberg, MD

      Affiliations

    • Corresponding Author InformationRequests for reprints should be addressed to Don L. Goldenberg, MD, 2000 Washington St, Newton, MA 02462

References 

  1. Aaron LA, Buchwald D. A review of the evidence for overlap among unexplained clinical conditions. Ann Intern Med. 2001;134:868–881
  2. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the multicenter criteria committee. Arthritis Rheum. 1990;33:160–172
  3. Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology. 2006;130:480–491
  4. Kato K, Sullivan PF, Evengard B, Pedersen NL. Chronic widespread pain and its comorbidities: a population-based study. Arch Intern Med. 2006;166:1649–1654
  5. Vandvik PO, Lydersen S, Farup PG. Prevalence, comorbidity and impact of irritable bowel syndrome in Norway. Scand J Gastroenterol. 2006;41:650–656
  6. Cole JA, Rothman KJ, Cabral HJ, et al. Migraine, fibromyalgia and depression among people with IBS: a prevalence study. BMC Gastroenterol. 2006;6:26
  7. Weir PT, Harlan GA, Nkoy FL, et al. The incidence of fibromyalgia and its associated comorbidities: a population-based retrospective cohort study based on International Classification of Diseases, 9th Revision codes. J Clin Rheumatol. 2006;12:124–128
  8. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications. Gastroenterology. 2002;122:1140–1156
  9. Riedl A, Schmidtmann M, Stengel A, et al. Somatic comorbidities of irritable bowel syndrome: a systematic analysis. J Psychosom Res. 2008;64:573–582
  10. Kurland JE, Coyle WJ, Winkler A, Zable E. Prevalence of irritable bowel syndrome and depression in fibromyalgia. Dig Dis Sci. 2006;51:454–460
  11. Almansa C, Rey E, Sanchez RG, et al. Prevalence of functional gastrointestinal disorders in patients with fibromyalgia and the role of psychologic distress. Clin Gastroenterol Hepatol. 2009;7:438–445
  12. Arnold LM, Hudson JI, Keck PE, et al. Comorbidity of fibromyalgia and psychiatric disorders. J Clin Psychiatry. 2006;67:1219–1225
  13. Wojczynski MK, North KE, Pedersen NL, Sullivan PF. Irritable bowel syndrome: a co-twin analysis. Am J Gastroenterol. 2007;102:2220–2229
  14. Bair MJ, Wu J, Damush TM, et al. Association of depression and anxiety alone and in combination with chronic musculoskeletal pain in primary care patients. Psychosom Med. 2008;70:890–897
  15. Nicholl BI, Macfarlane GJ, Davies KA, et al. Premorbid psychosocial factors are associated with poor health-related quality of life in subjects with new onset of chronic widespread pain—results from the EPIFUND study. Pain. 2009;141:119–126
  16. Mussell M, Kroenke K, Spitzer RL, et al. Gastrointestinal symptoms in primary care: prevalence and association with depression and anxiety. J Psychosom Res. 2008;64:605–612
  17. Nicholl BI, Halder S, Macfarlane GJ, et al. Psychosocial risk markers for new onset irritable bowel syndrome—results of a large prospective population-based study. Pain. 2008;137:147–155
  18. Kalantar JS, Locke GR, Zinsmeister AR, et al. Familial aggregation of irritable bowel syndrome: a prospective study. Gut. 2003;52:1703–1707
  19. Bengtson M-B, Ronning T, Vatn MH, Harris JR. Irritable bowel syndrome in twins: genes and environment. Gut. 2006;55:1754–1759
  20. Kendler KS, Gatz M, Gardner CO, Pedersen NL. A Swedish national twin study of lifetime major depression. Am J Psychiatry. 2006;163:109–114
  21. Buskila D, Sarzi-Puttini P. Biology and therapy of fibromyalgia (Genetic aspects of fibromyalgia syndrome). Arthritis Res Ther. 2006;8:218
  22. Vargas-Alarcon G, Fragoso JM, Cruz-Robles D, et al. Association of adrenergic receptor gene polymorphisms with different fibromyalgia syndrome domains. Arthritis Rheum. 2009;60:2169–2173
  23. Hotoleanu C, Popp R, Trifa AP, et al. Genetic determination of irritable bowel syndrome. World J Gastroenterol. 2008;14:6636–6640
  24. Camilleri M, Andrews CN, Bharucha AE, et al. Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome. Gastroenterology. 2007;132:17–25
  25. Yu YW, Tsai SJ, Chen TJ, et al. Association study of the serotonin transporter promoter polymorphism and symptomatology and antidepressant response in major depressive disorders. Mol Psychiatry. 2002;7:1115–1119
  26. Traks T, Koido K, Eller T, et al. Polymorphisms in the interleukin-10 gene cluster are possibly involved in the increased risk for major depressive disorder. BMC Med Genetics. 2008;9:111
  27. Uceyler N, Valenza R, Stock M, et al. Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain. Arthritis Rheum. 2006;54:2656–2664
  28. Wang H, Buchner M, Moser MT, et al. The role of IL-8 in patients with fibromyalgia: a prospective longitudinal study of 6 months. Clin J Pain. 2009;25:1–4
  29. Macedo JA, Hesse J, Turner JD, et al. Adhesion molecules and cytokine expression in fibromyalgia patients: increased L-selectin on monocytes and neutrophils. J Neuroimmunolgy. 2007;188:159–166
  30. Liebregts T, Adam B, Bredack C, et al. Immune activation in patients with irritable bowel syndrome. Gastroenterology. 2007;132:913–920
  31. Dantzer R. Cytokine, sickness behavior, and depression. Immunol Allergy Clinics N Am. 2009;29:247–264
  32. Schrocksnadel K, Wirleitner B, Winkler C, Fuchs D. Monitoring tryptophan metabolism in chronic immune activation. Clin Chem Acta. 2006;364:82–90
  33. Capuron L, Ravaud A, Miller AH. Baseline mood and psychosocial characteristics of patients developing depressive symptoms during interleukin-2 and/or interferon-alpha cancer therapy. Brain Behav Immunol. 2004;18:205–213
  34. Kim YK, Na KS, Shin KH, et al. Cytokine imbalance in the pathophysiology of major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:1044–1053
  35. Alesci S, Martinez PE, Kelkar S. Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, a loss of physiological complexity in its secretion: clinical implications. J Clin Endocrinol Metab. 2005;90:2522–2530
  36. Ovaskainen Y, Koponen H, Jokelainen J, et al. Depressive symptomatology is associated with decreased interleukin-1 beta and increased interleukin-1 receptor antagonist levels in males. Psychiatry Res. 2009;167:73–79
  37. Staud R, Craggs JG, Perlstein WM, et al. Brain activity associated with slow temporal summation of C-fiber evoked pain in fibromyalgia patients and healthy controls. Eur J Pain. 2008;12:1078–1089
  38. Staud R, Robinson ME, Vierck CJ, Price DD. Diffuse noxious inhibitory controls (DNIC) attenuate temporal summation of second pain in normal males but not in normal females or fibromyalgia patients. Pain. 2003;101:167–174
  39. Jensen KB, Kosek E, Petzke F, et al. Evidence of dysfunctional pain inhibition in fibromyalgia reflected in rACC during provoked pain. Pain. 2009;144:95–100
  40. De Souza JB, Potvin S, Goffaux P, et al. The deficit of pain inhibition in fibromyalgia is more pronounced in patients with comorbid depressive symptoms. Clin J Pain. 2009;25:123–127
  41. Russell I, 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
  42. Laske C, Stransky E, Eschweiler GW, et al. Increased BDNF serum concentration in fibromyalgia with or without depression or antidepressants. J Psychiatr Res. 2007;41:600–605
  43. Wood PB, Schweinhardt P, Jaeger E, et al. Fibromyalgia patients show an abnormal dopamine response to pain. Eur J Neurosci. 2007;25:3576–3582
  44. Giesecke T, Gracely RH, Williams DA, et al. The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort. Arthritis Rheum. 2005;52:1577–1584
  45. Cook DB, Lange G, Ciccone DS, et al. Functional imaging of pain in patients with primary fibromyalgia. J Rheumatol. 2004;31:364–378
  46. Harris RE, Clauw DJ, Scott DJ, et al. Decreased central mu-opioid receptor availability in fibromyalgia. J Neurosci. 2007;27:1000–1006
  47. Harris RE, Sundgren PC, Pang Y, et al. Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia. Arthritis Rheum. 2008;58:903–907
  48. Jensen KB, Kosek E, Petzke F, et al. Evidence of dysfunctional pain inhibition in fibromyalgia reflected in rACC during provoked pain. Pain. 2009;144:95–100
  49. Zuo XL, Li YQ, Shi L, et al. Visceral hypersensitivity following cold water intake in subjects with irritable bowel syndrome. J Gastroenterol. 2006;41:311–317
  50. Wilder-Smith CH, Robert-Yap J. Abnormal endogenous pain modulation and somatic and visceral hypersensitivity in female patients with irritable bowel syndrome. World J Gastroenterol. 2007;13:3699–3704
  51. Iovino P, Tremolaterra F, Consalvo D, et al. Perception of electrocutaneous stimuli in irritable bowel syndrome. Am J Gastroenterol. 2006;101:596–603
  52. Price DD, Zhou Q, Moshiree B, et al. Peripheral and central contributions to hyperalgesia in irritable bowel syndrome. J Pain. 2006;7:529–535
  53. King CD, Wong F, Currie T, et al. Deficiency in endogenous modulation of prolonged heat pain in patients with irritable bowel syndrome and temporomandibular disorder. Pain. 2009;143:172–178
  54. Kwan CL, Diamant NE, Pope G, et al. Abnormal forebrain activity in functional bowel disorder patients with chronic pain. Neurology. 2005;65:1268–1277
  55. Bar KJ, Wagner G, Koschke M, et al. Increased prefrontal activation during pain perception in major depression. Biol Psychiatry. 2007;62:1281–1287
  56. Wagner G, Koschke M, Leuf T, et al. Reduced heat pain thresholds after sad-mood induction are associated with changes in thalamic activity. Neuropsychologia. 2009;47:980–987
  57. Hasler G, van der Veen JW, Tumonis T, et al. Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 2007;64:193–200
  58. Karege F, Vaudan G, Schwald M, et al. Neurotropin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs. Brain Res Mol Brain Res. 2005;136:29–37
  59. Kennedy SE, Koeppe RA, Young EA, Zubieta JK. Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women. Arch Gen Psychiatry. 2006;63:705–713
  60. Strigo IA, Simmons AN, Matthews SC, et al. Association of major depressive disorder with altered functional brain response during anticipation and processing of heat pain. Arch Gen Psychiatry. 2008;65:1275–1284
  61. Grimm S, Boesiger P, Beck J, et al. Altered negative BOLD responses in the default-mode network during emotion processing in depressed subjects. Neuropsychopharmacology. 2009;34:932–943
  62. Kuchinad A, Schweinhardt P, Seminowicz DA, et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?. J Neurosci. 2007;27:4004–4007
  63. Burgmer M, Gaubitz M, Konrad C, et al. Decreased gray matter volumes in the cingulo-frontal cortex and the amygdala in patients with fibromyalgia. Psychosom Med. 2009;71:566–573
  64. Videbech P, Ravnkilde B. Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry. 2004;161:1957–1966
  65. Frodl T, Koutsouleris N, Bottlender R, et al. Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression. Mol Psychiatry. 2008;13:1093–1101
  66. Zou K, Huang X, Li T, et al. Alterations of white matter integrity in adults with major depressive disorder: a magnetic resonance imaging study. J Psych Neurosci. 2008;33:525–530
  67. Hamilton JP, Siemer M, Gotlib IH. Amygdala volume in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Mol Psychiatry. 2008;13:993–1000
  68. McBeth J, Silman AJ, Gupta A, et al. Moderation of psychosocial risk factors through dysfunction of the hypothalamic-pituitary-adrenal axis in the onset of chronic widespread musculoskeletal pain. Arthritis Rheum. 2007;56:360–371
  69. Wingenfeld K, Heim C, Schmidt I, et al. HPA axis reactivity and lymphocyte glucocorticoid sensitivity in fibromyalgia syndrome and chronic pelvic pain. Psychosom Med. 2008;70:65–72
  70. Wingenfeld K, Wagner D, Schmidt I, et al. The low-dose dexamethasone suppression test in fibromyalgia. J Psychosom Res. 2007;62:85–91
  71. Dinan TG, Quigley EMM, Ahmed SMM, et al. Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker?. Gastroenterology. 2006;130:304–311
  72. Deak T, Bordner KA, McElderry NK, et al. Stress-induced increases in hypothalamic IL-1: a systematic comparison of multiple stressor paradigms. Brain Res Bull. 2005;64:541–556
  73. Merali Z, Du L, Hrdina P, et al. Dysregulation in the suicide brain: mRNA expression of corticotropin-releasing hormone receptors and GABA (A) receptor subunits in frontal cortical brain regions. J Neurosci. 2004;24:1478–1485
  74. Goldenberg DL, Burckhardt C, Crofford L. Management of fibromyalgia syndrome. JAMA. 2004;292:2388–2395
  75. Goldenberg DL. Pharmacological treatment of fibromyalgia and other chronic musculoskeletal pain. Best Pract Res Clin Rheumatol. 2007;21:499–511
  76. Uceyler N, Hauser W, Sommer C. A systematic review on the effectiveness of treatment with antidepressants in fibromyalgia syndrome. Arthritis Rheum. 2009;59:1278–1298
  77. Drossman DA, Toner BB, Whitehead WE, et al. Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders. Gastreoenterology. 2003;125:19–31
  78. Lackner JM, Jaccard J, Krasner SS, et al. Self-administered cognitive behavior therapy for moderate to severe irritable bowel syndrome: clinical efficacy, tolerability, feasibility. Clin Gastroenterol Hepatol. 2008;6:899–906
  79. Ford AC, Talley NJ, Schoenfeld PS, et al. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut. 2009;58:367–378
  80. Hudson J, Pope H. Does childhood sexual abuse cause fibromyalgia?. Arthritis Rheum. 1995;38:161–163
  81. Drossman D. Irritable bowel syndrome and sexual/physical abuse history. Eur J Gastroenterol Hepatol. 1997;9:327–330
  82. Piché M, Arsenault M, Poitras P, et al. Widespread hypersensitivity is related to altered pain inhibition processes in irritable bowel syndrome. Pain. 2010;148:49–58Epub 2009 Nov 3
  83. Giesecke T, Williams DA, Harris RE, et al. Subgrouping of fibromyalgia patients on the basis of pressure-pain thresholds and psychological factors. Arthritis Rheum. 2003;48:2916–2922

 Funding: None.

 Conflict of Interest: None of the authors have any conflicts of interest associated with the work presented in this manuscript.

 Authorship: All authors had access to the data and played a role in writing this manuscript.

PII: S0002-9343(10)00105-1

doi: 10.1016/j.amjmed.2010.01.014

The American Journal of Medicine
Volume 123, Issue 8 , Pages 675-682 , August 2010

Article Tools

* Image Usage & Resolution